Prognostic and clinicopathological significance of miR-638 in cancer patients: A meta-analysis

Introduction:MiR-638 is believed to be involved in human cancers. However, the prognostic value of miR-638 in human carcinomas is controversial and inconclusive. Therefore, we conducted this meta-analysis to investigate the association between miR-638 expression and clinical outcomes in the patients with various cancers.Methods:We searched Pubmed, Embase, Wanfang, and the China National Knowledge Infrastructure (CNKI) up to September 1, 2020 to identify relevant studies. Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were used to correlate expression of miR-638 with prognosis and clinicopathological features.Results:A total of 18 studies involving 1886 patients were included in the meta-analysis. The results revealed that low miR-638 expression was significantly correlated with poor overall survival (OS) (HR = 2.09, 95% CI: 1.46–2.98, P < .001), but not with disease-free survival (DFS) (HR = 1.71, 95% CI: 0.31–9.56, P = .540). Subgroup analysis found that low miR-638 expression was associated with worse OS in patients with digestive system cancer (HR = 2.47, 95% CI: 1.85–3.30, P < .001), the reported directly from articles group (HR = 2.12, 95% CI: 1.34–3.33, P < .001), survival curves group (HR = 2.02, 95% CI: 1.07–3.80, P = .029), in studies with sample size ≥100 (HR = 2.12, 95% CI: 1.34–3.35, P = .001), and in studies with sample size <100 (HR = 2.02, 95%CI: 1.09–3.75, P = .025). Moreover, cancer patients with low miR-638 expression were prone to tumor size (OR = 1.47, 95% CI: 1.03–2.09, P = .035), earlier lymph node metastasis (present vs absent, OR = 2.26, 95% CI: 1.63–3.14, P < .001), earlier distant metastasis (present vs absent, OR = 2.60, 95% CI: 1.45–4.67, P < .001), TNM stage (III-IV vs I-II, OR = 2.01, 95% CI: 1.35–2.99, P = .001), and portal vein invasion (present vs absent, OR = 4.39, 95% CI:2.23–8.64, P < .001), but not associated with age, gender, tumor differentiation, and vascular invasion.Conclusions:MiR-638 may serve as a promising indicator in the prediction of prognosis and clinicopathological features in patients with different kinds of cancers.     

Association between Alpha B-crystallin expression and prognosis in patients with solid tumors: A protocol for systematic review and meta-analysis

Background:Alpha B-crystallin (CRYAB), as a small heat shock protein, may play critical roles in the tumorigenesis and progression of several kinds of human cancers. However, the prognostic value of CRYAB in solid malignancies remains controversial. The aim of the present study was to investigate the association between CRYAB expression and clinicopathology and prognosis of solid tumor patients.Methods:PubMed, Web of Science, EMBASE, Chinese National Knowledge Infrastructure, and WanFang databases were systematically searched to retrieve studies that investigated the prognostic value of CRYAB expression in various solid tumors. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to determine the strength of association between CRYAB expression and survival in patients with solid tumors. Odds ratios (ORs) with 95% CIs were pooled to assess the correlation between CRYAB expression and clinicopathological characteristics of patients with solid tumors.Results:A total of 17 studies, including 18 cohorts with 6000 patients, were included in this meta-analysis. Our results showed that increased CRYAB expression could predict poor overall survival (HR = 1.81, 95% CI: 1.50–2.19, P < .001), disease-free survival (HR = 1.47, 95% CI: 1.16–1.86, P = .001), and disease-specific survival (HR = 1.40, 95% CI: 1.19–1.63, P < .001) in patients with cancer. Furthermore, the high expression level of CRYAB was associated with certain phenotypes of tumor aggressiveness, such as lymph node metastasis (OR = 2.46, 95% CI: 1.48–4.11, P = .001), distant metastasis (OR = 3.34, 95% CI: 1.96–5.70, P < .001), advanced clinical stage (OR = 2.24, 95% CI: 1.24–4.08, P = .008), low OS rate (OR = 4.81, 95% CI: 2.82–8.19, P < .001), and high recurrence rate (OR = 1.38, 95% CI: 1.11–1.72, P = .004).Conclusions:CRYAB may serve as a valuable prognostic biomarker and therapeutic target in human solid tumors.     

Prognostic significance of A-kinase interacting protein 1 expression in various cancers: A meta-analysis based on the Chinese population

Background:Cumulative evidence suggests that A-kinase interacting protein 1 (AKIP1) plays an important role in tumor progression. However, the prognostic value of AKIP1 expression in various cancers remains unclear. Here, we conducted a meta-analysis to evaluate the prognostic value of AKIP1 expression in patients with cancer.Methods:The PubMed, Web of Science, EMBASE, CNKI, and Wanfang databases were systematically searched to identify studies in which the effect of AKIP1 expression on prognosis (overall survival or disease-free survival) was investigated. Hazard ratios (HRs) with 95% confidence intervals (CIs) were combined to assess the effect of AKIP1 expression on patient survival. Odds ratios (ORs) with 95% CIs were pooled to estimate the association between AKIP1 expression and clinicopathological characteristics of patients with cancer.Results:Nineteen eligible studies, encompassing 3979 patients, were included in the meta-analysis. AKIP1 expression was negatively associated with overall survival (HR = 1.86, 95% CI: 1.58–2.18, P < .001) and disease-free survival (HR = 1.69, 95% CI: 1.53–1.87, P < .001) in patients with cancer. Moreover, AKIP1 overexpression was positively correlated with adverse clinicopathological features, such as tumor size (OR = 2.22, 95% CI: 1.67–2.94, P < .001), clinical stage (OR = 2.05, 95% CI: 1.45–2.90, P < .001), depth of tumor invasion (OR = 2.98, 95% CI: 2.21–4.02, P < .001), and degree of lymph node metastasis (OR = 2.12, 95% CI: 1.75–2.57, P < .001).Conclusions:High AKIP1 expression is an unfavorable prognostic biomarker and may serve as a potential therapeutic target in patients with cancer.     

The prognostic value of lncRNA AGAP2-AS1 in cancer patients: A meta-analysis

Background:ArfGAP with GTPase domain, Ankyrin repeat and PH domain 2 Antisense 1 (AGAP2-AS1) is a promising long noncoding RNA that may possess prognostic value for different types of tumors. The objective of this meta-analysis is to evaluate the prognostic value of long noncoding RNA AGAP2-AS1 in cancer patients.Methods:A systematic literature search of the PubMed, Cochrane Library, EMBASE, Medline, Web of Science, CNKI, Weipu, and Wanfang electronic databases were carried out in this meta-analysis. Synthetic hazard ratios (HRs) or odd ratios (ORs) with 95% confidence intervals (CIs) were obtained to determine the prognostic and clinicopathological significance of AGAP2-AS1 expression in tumors.Results:The final meta-analysis included 10 studies that contained 948 patients. The pooled results provided evidence that AGAP2-AS1 overexpression predicted reduced overall survival (OS) (HR = 1.77, 95% CI: 1.49–2.09, P < .00001), disease-free survival (HR = 1.84, 95% CI: 1.40–2.41, P < .0001), and progression-free survival (HR = 1.84, 95% CI: 1.01–3.33, P = .04) and for various cancers. Additionally, the AGAP2-AS1 overexpression was concerned with lymph node metastasis (positive vs negative, OR = 2.95, 95% CI: 1.96–4.45, P < .00001), advanced tumor node metastasis stage (III/IV vs I/II, OR = 3.73, 95% CI: 2.71–5.13, P < .00001), and tumor size (larger vs smaller, OR = 2.28, 95% CI: 1.24–4.18, P = .008). Besides, data from gene expression profiling interactive analysis dataset verified the results in our meta-analysis. The results showed that the expression level of AGAP2-AS1 was higher in most tumor tissues than in the corresponding normal tissues and was linked to poor OS and disease-free survival.Conclusions:Our results indicated that AGAP2-AS1 overexpression was closely correlated with shorter OS in multiple cancer types, suggesting that AGAP2-AS1 might function as a promising predictor for clinical outcomes in cancer.     

The relationship between NLR/PLR/LMR levels and survival prognosis in patients with non-small cell lung carcinoma treated with immune checkpoint inhibitors

Background:The relationship between neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) and the dire prognosis of non-small cell lung carcinoma patients who received immune checkpoint inhibitors (ICIs) are not known yet.Methods:We screened the articles that meet the criteria from the database. The relationship between NLR/PLR/LMR levels and the survival and prognosis of non-small cell lung cancer patients treated with ICIs was analyzed. Summarize hazard ratio (HR) with 95% confidence interval (CI) to study progression-free survival (PFS) and overall survival (OS).Results:Thirty-four studies involving 3124 patients were enrolled in the final analysis. In short, high pre-treatment NLR was related to poor OS (HR = 2.13, 95% CI:1.74–2.61, P < .001, I² = 83.3%, P < .001) and PFS (HR = 1.77, 95% CI:1.44–2.17, P < .001, I² = 79.5%, P < .001). Simultaneously, high pre-treatment PLR was related to poor OS (HR = 1.49, 95% CI:1.17–1.91, P < .001, I² = 57.6%, P = .003) and PFS (HR = 1.62, 95% CI:1.38–1.89, P < .001, I² = 47.1%, P = .036). In all subgroup analysis, most subgroups showed that low LMR was related to poor OS (HR = 0.45, 95% CI: 0.34–0.59, P < .001) and PFS (HR = 0.60, 95% CI: 0.47–0.77, P < 0.001, I² = 0.0%, P < .001).Conclusion:High pre-treatment NLR and pre-treatment PLR in non-small cell lung carcinoma patients treated with ICIs are associated with low survival rates. Low pre-treatment and post-treatment LMR are also related to unsatisfactory survival outcomes. However, the significance of post-treatment NLR and post-treatment PLR deserve further prospective research to prove.     

Prognostic role of tripartite motif containing 24 in various human solid malignant neoplasms: An updated meta-analysis and systematic review

Background:Currently, clinical studies of tripartite motif containing 24 (TRIM24) on human solid malignant neoplasms were developing, but the prognosis value of TRIM24 continues to be controversial. The aim of our study is to explore the prognostic effect of TRIM24 in various human solid malignant neoplasms.Methods:We performed a comprehensive research for eligible studies which evaluated the prognostic roles of TRIM24 in cancer patients based on PubMed, Embase, Web of Science, and China National Knowledge Infrastructure. The hazard ratios (HRs) with 95% confidence intervals (CIs) for various malignances were extracted from eligible studies.Results:A total of 13 studies with 1909 patients were enrolled in this analysis. Combined analyses showed that high expression of TRIM24 significantly predicted poorer overall survival both in univariate analysis (HR = 1.61, 95% CI 1.21–2.15, P = .001) and multivariate analysis (HR = 2.19, 95% CI 1.10–4.38, P = .026). In stratified analyses, high TRIM24 expression level predicted even worse overall survival in hormone-related cancers (HR = 1.92, 95% CI 1.28–2.86, P = .001). Although, expression of TRIM24 failed to show a significant relation with progression-free survival/disease-free survival/recurrence-free survival (HR = 1.42, 95% CI 0.93–2.16, P = .106), high expression predicted significant worse progression-free survival/disease-free survival/recurrence-free survival in hormone-related cancer (HR = 1.71, 95% CI 1.12–2.59, P = .013).Conclusion:TRIM24 could serve as a new biomarker for patients with solid malignancies and could be a potential therapeutic target for patients especially for patients with hormone-related malignancies.     

High expression of HOXB7 is an unfavorable prognostic factor for solid malignancies: A meta-analysis

Background:HOXB7 is abnormally expressed in a variety of tumors, but its prognostic value remains unclear due to sample size limitation and outcome inconsistency in previous studies. This meta-analysis was performed to explore the effect of HOXB7 expression on prognoses and clinicopathological factors in range of the whole solid tumors.Methods:PubMed, EMBASE, and Web of Science databases were searched to identify included studies. Hazard ratios (HR) with its 95% confidence interval (CI) and clinicopathological factors were extracted. Subgroup analyses were performed according to histopathological type, tumor occurrence systems, and HOXB7 detection methods.Results:A total of 3430 solid tumors patients from 20 studies (21 cohorts) were included in the meta-analysis. The results showed that high HOXB7 expression was significantly associated with worse survival (overall survival: HR = 1.98, 95%CI: 1.74–2.26, P < .001 and disease-free survival: HR = 1.59, 95%CI: 1.21–2.09, P = .001), more advanced tumor-node-metastasis (TNM) stage (odds ratio [OR] = 2.14, 95%CI: 1.68–2.73, P < .001), positive lymph node metastasis (OR = 2.16, 95%CI: 1.74–2.70, P < .001), more distant metastasis (OR = 1.63, 95%CI: 1.01–2.63, P = .048), poorer differentiation (OR = 1.48, 95%CI: 1.14–1.91, P = .003), and higher Ki-67 expression (OR = 2.53, 95%CI: 1.68–3.84, P < .001). Subgroup analysis showed that survival of patients with HOXB7 high expression was worse in either squamous cell carcinomas or non-squamous cell carcinomas, digestive tumors or non-digestive tumors, and protein level or mRNA level.Conclusion:High HOXB7 expression might be a valuable biomarker of poor prognosis for solid tumors. HOXB7 promotes tumor proliferation and metastasis, and is associated with poorer differentiation, more advanced stage, even the chemotherapy resistance, suggesting that HOXB7 is a potential therapeutic target for solid tumors.     

Clinicopathological significance and prognostic value of E-cadherin expression in non-small cell lung cancer: A protocol for systematic review and meta-analysis

Background:E-cadherin, a calcium-dependent cell adhesion molecule, as an important mediator of adhesion and signaling pathway, plays a key role in maintaining tissue integrity. However, the association of E-cadherin expression with clinicopathological features and prognostic value in non-small cell lung cancer (NSCLC) is still controversial. Therefore, the purpose of the study is to explore the clinicopathological features and prognostic value of E-cadherin expression in non-small cell lung cancer by meta-analysis.Methods:PubMed, EMBASE, Cochrane Library, and Web of Science were searched to collect the studies about expression of E-cadherin and clinicopathological features and prognosis of non-small cell lung cancer. The last search time was May 2020. Stata 15.0 software was used for statistical analysis.Results:A total of 35 studies were included, of which the results showed that high expression of E-cadherin compared with its low expression, for overall survival, HR = 0.68 (95% CI:0.64–0.73, P < .05); for disease-free survival or progression-free survival, HR = 0.54 (95% CI: 0.44–0.67); low differentiation of lung cancer compared with moderate and high differentiation, OR = 0.40 (95% CI: 0.27–0.58, P < .05); Advanced lung cancer compared with early stage, OR = 0.54 (95% CI: 0.44–0.66, P < .05); lymph node metastasis compared with non-lymph node metastasis, OR = 0.49 (95% CI: 0.31∼0.77).Conclusion:Low expression of E-cadherin is closely related to poor prognosis of patients with NSCLC, promoting tumor staging and lymph node metastasis, inhibiting tumor differentiation as well.     

Anti-EGFR monoclonal antibody plus chemotherapy for treating advanced non-small cell lung cancer: A meta-analysis

Background:The use of standard cytotoxic chemotherapy seems to have reached a “treatment plateau”. The application of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) is a new strategy for non-small-cell lung cancer (NSCLC) therapy. We aimed to comprehensively assess the efficacy and safety of anti-EGFR-mAbs plus chemotherapy as first-line therapy for advanced NSCLC.Methods:According to inclusion and exclusion criteria, we conducted a comprehensive literature search of electronic databases. From the included trials, information on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) was extracted.Results:The research showed that compared with chemotherapy alone, anti-EGFR-mAb plus chemotherapy combinations significantly improved OS (HR = 0.88, 95%CI: 0.83-0.94, P < .0001), PFS (HR = 0.89, 95%CI: 0.83-0.95, P = 0.0004) and ORR (OR = 1.39, 95%CI: 1.13-1.69, P = .001). Meta subgroup analyses manifested that the OS of patients with squamous NSCLC treated with anti-EGFR-mAb plus chemotherapy combinations was notably better than that of patients with non-squamous NSCLC treated with the same combinations (HR = 0.82, 95%CI: 0.73-0.92, P = .0005). Compared with the chemotherapy group, combination of chemotherapy and anti-EGFR mAb showed increase in incidences of severe AEs (> = grade 3) that mainly include, leukopenia (OR = 1.53, 95%CI: 1.28-1.82, P < .00001), febrile neutropenia (OR = 1.35, 95%CI: 1.06-1.71, P = .02), hypomagnesemia (OR = 5.68, 95%CI: 3.54-9.10, P < .00001), acneiform rash (OR = 35.88, 95%CI: 17.37-74.10, P < .00001), fatigue (OR = 1.24, 95%CI: 1.02-1.49, P = .03), diarrhea (OR = 1.69, 95%CI: 1.16-2.47, P = .006), and infusion-related reactions (OR = 3.78, 95%CI: 1.93-7.41, P = .0001).Conclusion:Adding an anti-EGFR-mAb to the standard platinum-based chemotherapy regimens used for the first-line treatment of advanced NSCLC resulted in statistically notable improvements in OS, PFS, and ORR. In particular, anti-EGFR-mAb and chemotherapy combinations achieved greater survival benefits in patients with squamous NSCLC than in those with non-squamous NSCLC. In addition, the safety profile of chemotherapy plus anti-EGFR-mAb combinations was acceptable compared to that of chemotherapy alone.     

Prognostic significance of ANO1 expression in cancers

Background:Anoctamin-1 (ANO1) plays a pivotal role in cancer progression. A meta-analysis was conducted to assess the potential prognostic role of ANO1 in cancers.Methods:A total of 1760 patients from 7 eligible studies were included into the analysis. Pooled hazard ratios or odds ratios were extracted and calculated with a random-effects model, and analyses of heterogeneity bias were conducted.Results:Our results showed that over expression of ANO1 was significantly correlated with poor overall survival in all cancers (HR = 1.52; 95% CI: 1.19–1.92; P = .0006). Subgroup analysis indicated that there was a significant association between over expression of ANO1 and poor prognosis breast cancer (HR = 3.24; 95% CI: 1.74–6.04), head and neck squamous cell carcinoma (HR = 1.14; 95% CI: 1.00–1.30), esophageal squamous cell carcinoma (HR = 1.93; 95% CI: 1.07–3.50), gastric cancer (HR = 1.62; 95% CI: 1.12–2.34) and colorectal cancer (HR = 1.38; 95% CI: 1.03–1.85). In addition, over expression of ANO1 was not associated with TNM stage, histological grade, lymph node metastasis, tumor size, age and gender. However, ANO1 was significantly associated with human epidermal growth factor receptor 2, but not associated with progesterone receptor or estrogen receptor in breast cancer.Conclusions:Our results indicate that ANO1 can be a predictive factor for prognosis of cancer.     

Maintenance treatment of combination with bevacizumab vs single agent for advanced non-squamous non-small cell lung cancer: A systematic review and meta-analysis

Background:When the patients of advanced non-squamous non-small cell lung cancer (NSCLC) have achieved remission by induction therapy, it is controversial that combination with bevacizumab is used as maintenance therapy. Pemetrexed is a classic drug for maintenance therapy, is bevacizumab the superiority to pemetrexed is also unclear. This meta-analysis aims to evaluate the effectiveness and safety of advanced non-squamous NSCLC in the maintenance treatment.Method:From the establishment as of December 6, 2020, PubMed, Embase, and Cochrane electronic databases were searched and the American Society of Clinical Oncology, European Society of Medical Oncology, and National Comprehensive Cancer Network databases in the past 10 years. The application of combination with bevacizumab, pemetrexed was studied in clinical trials of maintenance treatment for advanced NSCLC. The extracted data include progression-free survival (PFS), overall survival (OS), and grade 3–4 adverse events (AE).Results:Seven clinical trials we screened, 6 were phase III RCTs, and a cohort trial, including 3298 patients. Compared with bevacizumab and pemetrexed, PFS of combination with bevacizumab was significantly improved (hazard ratio [HR] = 0.71, 95% confidence interval [CI] = 0.65–0.77, P < .00001), but OS was not improved (HR = 0.93, 95% CI = 0.85–1.01, P = .10). Compared with bevacizumab and pemetrexed, no significant difference of PFS (HR = 0.87, 95% CI = 0.69–1.09, P = .21), and OS (HR = 0.87, 95% CI = 0.72–1.05, P = .15) was found. A higher incidence of grade 3–4 AE occurred in combination with bevacizumab (odds ratio = 1.63, 95% CI = 1.35–1.97, P < .00001).Conclusions:PFS was significantly improved in patients with advanced non-squamous NSCLC who use bevacizumab combination with single-agent as maintenance treatment, but it does not translate into the advantages of OS; compared with bevacizumab, no PFS and OS benefits were found. A higher incidence of grade 3–4 AE occurred in combination with bevacizumab than pemetrexed and bevacizumab.     

Prognostic value of HHLA2 expression in solid tumors: A meta-analysis based on the Chinese population

Background:Human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2), a newly discovered member of the B7 family, is overexpressed in numerous tumors. However, the prognostic impact of HHLA2 in human cancers remains controversial. Thus, we performed this meta-analysis to explore the prognostic value of HHLA2 in Chinese patients with solid tumors.Methods:PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, and WanFang databases were systematically searched for eligible studies that evaluated the impact of HHLA2 on overall survival (OS) in patients with cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) were combined to evaluate the association between HHLA2 expression and OS in solid tumors. Odds ratios (ORs) and 95% CIs were pooled to assess the correlation between HHLA2 expression and clinicopathological characteristics in solid tumors.Results:A total of 12 studies, including 15 cohorts and 1747 patients, were included in this meta-analysis. We found that high HHLA2 expression was significantly associated with shorter OS (HR = 1.65, 95% CI: 1.12–2.43). Subgroup analysis by cancer type demonstrated that high HHLA2 expression was associated with poor OS in patients with clear cell renal cell carcinoma (HR = 3.42, 95% CI: 2.39–4.91), gastric cancer (HR = 2.03, 95% CI: 1.31–3.16), intrahepatic cholangiocarcinoma (HR = 1.77, 95% CI: 1.24–2.53), lung cancer (HR = 2.14, 95% CI: 1.33–3.44) and other cancer types (HR = 2.08, 95% CI: 1.34–3.24), but not in patients with epithelial ovarian cancer (HR = 0.52, 95% CI: 0.08–3.56). Nevertheless, high HHLA2 expression was associated with better OS in patients with pancreatic ductal adenocarcinoma (HR = 0.45, 95% CI: 0.32–0.64). Furthermore, high HHLA2 expression was associated with old age (OR = 1.30, 95% CI: 1.03–1.63), lymph node metastasis (OR = 1.99, 95% CI: 1.41–2.81), and vascular invasion (OR = 1.69, 95% CI: 1.18–2.42).Conclusions:HHLA2 may serve as a potential prognostic biomarker for solid tumors in Chinese population, by predict the prognosis of cancer patients based on their tumor types.     

Efficacy and safety of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitor versus chemotherapy for advanced lung cancer: A meta-analysis

Background:This meta-analysis was performed to compare efficacy and tolerability between antiprogrammed cell death (PD-1)/programmed cell death-ligand-1 (PD-L1) + anticytotoxic T-lymphocyte-associated protein-4 (CTLA-4) treatment and chemotherapy in advanced lung cancer.Methods:Cochrane Library, Embase, and PubMed databases were searched for potential articles. The fixed-effect model or random-effect model was adopted for pooled analysis based on the I² and P-value.Results:Six articles with 1338 patients were identified and subjected to meta-analysis. Compared with chemotherapy, anti-PD-1/PD-L1 + anti-CTLA-4 treatment could significantly improve the overall survival (hazard ratio [HR] = 0.78, 95%confidence interval [CI]: 0.71–0.84, P = .21) and progression-free survival (HR = 0.77, 95%CI: 0.71–0.83, P = .30) of advanced lung cancer patients. Moreover, there was no obvious difference in the incidence of 3 to 4 adverse events (AEs) serious adverse reactions (HR = 1.35, 95%CI: 0.66–2.74, P < .00001) between the 2 treatment groups, but the incidence rates of AEs leading to discontinuation (HR = 2.56, 95%CI: 1.53–4.30, P < .00001) and AEs leading to death (HR = 2.10, 95%CI: 1.21–3.63, P = .20) were higher. Furthermore, no remarkable differences in objective response rate (HR = 1.31, 95%CI: 0.97–1.77, P = .02) were observed between the 2 groups.Conclusion:Our meta-analysis revealed that PD-1/PD-L1 inhibitors plus CTLA-4 inhibitor could markedly improve the endpoint outcomes of patients compared with chemotherapy alone, and did not significantly increase the serious adverse reactions. Thus, it can serve as a new treatment strategy for advanced lung cancer.     

The high expression of CHD1L and its clinical significance in human solid tumors: A meta-analysis

Background:Chromodomain helicase DNA-binding protein 1-like (CHD1L) is an oncogene. It was cloned from 1q21 chromosome region of hepatocellular carcinoma in 1991. CHD1L is up-regulated in many kinds of cancers and is involved in the carcinogenesis and development of tumors. More and more studies have shown that over-expression of CHD1L is associated with poor prognosis of tumors. The purpose of this study was to evaluate the prognostic value of CHD1L in human solid tumors.Methods:The key words in the database of PubMed, Web of Science, Embase, Cochrane library, and TCGA were searched for systematic literature retrieval. We collected relevant articles and data about CHD1L and prognosis of cancer and screened them according to the eligible criteria to evaluate the prognostic value of CHD1L in cancer patients. Then Stata SE12.0 software is used to analyze the data.Results:In our meta-analysis, 2720 patients with a total of 15 articles involving multiple types of tumors showed that high expression levels of CHD1L were associated with shorter overall survival (OS) (hazard ratio  = 2.21, 95% confidence interval [CI]: (1.49–3.30)] and (hazard ratio  = 1.16, 95% CI: (1.01–1.32)] in the TCGA database, in addition, the pooled odds ratios (ORs) indicated high expression levels of CHD1L in tumors significantly are associated with TNM stage (OR = 1.61, 95% CI: 1.01–2.55, P < .05), tumor size (OR = 1.38, 95% CI: 1.07–1.78, P < .05), tumor differentiation (OR = 2.13, 95% CI: 1.43–3.16, P < .05), and distant metastasis (OR = 1.86, 95% CI: 1.45–2.39 P < .05). However, we did not observe a significant correlation between the high expression of CHD1L and age, gender.Conclusion:The high expression of CHD1L is associated with poor OS as well as related to tumor differentiation, tumor size, and distant metastasis, which can be served as a prognostic marker and a potential predictor of clinical pathology in human solid tumors.     

Prognostic value of EGFR and p-EGFR in nasopharyngeal carcinoma: A systematic review and meta-analysis

Purpose:To evaluate the prognostic effect and clinical significance of epidermal growth factor receptor and its phosphorlated form (EGFR/p-EGFR) in nasopharyngeal carcinoma.Methods:A systematic review and meta-analysis was designed. We visited PubMed, Embase, China National Knowledge Infrastructure Database, Database of Chinese sci-tech periodicals, WanFang Database, and China Biology Medicine disc to search for Chinese and English publications of prospective studies and retrospective studies investigating the association of EGFR/p-EGFR and nasopharyngeal carcinoma prognosis from inception to April 2021. The inclusion criteria were that the samples should be pathologically confirmed as nasopharyngeal carcinoma and the expression of EGFR/p-EGFR should be detected via immunohistochemistry; the study should analyze the prognostic significance of EGFR/p-EGFR in nasopharyngeal carcinoma; hazard ratio (HR) and 95% confidence interval (CI) should be reported in the study or could be derived from survival curves; and the outcomes of the study should include overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS).Results:A total of 18 studies evaluating 1451 samples were included. For studies that reported OS as an outcome, EGFR overexpression indicated worse OS of nasopharyngeal carcinoma patients. The heterogeneity between studies was high (I² = 91%, P < .01), and a random-effect model was used to combine the effect size (HR = 1.71, 95% CI [1.21, 2.41], P < .01). Further sensitivity analysis and prespecified subgroup analysis were performed to detect the source of heterogeneity, and the results showed that the heterogeneity could not be eliminated. Publication bias assessed by funnel plots and Begg test and Egger test was low (Begg test: P = .846 and Egger test: P = .074). p-EGFR was not correlated with the OS of nasopharyngeal carcinoma patients (HR = 1.01, 95% CI [0.88, 1.15], P = .92). For studies that reported DFS, EGFR overexpression was associated with worse DFS in patients with nasopharyngeal carcinoma (HR = 2.53, 95% CI [1.84, 3.47], P < .01). For studies that reported PFS, EGFR overexpression was not correlated with the PFS of nasopharyngeal carcinoma patients (HR = 1.86, 95% CI [0.90, 3.82], P = .09). For studies that reported DMFS, EGFR overexpression was not correlated with the DMFS of nasopharyngeal carcinoma patients, and high heterogeneity between studies was detected (I² = 97%, P < .01). A random-effect model was used to combine the effect size (HR = 1.80, 95% CI [0.56, 5.76], P = .32). A sensitivity analysis was conducted. Publication bias was detected to be low (Begg test: P = .817 and Egger test: P = .954). There was no correlation between p-EGFR overexpression and DMFS in patients with nasopharyngeal carcinoma (HR = 1.20, 95% CI [0.95, 1.52], P = .12).Conclusion:In nasopharyngeal carcinoma patients, EGFR overexpression could be used as a biomarker that predicts poor OS and DFS, but not a prognostic biomarker for PFS and DMFS. The overexpression of p-EGFR was not shown to be associated with the prognosis of nasopharyngeal carcinoma patients and could not be used as a prognostic biomarker.Ethics and dissemination:This study was registered on the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), and reported as stated by the Preferred Reporting Items for Systematic reviews and Meta-Analyses. Neither ethical approval nor informed consent was required since this study was conducted based on previous publications.INPLASY registration number:INPLASY 202150010     

Anlotinib,a novel TKI,as a third-line or further-line treatment in patients with advanced non-small cell lung cancer in China: A systemic review and meta-analysis of its efficacy and safety

Purpose:In this meta-analysis and systemic review, we focused on the effectiveness and safety of anlotinib in patients with advanced non-small cell lung cancer(NSCLC).Methods:The databases of PubMed, EMBASE, Cochrane Library, CNKI, Wanfang, and CBM were searched by 2 investigators up to April 2020. Titles and abstracts of all records were screened and eligible publications were retrieved in full. Review Manager (version 5.2, Cochrane Library) was used for data analysis. The outcomes of interest were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse event (TRAE). Data was pooled for quantitative analysis and the effect size was reported as hazard ratio for survival outcomes and odds ratio (OR) for safety outcomes, both with a random-effects model.Results:A sum of 1480 patients were included in 11 trials ranging from 2018 to 2020. Substantial improvements of PFS, OS, and DCR were observed in patients treated with anlotinib alone or in combination with other conventional treatment. Accompanied TRAE included statistically significant higher risk for hypertension (OR = 11.05, 95% confidence interval [CI] = 7.85–15.55, P < .001), hepatic dysfunction (OR = 1.96, 95% CI = 1.29–2.68, P < .001), diarrhea (OR = 2.20, 95% CI = 1.17–4.16, P < .05), and hemoptysis (OR = 2.59, 95% CI = 1.71–3.93, P < .01).Conclusions:Our study suggested that anlotinib as maintenance therapy for advanced NSCLC patients is associated with prolonged PFS and OS as well as DCR improvement, but it was accompanied by increased risk of TRAE, such as hypertension, hepatic dysfunction, diarrhea and hemoptysis. Although much effort has been made to clinical trials of anlotinib, further studies are warranted to provide more convincing evidence.     

Overexpression of macrophage-colony stimulating factor-1 receptor as a prognostic factor for survival in cancer: A systematic review and meta-analysis

Background:The relation between the expression of macrophage-colony stimulating factor-1 receptor (CSF-1R) and prognosis of cancer patients has been evaluated in multiple studies, but the results remain controversial. We, therefore, performed a meta-analysis and systematic review to figure out the role of CSF-1R in the prognosis of patients with cancer.Methods:Several databases were searched, including Web of Science, PubMed, and EMBASE. All human studies were published as full text. The Newcastle–Ottawa risk of bias scale was applied to evaluate the research. We extracted hazard ratios (HRs) with 95% confidence interval (95% CI) which assessed progression-free survival (PFS) and overall survival (OS) in order to assess the impacts of CSF-1R on the prognosis of cancer patients.Results:A total of 12 citations were identified, with studies including 2260 patients in different cancer types that met the eligibility criteria. It was suggested in a pooled analysis that the over-expression of CSF-1R was significantly related to worse PFS (HR: 1.68; P < .001, 1.25–2.10, 95% CI) and also poorer OS (HR=1.28; P < .001, 1.03–1.54, 95% CI). Analysis in subgroups indicated over-expressed CSF-1R was significantly associated with worse OS in hematological malignancy (HR = 2.29; P < .001, 1.49–3.09, 95% CI; model of fixed-effects; I² = 0.0%, P < .001). Sensitivity analysis suggested that there was no study influencing the stability of the results.Conclusions:The overexpression of CSF-1R was significantly predictive of worse prognosis in those who suffer from different kinds of malignancies, particularly in hematological malignancy, which indicates that it might be a potential biomarker of prognosis in cancer survival and a potential molecular target in the treatment of malignant tumors.     

Prognostic Value of Plasma Epstein–Barr Virus DNA for Local and Regionally Advanced Nasopharyngeal Carcinoma Treated With Cisplatin-Based Concurrent Chemoradiotherapy in Intensity-Modulated Radiotherapy Era

This study aimed to evaluate the prognostic value of plasma Epstein–Barr Virus DNA (EBV DNA) for local and regionally advanced nasopharyngeal carcinoma (NPC) patients treated with concurrent chemoradiotherapy in intensity-modulated radiotherapy (IMRT) era.In this observational study, 404 nonmetastatic local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy were recruited. Blood samples were collected before treatment for examination of plasma EBV DNA levels. We evaluated the association of pretreatment plasma EBV DNA levels with progression-free survival rate (PFS), distant metastasis-free survival rate (DMFS), and overall survival rate (OS).Compared to patients with an EBV DNA level <4000 copies/mL, patients with an EBV DNA ≥4000 copies/mL had a lower rate of 3-year PFS (76%, 95% CI [68–84]) versus (93%, 95% CI [90–96], P < 0.001), DMFS (83%, 95% CI [76–89]) versus (97%, 95% CI [94–99], P < 0.001), and OS (85%, 95% CI [78–92]) versus (98%, 95% CI [95–100], P < 0.001). Multivariate analysis showed that pretreatment EBV DNA levels (HR = 3.324, 95% CI, 1.80–6.138, P < 0.001) and clinical stage (HR = 1.878, 95% CI, 1.036–3.404, P = 0.038) were the only independent factor associated with PFS, pretreatment EBV DNA level was the only significant factor to predict DMFS (HR = 6.292, 95% CI, 2.647–14.956, P < 0.001), and pretreatment EBV DNA levels (HR = 3.753, 95% CI, 1.701–8.284, P < 0.001) and clinical stage (HR = 2.577, 95% CI, 1.252–5.050, P = 0.010) were significantly associated with OS. In subgroup analysis, higher plasma EBV DNA levels still predicted a worse PFS, DMFS, and OS for the patients stage III or stage IVa-b, compared with those with low EBV DNA levels.Elevated plasma EBV DNA was still effective prognostic biomarker for local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy. Future ramdomized clinical trials are needed to further evaluate whether plasma EBV DNA levels could be applied to guide concurrent chemotherapy regimen for local and regionally advanced NPC patients.     

Prognostic significance of the expression of metastasis-associated in colon cancer-1 in gynecologic cancers and breast cancer: A protocol for systematic review and meta-analysis

Background:The prognostic role of the expression of metastasis-associated in colon cancer-1 (MACC1) in gynecologic cancers and breast cancer remains unclear. The aim of this systematic review and meta-analysis was to determine the prognostic significance of MACC1 expression in gynecologic cancers and breast cancer.Materials and methods:PubMed, Web of Science and Embase were comprehensively searched up to February 9, 2020. Studies focusing on the relationship between the expression of MACC1 and prognosis in gynecologic cancers and breast cancer were included into the analysis. Pooled hazard ratio (HR) or odd ratio with 95% confidence interval (CI) was used to estimate the prognostic value of the expression of MACC1.Results:A total of 1,811patients with gynecologic cancers or breast cancer were included into the analysis. Patients with high expression of MACC1 tended to suffer a shorter overall survival (HR = 2.76, 95%CI = 2.12–3.59, P < .01) and recurrence-free survival (HR = 2.37, 95%CI = 1.44–3.90, P < .01) compared to those with low expression of MACC1. High expression of MACC1 was significantly associated with worse tumor differentiation (P = .04), more advanced FIGO stage (P < .01) and earlier lymph node metastasis (P < .01) compared to low expression of MACC1.Conclusion:Compared to low expression of MACC1, high expression of MACC1 predicts a worse prognosis of gynecologic cancers and breast cancer. The expression of MACC1 can serve as a prognostic indicator of gynecologic cancers and breast cancer.