PAK4 expression is associated with the prognosis in non-small cell lung cancer

This study attempted to determine the expression of p21-activated kinase 4 (PAK4) in non-small cell lung cancer (NSCLC) tissues and the normal lung tissues. The correlation between PAK4 expression and prognosis of NSCLC patients was also evaluated in the present study. The expression level of PAK4 was measured by high-performance liquid chromatography method. Chi-square test was adopted to explore the relationship of PAK4 expression and clinical features. Kaplan-Meier survival curves were plotted to delineate the overall survival rate of NSCLC patients. Cox regression analysis was performed to evaluate the prognostic significance of PAK4 expression in NSCLC. The PAK4 expression in NSCLC tissue samples was significantly higher than that in normal lung tissues (P<0.001) and shared significant correlation with Eastern Cooperative Oncology Group score, histological type, and distant metastasis (P<0.05). Survival curve revealed that NSCLC patients with high PAK4 expression had relatively higher mortality than those with low PAK4 expression (P = .001). Cox regression analysis explained that PAK4 expression was associated with the prognosis of NSCLC patients (P = .024; HR, 3.104; 95% CI, 1.164–8.278). In a word, PAK4 was highly expressed in NSCLC tissues and could act as a prognostic factor for NSCLC patients.     

LKB1 expression and the prognosis of lung cancer: A meta-analysis

Background:In the past few decades, many lines of evidence implicate the importance of liver kinase B1 (LKB1) as a tumor suppressor gene in the development and progression of solid tumours. However, the prognostic and clinicopathological value of LKB1 in patients with lung cancer are controversial. This article aimed to investigate the latest evidence on this question.Methods:A systematic literature searched in the PubMed, Web of Science, Embase, Cochrane library, Scopus until September 20, 2020. The association between overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS), clinicopathological features and LKB1 were analysed by meta-analysis.Results:Eleven studies including 1507 patients were included in this meta-analysis. The pooled results revealed that low LKB1 expression was significantly associated with poor overall survival (OS) (HR = 1.67, 95% CI: 1.07–2.60, P = .024) in lung cancer. However, no association was found between LKB1 expression and DFS/PFS (HR = 1.29, 95% CI: 0.70–2.39, P = .410). Pooled results showed that low LKB1 expression was associated with histological differentiation (poor vs moderate or well, OR = 4.135, 95% CI:2.524–6.774, P < .001), nodal metastasis (absent vs present, OR = 0.503, 95% CI: 0.303–0.835, P = .008) and smoking (yes vs no, OR = 1.765, 95% CI: 1.120–2.782, P = .014).Conclusion:These results suggest that low expression of LKB1 can be considered as a unfavorable prognostic biomarker for human lung cancer, which should be further researched.     

Expression of miR-92a is associated with the prognosis in non-small cell lung cancer: An observation study

With the development of molecular biology technology, the discovery of microRNAs (miRNAs) has provided new ideas for the diagnosis, treatment, and prognosis of lung cancer and laid a foundation for the study of this malignancy. To assess the potential prognostic value of miR-92a as a new biomarker in non-small cell lung cancer (NSCLC) via clinical evaluation, a total of 100 patients with NSCLC admitted to the Respiratory and Intensive Care Department of Suining Central Hospital in Sichuan Province between August 2007 and April 2020 were retrospectively analyzed. The correlation between miR-92a expression and prognosis of patients with NSCLC was also evaluated in the present study. The expression level of miR-92a was measured by PT-PCR and in situ hybridization. Chi-square test was adopted to explore the relationship of miR-92a expression and clinical features. Kaplan–Meier survival curves were plotted to delineate the overall survival rate of patients with NSCLC. Cox regression analysis was performed to evaluate the prognostic significance of miR-92a expression in NSCLC. The miR-92a expression in NSCLC tissue samples was significantly higher than that in normal lung tissues (P < .001) and significantly correlated with the Eastern Cooperative Oncology Group score, histological type, and distant metastasis (P < .05). Survival curve revealed that patients with NSCLC and high miR-92a expression had relatively higher mortality than those with low PAK4 expression (P = .001). Cox regression analysis explained that miR-92a expression was associated with the prognosis of patients with NSCLC (HR = 1.8, 95% CI: 1.0–3.2, P = .036). In summary, miR-92a was highly expressed in NSCLC tissues and could act as a prognostic factor for patients with NSCLC. These results illustrate that miR-92a expression plays an important role in the invasion and metastasis of NSCLC, and miR-92a can be used as a new biomarker to determine the prognosis of this cancer.     

Prognostic value of symptoms at lung cancer diagnosis: a three-year observational study

BackgroundLung cancer is mainly diagnosed at advanced or locally advanced stages, usually when symptoms become evident. However, sometimes it may be diagnosed incidentally during routine care, while patients are still asymptomatic. Prognosis differences based on symptomatic presentation have been partially explored. Our aim was to analyze the prognostic value of the initial symptomatic state of the patients in a general lung cancer cohort.MethodsObservational ambispective study including patients consecutively diagnosed with primary lung cancer between January 2016 and December 2018 via the lung cancer Fast Diagnostic Track (FDT). Patients were followed up until death or the end of the study in September 2019. Asymptomatic patients were compared with patients presenting symptoms. Overall survival (OS) of both groups was compared using the log-rank test. Cox regression analysis was performed to clarify the effect of the symptomatic status at diagnosis on survival. Additionally, propensity score (PS) matching analysis was performed.ResultsA total of 267 patients were analyzed; 83.5% were men, with a mean (SD) age at diagnosis of 68 (10.7) years. Incidental diagnosis was ascertained in 24.7% of cases. Asymptomatic patients presented more frequently stage I and II disease compared to symptomatic patients (51.5% vs. 14%), and exhibited a significantly better prognosis, with a 3-year OS of 63.6% (vs. 30.3%) and a median OS that was not reached during follow-up (vs. 10.3 months). With an adjusted multivariate Cox proportional hazard model, we obtained a HR (95% CI) of 2.63 (95% CI, 1.6–4.2; P<0.0001) associated with symptomatic presentation independently of age, sex, stage at diagnosis and ECOG scale. In addition, after performing the propensity score matching analysis, the Cox regression model continued to show a significantly worse prognosis for patients presenting with symptoms (P=0.041).ConclusionsLung cancer patients who are asymptomatic at diagnosis exhibit a significantly better prognosis, regardless of the stage of the disease, underlining the importance of an early diagnosis.     

Elevated platelet count is a strong predictor of poor prognosis in stage I non-small cell lung cancer patients

Stage I non-small cell lung cancer (NSCLC) show a highly variable biological behavior which cannot be accurately predicted by the current available prognostic markers. Platelet plays a significant role in cancer cell growth, progression and metastasis. This study aimed to investigate whether preoperative platelet count correlate with clinical prognosis in localized NSCLC. A retrospective clinical analysis was designed for a total of 234 stage I NSCLC patients in our hospital between October 2006 and December 2009. Pre-operative platelet count was measured. The association of platelet count with clinical pathological factors and patient outcome was evaluated. A significant correlation was detected between platelet count and tumor cell differentiation and T stage. Patients with elevated platelet count had an elevated risk of disease progression and death compared to patients with normal platelet count. The hazard ratio was 5.314 (95% confidence interval [CI] 2.750–10.269) for disease progression and 3.139 (95% CI 1.227–8.034) for death. The trend linking increasing platelet count with risk was also statistically significant for both the outcomes (p?<?0.05). These finding demonstrate that preoperative platelet count is a useful predictor of high risk progression and poor prognosis in stage I NSCLC patients.     

有肺癌家族史的非小细胞肺癌患者的临床病理特征及预后

目的分析有明确肺癌家族史(FHLC)的非小细胞肺癌(NSCLC)患者的临床病理特征及预后。方法对浦东新区陆家嘴社区卫生服务中心登记的NSCLC切除术后患者的临床病理特征及预后进行分析。结果在428例NSCLC患者中,51例有FHLC。手术患者中早期肺癌的比例在FHLC和非FHLC患者中均较高。FHLC组的肺癌更多的为早期肺癌(P=0.037),且病理类型多为腺癌(P=0.018)。FHLC患者的死亡危险比为0.775(95%CI:0.534-1.275,P=0.327)。结论有FHLC的NSCLC患者具有病理早期和腺癌为主的特点,但其死亡危险比并未减少。     

Short-and long-term outcomes following laparoscopic vs open surgery for pathological T4 colorectal cancer: 10 years of experience in a single center

AIM To evaluate the short-term and long-term outcomes following laparoscopic vs open surgery for pathological T4(pT 4) colorectal cancer.METHODS We retrospectively analyzed the short-and long-term outcomes of proven p T4 colorectal cancer patients who underwent complete resection by laparoscopic or open surgery from 2006 to 2015 at Guangdong General Hospital.RESULTS A total of 211 p T4 colorectal cancer patients were included in this analysis, including 101 cases in thelaparoscopy(LAP) group and 110 cases in the open surgery(OPEN) group [including 15(12.9%) cases of conversion to open surgery]. Clinical information(age, gender, body mass index, comorbidities, American Society of Anesthesiologists score, etc.) did not differ between the two groups. In terms of blood loss, postoperative complications and rate of recovery, the LAP group performed significantly more favorably(P 0.05). With regard to p T4 a/b and combined organ resection, there were significantly more cases in the OPEN group(P 0.05). The 3-and 5-year overall survival rates were 74.9% and 60.5%, respectively, for the LAP group and 62.4% and 46.5%, respectively, for the OPEN group(P = 0.060). The 3-and 5-year disease-free survival rates were 68.0% and 57.3%, respectively, for the LAP group and 55.8% and 39.8%, respectively, for the OPEN group(P = 0.053). Multivariate analysis showed that ⅢB/ⅢC stage, lymph node status, and CA19-9 were significant predictors of overall survival. PT4 a/b, ⅢC stage, histological subtypes, CA19-9, and adjuvant chemotherapy were independent factors affecting disease-free survival.CONCLUSION Laparoscopy is safely used in the treatment of p T4 colorectal cancer while offering advantages of minimal invasiveness and faster recovery. Laparoscopy is able to achieve good oncologic outcomes similar to those of open surgery. We recommend that laparoscopy be carried out in experienced centers. It is still required to screen the appropriate cases for laparoscopic surgery, optimize the preoperative diagnosis process, and reduce the conversion rate. Multi-center, prospective, and large-sample studies are required to assess these issues.     

淋巴管内皮透明质酸受体1对肺癌转移及预后评价的意义研究

目的检测肺癌患者血清淋巴管内皮透明质酸受体1(LYVE-1)水平,并探讨血清LYVE-1用于判断肺癌患者是否发生淋巴结转移及预测患者预后的临床意义。方法采用酶联免疫法(ELISA)检测57例肺癌患者血清中LYVE-1的水平,同时分析血清LYVE-1水平与患者临床病理特征的关系,通过受试者工作曲线(ROC)分析血清LYVE-1用于判断肺癌患者是否发生淋巴结转移的可行性,Kaplan-Meier法进行生存分析,评价LYVE-1用于预测病人预后的临床意义。结果肺癌患者血清LYVE-1为1625.0±343.0 pg/m L;血清LYVE-1与肺癌患者性别、肿瘤组织学分型、血清CEA和CA125无统计学差异(P0.05),而与TNM分期、淋巴结转移和远处转移情况有关(P0.05);血清LYVE-1用于诊断肺癌患者发生淋巴结转移的曲线下面积为0.728(95%CI:0.685-0.747,P0.05);LYVE-1的为1821 pg/m L时,其诊断的敏感性为79%,特异性为68%;血清LYVE-1大于1821pg/m L的肺癌患者预后要比血清LYVE-1小于1821 pg/m L的肺癌患者预后差,两组总生存时间有统计学差异(P=0.035)。结论血清LYVE-1可用于确定肺癌患者是否发生淋巴结转移,并可用于评估病人预后。     

Association of ERBB4 genetic polymorphism with the risk and prognosis of non-small cell lung cancer in Chinese Han population: A population-based case–control study

The aim of this study was to explore the association of rs1836724 single-nucleotide polymorphism (SNP) of ERBB4 with risk and prognosis of non-small cell lung cancer (NSCLC) in the Chinese Han population.The genotype of rs1836724 SNP of ERBB4 from 258 patients with NSCLC and 200 noncancer controls were detected the TaqMan-MGB probes real-time fluorescence polymerase chain reaction. The distribution of genotype and alleles between the 2 groups was compared, and the association between clinicopathological characteristic and rs1836724 SNP was analyzed. Prognosis and influencing factors were analyzed by Kaplan-Meier and Cox regression analysis.There were significant differences in the genotype and allele distribution of ERBB4 rs1836724 between the NSCLC group and control group (P < .05). And CC genotype of rs1836724 was associated with increased risk of NSCLC in the Chinese Han population. Rs1836724 SNP was associated with TNM stage and lymph nodal metastasis (P = .001, P = .007). The median follow-up was 29 months, and the progression-free survival and overall survival of 258 NSCLC patients were 27.91% and 31.39%, respectively. Patients with GG genotype of rs1836724 had poor progression-free survival and overall survival. Rs1836724 SNP was an independent prognostic marker of NSCLC patients, CC genotype had a high risk of poor prognosis (odds ratio = 1.587, 95% confidence interval: 1.079–2.335, P = .019).In Chinese Han populations, rs1836724 SNP of ERBB4 may contribute toward the increased risk and poor prognosis of NSCLC.     

Prognostic value of FGFR1 gene copy number in patients with non-small cell lung cancer: a meta-analysis

Background

A number of studies have investigated the relationship between fibroblast growth factor receptor1 (FGFR1) gene copy number and survival in non-small cell lung cancer (NSCLC) patients. However, conclusions reported by different parties seem to be inconsistent, especially regarding the differences among different histopathologic subtypes. To derive a more precise estimate of the prognostic significance of FGFR1 gene copy number, we have reviewed published studies and carried out a meta-analysis.

Methods

The meta-analysis was conducted in accordance with PRISMA guidelines. The required data for estimation of individual hazard ratios (HRs) for survival were extracted from the publications and an overall HR was calculated.

Results

We identified 6 eligible studies, all dealing with NSCLC. The global quality score ranged 32.5-80%, with a median of 53.33%. For FGFR1 amplification in three studies including differed according to histological type, the overall RR was 0.86 which 95% confidence interval (CI) was 0.75 to 0.99 and P value was 0.048. Combined HR for the six evaluable studies was 1.17 (95% CI: 0.95 to 1.43). In the subgroup of squamous cell lung cancer (SQCC), the combined HR was 1.24 (95% CI: 0.89 to 1.73). For the Asian populations’ studies, the combined HR was 1.67 (95% CI: 1.1 to 2.52).

Conclusions

FGFR1 amplification significantly was more frequent in SQCC. FGFR1 was not associated with poorer survival in patients with NSCLC. Furthermore studies will be needed in terms of survival implications.     

Lung cancer: Preoperative pulmonary evaluation of the lung resection candidate

Lung resection provides the best chance of cure for individuals with early stage non-small cell lung cancer. Naturally, lung resection will lead to a decrease in lung function. The population that develops lung cancer often has concomitant lung disease and a reduced ability to tolerate further losses in lung function. The goal of the preoperative pulmonary assessment of individuals with resectable lung cancer is to identify those individuals whose short- and long-term morbidity and mortality would be unacceptably high if surgical resection were to occur. Pulmonary function measures such as the forced expiratory volume in 1 second and the diffusing capacity for carbon monoxide are useful predictors of postoperative outcome. In situations in which lung function is not normal, the prediction of postoperative lung function from preoperative results and the assessment of exercise capacity can be performed to further clarify risks. Published guidelines help to direct the order of testing, permitting us to offer resection to as many patients as possible.     

切除修复交叉互补基因1基因多态性与肺癌易感性meta分析

目的 探讨切除修复交叉互补基因1(ERCC-1)rs3212986位点多态性与肺癌易感性的关系.方法 使用PubMed数据库检索2013年5月以前相关文献,按纳入标准搜索研究ERCC-1rs3212986C/T多态性与肺癌易感性相关的文献,采用STATA软件进行统计分析.结果 共有5 009例肿瘤患者和5 542名对照个体被纳入荟萃分析.分析表明ERCC-1 rs3212986 C/T多态性与肺癌易感性有统计学相关性(等位基因比P=0.043,OR =0.90,95％CI:0.81～0.99).结论 ERCC-1rs3212986C/T多态性与肺癌易感性存在一定的相关性,等位基因T可能会增加肺癌的易感性.     

Risk factors and survival analysis of arrhythmia following lung cancer surgery: a retrospective study

BackgroundSurgical treatment of lung cancer is one of the important treatments for early-stage non-small cell lung cancer (NSCLC). However, arrhythmia, especially atrial fibrillation (AF) and supraventricular arrhythmia, are quite common among patients after surgical treatment of lung cancer. The impact of postoperative arrhythmia (PA) on survival is rarely reported. Our aim was to evaluate the risk factors of PA and its impact on overall survival (OS) after lung cancer surgery.MethodsA total of 344 patients diagnosed with NSCLC who underwent lung cancer surgery were enrolled in this study. These patients were divided into two groups based on the occurrence of PA. Univariate and multivariate logistic regression analyses were conducted to identify the risk factors of PA. The Kaplan-Meier method was applied to show the OS differences between the two groups.ResultsThe incidence of PA was 16% (55/344). Among these 55 patients, 20 had AF, 30 had sinus tachycardia, and 5 had premature beats. A total of 332 patients underwent lung cancer radical resection. Operation type (P<0.001), preoperative abnormal ECG (P=0.032), transfusion (P=0.016), postoperative serum potassium concentration (P=0.001) and clinical stage (P<0.05) were risk factors for PA. PA (HR 2.083, 95% CI, 1.334–3.253; P=0.001), age (HR 1.543, 95% CI, 1.063–2.239; P=0.025) and mediastinal lymph node metastasis (HR 2.655, 95% CI, 1.809–3.897; P<0.001) were independent prognostic risk factors for OS by multivariate cox analysis.ConclusionsWe identified PA as an independent prognostic risk factor to predict poor OS in patients who underwent lung cancer surgery and had risk factors for PA. We therefore provides guidance for PA in improving the prognosis of lung cancer patients.     

肺癌患者白介素1受体拮抗剂基因多态性的研究

目的 对肺癌患者和健康人的白介素1受体拮抗剂基因(interleukin-1 receptor antagonist gene,IL-1RN)多态性进行研究,探讨IL-1RN与肺癌易感性的关系.方法 采用聚合酶链式反应技术对148例肺癌患者和150名健康对照者的IL-1RN基因多态性进行分析.结果 Ⅱ类等位基因(IL-...     

非小细胞肺癌患者血浆Cripto-1的水平及临床意义

目的探讨非小细胞肺癌患者(NSCLC)血浆中CR-1的表达水平与患者临床病理特征之间的关系,及其对肺癌预后的判断价值。方法收集35例正常人血浆,40例良性肺部疾病患者和102例NSCLC患者血浆,用酶联免疫吸附法(ELISA)检测血浆CR-1表达水平。结果NSCLC患者血浆CR-1水平远高于健康对照组(P<0.05),良性肺部疾病患者血浆CR-1浓度虽也有一定的升高,但较之肺癌组低,二者间差异有显著性(P<0.05)。肺癌患者血浆CR-1水平与淋巴结转移状态和临床分期有关(P<0.01)。血浆CR-1与患者生存期密切相关,生存>12个月患者血浆CR-1明显低于<12个月者(P<0.01)。结论血浆CR-1与NSCLC的病程进展及生存期相关,是一种有价值的预后判断指标。     

Expression of paired basic amino acid-cleaving enzyme 4 (PACE4) correlated with prognosis in non-small cell lung cancer (NSCLC) patients

Background

Paired basic amino acid-cleaving enzyme 4 (PACE4) was shown to enhance tumor cells proliferation and invasive. This study provides the first investigation of PACE4 expression in non-small cell lung cancer (NSCLC) and the correlation with clinicopathologic features, prognostic indicators of 172 cases.

Methods

Quantitative real-time PCR (RT-PCR) and immunofluorescence (IF) were applied to detect PACE4 expression in NSCLC and 16HBE cell lines, then 172 consecutive NSCLC and 15 normal lung tissues were studied through immunohistochemistry (IHC). The association between PACE4 expression and clinicopathological parameters was evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of PACE4 expression on survival.

Results

PACE4 expression in NSCLC were significantly higher than normal lung cell and tissues (P<0.05). PACE4 had cytoplasmic expression and was observed in 111 of the 172 (64.5%) NSCLC patients. Clinicopathologically, PACE4 expression was significantly associated with lymph node metastasis (N stage) (P=0.007), and clinical stage (P=0.024). Multivariable analysis confirmed that PACE4 expression increased the hazard of death after adjusting for other clinicopathological factors [hazards ratio (HR): 1.584; 95% confidence interval (CI): 1.167-2.151; P<0.001]. Overall survival (OS) was significantly prolonged in PACE4 negative group when compared with PACE4 positive group (5-year survival rates, 23.1% vs. 54.5%, log-rank test, χ²=17.717, P<0.001), as was disease-free survival (DFS) (5-year survival rates, 23.4% vs. 55.4%, log-rank test, χ²=20.486, P<0.001).

Conclusions

Our results suggest that positive expression of PACE4 is an independent factor for NSCLC patients and it might serve as a potential prognostic biomarker for patients with NSCLC.     

A high density of PD-L1-expressing immune cells is significantly correlated with favorable disease free survival in nonmetastatic colorectal cancer

The impact of immune cells (ICs) expressing various markers remains poorly understood in nonmetastatic colorectal cancer patients who have undergone colectomy. Here, we aimed to clarify the correlation between IC density and clinical parameters and survival.Programmed death protein-1 (PD-1), programmed cell death protein ligand-1 (PD-L1), clusters of differentiation (CD)-3, CD-8, and CD45RO immunostaining was performed for 421 patients using tissue microarray and automatic counting. Tumor stroma area immune density was assessed in comparison to clinical histological factors and surgical outcomes.High-density CD-8 expression was significantly associated with current smoking habits or a smoking history (P = .006). High-density of PD-1 expression was correlated with Lynch syndrome patients (P < .001) and with patients who did not consume alcohol (P = .034). A significant decrease in CR45RO expression density was associated with aging (P = .002 and r = –0.014), and high-density CD-3, CD-8, and PD-1 expression was significantly associated with right colon tumor location (P < .001). High CD-3 and PD-L1 expression was significantly associated with early tumor T-staging (P = .018 and P = .002). High-density PD-1 expression was significantly correlated with mucinous type adenocarcinoma (P = .027) and poor differentiation (P < .001). For treatment outcomes, multivariate analysis confirmed that patients exhibiting high-density PD-L1 expression possessed significantly longer disease free survival (adjusted hazard ratio: 0.752, 95% confidence interval [CI]: 0.61–0.92, P = .006) and overall survival (adjusted hazard ratio: 0.872, 95% CI: 0.75–1.91, P = .064)Significantly varied density in IC subsets was related to distinct demographic or clinic-histological factors. The presence of high-density PD-L1-expressing ICs is an independent favorable prognostic factor for disease free survival and overall survival among stage I to III colorectal cancer patients.