Expression and prognostic value of FOXP1 in esophageal squamous cell carcinoma

BackgroundForkhead box protein P1 (FOXP1) has been suggested as a prognostic marker in several malignant tumors. However, the significance of FOXP1 in esophageal squamous cell carcinoma (ESCC) is still unclear. The purpose of this study was to investigate the expression pattern of FOXP1 in normal esophageal tissue and ESCC and to analyze the clinicopathological significance and prognostic value of FOXP1 in ESCC.MethodsFOXP1 was detected by immunohistochemistry using tissue microarrays containing tumor tissues and adjacent normal tissues from 270 ESCC patients with oncological follow-up data.ResultsNormal esophageal tissues predominantly showed an exclusive nuclear FOXP1 (n-FOXP1) expression pattern, and no exclusive cytoplasmic FOXP1 (c-FOXP1) staining was found. In ESCC, the expression rates of exclusive n-FOXP1-positive, exclusive c-FOXP1-positive, both nuclear and cytoplasmic positive and complete negative were 14.4%, 28.9%, 10.4% and 46.3%, respectively. High n-FOXP1 expression was significantly correlated with decreased postoperative recurrence and distant metastasis (P < 0.05). Furthermore, elevated c-FOXP1 expression was significantly associated with regional lymph node metastasis and distant metastasis (P < 0.05). High c-FOXP1 expression had an effect on shorter overall survival (OS) time, but the difference was not statistically significant (P > 0.05). Kaplan–Meier analysis showed that ESCC patients with high n-FOXP1 expression survived significantly longer than patients with low n-FOXP1 expression. Multivariate analysis confirmed that patients with high n-FOXP1 staining exhibit good prognosis and n-FOXP1 was an independent factor for ESCC prognosis.ConclusionsOur results suggest that FOXP1 plays an essential role in ESCC progression and prognosis and may be a useful biomarker for predicting survival.     

Prognostic and clinicopathological significance of CapG in various cancers: Evidence from a meta-analysis

BackgroundThe gelsolin-like actin-capping protein (CapG) is an actin-binding protein in the gelsolin superfamily. Increasing evidence indicates that CapG is highly expressed in various types of cancer. However, the role of CapG in malignant tumors is still controversial. Therefore, we conducted a meta-analysis to assess the prognostic value and clinicopathological significance of CapG in malignant tumors.MethodWe searched for eligible studies in the PubMed, Web of Science, Embase, and Cochrane databases. Stata SE12.0 software was used for quantitative meta-analysis. The hazard ratios (HRs) and odds ratios (ORs) with 95% CI were pooled to assess the relationship between CapG expression and overall survival (OS), as well as clinicopathological parameters.ResultsSixteen studies with a total of 1987 cancer patients were included in this meta-analysis. The results showed that higher CapG expression was statistically correlated with shorter OS (HR 1.70, 95% CI 1.43–1.97, P < 0.001), positive lymph node metastasis (OR 1.91, 95% CI 1.19–3.09, P = 0.008), advanced TNM stage (OR 1.87, 95% CI 1.17–3.00, P = 0.009), advanced T-primary stage (OR 2.54, 95% CI 1.08–6.00, P = 0.033) and male sex (OR 1.77, 95% CI 1.23–2.56, P = 0.002). However, no significant correlation was observed between increased CapG expression and advanced age, larger tumor size, differentiation, or advanced histopathologic grading (P > 0.05).ConclusionsHigh CapG expression is associated with a poor prognosis and worse clinicopathological parameters in various cancers. CapG is a potential prognostic biomarker and a possible clinicopathological predictive factor for various cancers.     

Increased HIF-1alpha expression in tumor cells and lymphocytes of tumor microenvironments predicts unfavorable survival in esophageal squamous cell carcinoma patients

The expression of hypoxia-induced factor (HIF)-1α is up-regulated in tumor microenvironments under hypoxia condition. However, the prognostic significance of HIF-1α in esophageal squamous cell carcinoma (ESCC) is still elusive. We measured the HIF-1α expression by immunochemistry in tumor specimens from 136 resected ESCC; in the current study, the HIF-1α expression in tumor cells was significantly associated with tumor stage (P = 0.003) and lymph node metastasis (P = 0.006); whereas the HIF-1α expression in tumor-infiltrating lymphocytes (TILs) had no relationship with patients’ clinicopathological parameters. Patients with high HIF-1α expression in tumor cells or in TILs showed worse survival related to those with low HIF-1α expression. Multivariate analysis demonstrated that expression of HIF-1α in TILs was an independent factor for DFS (P = 0.007) and OS (P = 0.013). Additionally, the expression of HIF-1α in tumor cells was an independent factor for DFS (P = 0.037) and OS (P = 0.033) in locoregional ESCC patients, whereas the expression of HIF-1α in TILs was an independent factor for DFS (P = 0.048) and OS (P = 0.039) in metastatic ESCC patients. Correlation analysis revealed that expressions of HIF-1α in tumor cells and in TILs were positively correlated, and patients with combined high HIF-1α in both tumor cells and TILs had the worst survivals (P < 0.05). These findings suggest that the HIF-1α expressions in different cell populations of ESCC microenvironments have different clinical relevance and prognostic impact on patients.     

Impact of chemokine receptor CXCR3 on tumor-infiltrating lymphocyte recruitment associated with favorable prognosis in advanced gastric cancer

Chemokine receptor CXCR3 has been proved to play an important role in tumorigenesis and tumor progression in many malignancies, but its precise efficacy on gastric cancer (GC) has not been evaluated yet. The present study was aimed to explore the correlation of chemokine receptor CXCR3 with tumor-infiltrating lymphocytes (TILs) and prognosis in advanced gastric cancer (GC). Expression of CXCR3 and CD4+, CD8+ TILs was conducted in 192 advanced GC specimens and 48 corresponding paracancerous tissues by immunohistochemical (IHC) analysis. CXCR3 expression in GC tissues was significantly higher than that in paracancerous tissues (P<0.001) and CD8+, CD4+ TILs infiltration increased with high CXCR3 expression (P=0.032 and P<0.001, respectively). Our study showed significantly lower CXCR3 expression in patients with greater tumor invasion depth and lymph node metastasis compared with patients with lesser tumor invasion depth and without lymph node metastasis (P=0.002 and P=0.001, respectively). Univariate analysis indicated that patients with high CXCR3 expression and high CD8+ TILs infiltration had longer overall survival (OS) (log-rank test, P<0.001 and P=0.002, respectively). Univariate and multivariate analyses indicated that CXCR3 expression was an independent prognostic factor for OS (P=0.002). The present study suggested that CXCR3 expression was upregulated in advanced GC and was associated with increased CD4+, CD8+ TILs infiltration and improved OS. Therefore, CXCR3 overexpression is implicated as a favorable prognostic biomarker in human advanced GC.     

Overexpression of Arginase-1 is an indicator of poor prognosis in patients with colorectal cancer

AimArginase-1 (Arg-1) metabolizes l-arginine to l-ornithine and urea. It has been documented to have a role in various malignancies. However, the relationship between Arg-1 expression and clinicopathological characteristics of colorectal cancer (CRC) patients remains to be elucidated. The present study aimed to analyze the expression and prognostic value of Arg-1 in patients with CRC.Material and methodsThe mRNA and protein expressions of Arg-1 in fresh colorectal cancer tissue specimens and the corresponding noncancerous tissue specimens were examined by RT-qPCR (n = 24) and western blot analysis (n = 17). Arg-1 expression levels were determined in paraffin-embedded CRC tissue specimens (n = 236) by immunohistochemistry. The associations of Arg-1 expression and clinicopathological features and clinical prognosis in 236 CRC patients were analyzed.ResultsThe expression levels of Arg-1 were significantly higher in the CRC tissues compared with the matched noncancerous tissues, and elevated Arg-1 expression was remarkably associated with stage III-IV tumors (P = 0.007), lymph node metastasis (P = 0.019) and a plasma albumin concentration <35 g/l (P = 0.022). Kaplan-Meier analysis indicated that Arg-1 overexpression was associated with adverse prognoses for overall survival (OS) (P < 0.001) and disease-free survival (DFS) (P < 0.001) in all cases. Further analysis revealed that the patients with high Arg-1 expression had significantly shorter OS and DFS at the advanced stages (III + IV) (P = 0.032 for OS, and P = 0.012 for DFS) but not at the early stages (I + II) (P = 0.194 for OS, and P = 0.065 for DFS). Multivariate analysis revealed that Arg-1 overexpression was an independent prognostic factor for OS (P = 0.002) and DFS (P < 0.001) in patients with CRC.ConclusionThe data indicated that Arg-1 overexpression in CRC may be a marker that can discriminate subgroups of patients with a poor prognosis.     

Association between carbonic anhydrase 9 expression and poor prognosis in sinonasal squamous cell carcinoma

ObjectivesCarbonic anhydrase 9 (CA9), as a member of the carbonic anhydrase enzyme family, was an endogenous marker of hypoxia. Previous studies suggested CA9 expression was correlated with poor prognosis in multiple types of malignancies. Therefore, this study was to evaluate the role of CA9 in sinonasal squamous cell carcinoma (SNSCC) and to determine whether this biomarker was associated with patient clinicopathologic characteristics and prognosis.MethodsWe assessed 63 patients diagnosed with SNSCC in 2013–2017 who underwent curative surgery. Tumor specimens was immunohistochemically analyzed for CA9 expression. The expression levels of CA9 was evaluated in relation to clinicopathological factors and prognosis.ResultsPositive expression of CA9 was observed in 21 (33.3%) patients and was significantly correlated with local recurrence (p = 0.016), overall survival (OS) (p = 0.003) and disease-free survival (DFS) (p = 0.002). In Cox's multivariate analysis, CA9 expression was an independent negative prognostic factor for OS (p = 0.048) and DFS (p = 0.019).ConclusionsOur findings demonstrated that CA9 overexpression could be used as an independent prognostic biomarker and therapeutic target in SNSCC.     

Identification of long noncoding RNA TC0101441 as a novel biomarker for diagnosis and prognosis of gastric cancer

The present work aimed to explore the prognostic values of lncRNA TC0101441 (TC0101441) in patients with gastric cancer (GC). The expression of TC0101441 in a total of 159 GC specimens and matched normal specimens was detected by quantitative RT-PCR. ROC assays were conducted to determine the diagnostic value of TC0101441 expression in GC patients. The association of TC0101441 expression with clinical characteristics of 159 patients was analyzed using chi-square test. Kaplan-Meier methods were employed to determine the prognostic value of TC0101441 expression in the survival rate of GC patients. Multivariate Cox regression assays were used to identify whether TC0101441 could be a prognostic biomarker for GC patients. We found that TC0101441 expression was significantly increased in GC specimens compared to that in the normal specimens (P < 0.01). High TC0101441 expression was correlated with lymphatic metastasis (P = 0.027) and TNM stage (P = 0.015). TC0101441 could distinguish GC specimens from adjacent normal gastric specimens with an area under the receiver operating characteristic curve (AUC) of 0.8082. Survival data revealed that patients with high TC0101441 expression had worse overall survival (P = 0.0009) and disease-free survival (P < 0.0001) rates than those with low TC0101441 expression. Multivariate assays showed that TC0101441 expression was an independent biomarker for GC patients. The present study suggested that TC0101441 expression was increased in GC and may be aprognostic and diagnostic biomarker for GC.     

Heat shock protein 70 (HSP70) expression is associated with poor prognosis in intestinal type gastric cancer

Heat shock protein 70 (HSP70) is a molecular chaperone which plays an important role in cellular protection against various stressful stimuli and in the regulation of cellular growth and apoptosis. This study was conducted in gastric carcinoma (GC) to assess correlations of HSP70 expression with clinicopathological parameters and overall survival (OS). Tissue microarray blocks were constructed from 172 GCs and immunohistochemically stained for HSP70. Low HSP70 expression was found in 122 GCs (71 %), whereas 50 (29 %) had high expression. HSP70 expression was higher in tumours in the cardia (p?=?0.008), with non-signet ring cell histology (p?<?0.001), of intestinal type (p?=?0.045) and of higher pathological T stage (p?=?0.026). When considering the cohort as a whole, HSP70 expression did not correlate with OS (p?=?0.092). In intestinal type carcinomas, however, high HSP70 expression significantly correlated with worse OS (p?=?0.034). These results suggest that HSP70 expression might be an unfavourable prognostic factor in patients with GC, especially of intestinal type.     

Increased MT2-MMP expression in gastric cancer patients is associated with poor prognosis

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that contribute to tumorigenesis and metastasis due to their ability to degrade the extracellular matrix (ECM) and basement membrane. In despite of many reports in other solid tumors, the role of membrane type-2 MMP (MT2-MMP) in gastric cancer (GC) remains to be elucidated. The aim of this study was to investigate MT2-MMP expression in human GC tissue microarray (TMA) samples using immunohistochemistry (IHC). We found that MT2-MMP expression in tumor tissues was significantly higher compared to peritumoral tissues (P < 0.01). However, there were no statistically significant differences between MT2-MMP expression and clinicopathological parameters. In addition, univariate and multivariate Cox regression analysis showed GC patients with high MT2-MMP expression have poor overall survival (OS) compared to patients with low MT2-MMP expression (P = 0.013, P = 0.040, respectively). In conclusion, MT2-MMP is involved in GC invasion and metastasis and may serve as an independent prognostic factor for GC patients.     

Aberrant expression of microRNA-26b and its prognostic potential in human cervical cancer

Background: microRNA-26b (miR-26b) is reported to be downregulated in many human malignancies and function as a tumor suppressor. However, the roles of miR-26b expression in cervical cancer progression are unclear. The aim of this study was to investigate the clinicopathological or prognostic significance of miR-26b in human cervical cancer. Methods: A cohort of 88 paired of cervical cancer and the adjacent normal cervical epithelial tissues were collected. Quantitative RT-PCR (qRT-PCR) assay was used to detect the expression of miR-26b and its correlations with clinicopathological factors were statistically analyzed. Finally, the survival was assessed by the Kaplan-Meier method and proportional hazards model. Results: The expression level of miR-26b in cervical cancer tissues was significantly lower than that in the adjacent normal cervical tissues (P<0.001). Reduced miR-26b was observed to be significantly correlated with advanced FIGO stage, higher incidence of lymph node metastasis and recurrence of cervical cancer patients (P=0.002, 0.036 and 0.029, respectively). In addition, patients with low-miR-26b expression showed poorer recurrence-free survival (RFS) and overall survival (OS) than those with high-miR-26b expression (P=0.0043 and 0.0015, respectively). Furthermore, multivariate analyses demonstrated that low miR-26b expression was an independent prognostic factor for predicting the 5-year RFS and OS of cervical cancer patients (P=0.013 and 0.007, respectively). Conclusion: Our results showed that reduced miR-26b was correlated with tumor development and poor prognosis in human cervical cancer. The status of miR-26b expression may be a potential prognostic biomarker for cervical cancer patients.     

cPLA2a correlates with metastasis and poor prognosis of osteosarcoma by facilitating epithelial-mesenchymal transition

BackgroundOsteosarcoma (OS) patients with metastasis have very dismal prognoses, and lack effective target therapies. Overexpression of cytosolic phospholipase A2 (cPLA₂) has been shown to promote progression in several types of cancers, but its functions in OS have not been investigated.Materials and methodsIn our study, the expression of cPLA₂a was detected with immunohistochemistry in 102 cases of OS. The clinical significance of cPLA₂a was evaluated by analyzing its correlation with clinicopathological factors. The prognostic significance of cPLA₂a was estimated by univariate and multivariate analysis. The oncogenic functions of cPLA₂a on cell proliferation and invasion were investigated by MTT assay and tranwell assay respectively. Western blotting was applied to detect the markers of epithelial-mesenchymal transition (EMT) after silencing cPLA₂a expression or inhibiting its activity by a specific antagonist.ResultsIn our study, high expression of cPLA₂a was significantly associated with metastasis and advanced Enneking stage. High cPLA₂a expression was significantly associated with poor prognosis and it was an independent prognostic biomarker of OS. By silencing cPLA₂a or inhibiting its activity by a specific antagonist, we demonstrated that cPLA₂a promoted cell invasion of OS cells via inducing the EMT process.ConclusionsHigh cPLA₂a expression was an independent prognostic biomarker of OS, and cPLA₂a could promote OS cell invasion via inducing the EMT process, indicating that cPLA₂a was an independent prognostic biomarker and may be an effective drug target for OS.     

15-PGDH expression as a predictive factor response to neoadjuvant chemotherapy in advanced gastric cancer

Given the various clinical and pathologic responses to neoadjuvant chemotherapy (NACT) in gastric cancer (GC), potential biomarkers that reflecting the efficacy of NACT on GC should be investigated. The aim of this study was to investigate the 15-PGDH expression response to NACT in GC patients and its relationship with prognosis of GC. Immunohistochemical method was used to assess the level of 15-PGDH expression in 56 GC patients who received NACT before surgery and 46 patients who underwent surgical treatment without NACT as well as their corresponding adjacent non-neoplastic tissues. We found that there was no correlation of 15-PGDH expression between non-cancerous gastric tissues and GC tissues (P=0.519), while 15-PGDH expression level in NACT group was higher than that in nNACT group (P=0.015). In patients with NACT, the higher level of 15-PGDH expression was significantly associated with well-moderately differentiated grade (P=0.023), I/II stage (P=0.014) and with no lymph node metastasis (P=0.016). Moreover, statistically significant differences in overall survival (OS) were found among 15-PGDH expression (log-rank test, P<0.001) and TNM stage (log-rank test, P=0.032). Most importantly, expression of 15-PGDH was found to be an independent predictive factor by multivariate analysis (Hazard ratio (HR) 0.315 [0.120-0.827], P=0.019). These findings indicated that NACT could increase 15-PGDH expression in advanced GC patients, and 15-PGDH may serve as a candidate prognostic biomarker of advanced GC response to NACT.     

Decreased expression of lncRNA loc285194 as an independent prognostic marker in cancer: A systematic review and meta-analysis

BackgroundSeveral studies have indicated that lncRNA loc285194 is aberrantly expressed in many types of cancer. This meta-analysis was performed to elucidate the potential role of lncRNA loc285194 as a prognostic marker in malignant tumors.MethodsAn electronic search of PubMed, Medline, Embase, and Web of Science was performed to identify all eligible papers related to the prognostic impact of lncRNA loc285194 expression in cancer. Hazard ratios (HR) and 95% confidence intervals (CI) were extracted from the included studies to explore the association between lncRNA loc285194 expression and patient overall and disease-free survival (OS & DFS). The odds ratios (ORs) were also calculated to assess the association between lncRNA loc285194 expression and clinicopathological parameters.ResultsA total of 14 eligible articles with 1215 patients were included in this meta-analysis. Meta-results revealed that low expression of lncRNA loc285194 was significantly correlated with poorer overall survival (OS; HR = 2.34; 95% CI, 1.78–3.06; P < 0.001) and disease-free survival (DFS; HR = 2.66; 95% CI, 1.95–3.64; P = 0.001) rates in cancer patients. Low lncRNA loc285194 expression was also found to be significantly associated with lymph node metastasis (LNM; OR = 2.17; 95% CI, 1.23–3.83; P = 0.007), and distant metastasis (DM; OR = 2.49; 95% CI, 1.26–4.91; P = 0.009).ConclusionsThis study demonstrated that decreased level of lncRNA loc285194 was associated with poor clinical outcomes for patients with different types of cancer, supporting a promising potential biomarker for prognosis and metastasis in human cancers.     

Prognostic value of long non-coding RNA FOXD2-AS1 expression in patients with solid tumors

BackgroundAlthough increasing evidence has revealed that FOXD2-AS1 overexpression exists in various solid tumors, the value of FOXD2-AS1 as a prognostic marker in such cancers remains uncertain. Accordingly, the present research aimed to assess the association of FOXD2-AS1 with cancer prognosis and predict the biological function of FOXD2-AS1.MethodsWe systematically retrieved PubMed, PMC, Web of Science, EMBASE and Wiley Online Library databases for eligible articles published up to December 2018. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to evaluate the correlation of FOXD2-AS1 expression with overall survival (OS), disease free survival (DFS) and clinicopathological characteristics. We also used five Gene Expression Omnibus (GEO) datasets from breast cancer patients to explore the relationship between FOXD2-AS1 expression and prognosis. Finally, we validated FOXD2-AS1 expression in various carcinomas and predicted its biological function based on the public databases.ResultsA total of 13 studies with 2502 tumor patients were included. The pooled HRs demonstrated that FOXD2-AS1 overexpression was significantly associated with unfavorable OS (HR = 1.39, 95%CI: 1.23–1.57, p < 0.001) and DFS (HR = 2.24, 95%CI: 1.55–3.23, p < 0.001) in tumor patients. The pooled ORs indicated that FOXD2-AS1 upregulation was related to large tumor size (OR = 1.53, 95%CI: 1.26–1.85, p < 0.001), deep invasion depth (OR = 1.99, 95%CI: 1.53–2.58, p < 0.001), distant metastasis (OR = 2.03, 95%CI: 1.69–2.43, p < 0.001) and advanced TNM stage (OR = 1.35, 95%CI: 1.06–1.72, p = 0.0150), but not to lymph node metastasis nor differentiation. Moreover, a similar pooled result for the OS of breast cancer patients was obtained (HR = 1.55, 95%CI: 1.14–2.11, p = 0.0052) by analyzing GEO data. Finally, elevated FOXD2-AS1 expression in various solid tumor tissues was verified based on The Cancer Genome Atlas (TCGA) data. Further functional prediction demonstrated that FOXD2-AS1 may participate in some cancer-related pathways.ConclusionElevated FOXD2-AS1 expression was associated with poor survival in patients with solid tumors and may serve as a potential prognostic biomarker for a variety of cancers.     

Relationship between Tertiary Lymphoid Structure and the Prognosis and Clinicopathologic Characteristics in Solid Tumors

Background: An increasing number of studies had shown that tertiary lymphoid structure (TLS) plays an important role in tumor progression. However, the prognostic role of TLS in various tumors remains controversial. This meta-analysis aims to investigate the clinicopathological and prognostic values of TLS in solid tumors.Methods: A systematic search was conducted in PubMed, EMBASE and Cochrane Library undated to November 2, 2020. Odds ratios of clinical parameters, hazard ratio (HR) of overall survival (OS), relapse-free survival (RFS), disease-free survival (DFS) and relapse rate were calculated in order to evaluate the relationship between TLS expression and clinicopathological or prognostic values in different tumors.Result: 27 eligible studies including 6647 patients with different types of tumors were analyzed. High TLS expression was associated with a longer OS (HR = 0.66, 95% CI: 0.50 - 0.86, P = 0.002) and RFS (HR = 0.61, 95% CI: 0.47 - 0.79, P = 0.0001). Moreover, high TLS levels in tumor were associated with a low risk of recurrence (HR = 0.43, 95% CI: 0.32 - 0.57, P < 0.0001). However, there was no relationship between TLS expression and DFS. Meanwhile, high TLS expression was associated with smaller tumor size (P < 0.00001) and higher tumor infiltrating lymphocytes (TILs). Furthermore, the subgroup analysis showed high TLS expression that may be associated with a lower clinical grading and N stage in breast cancer and colorectal cancer.Conclusion: High TLS expression is associated with the longer OS and RFS in solid tumors, and a lower risk of cancer relapse. Meanwhile, high TLS expression is also associated with a smaller tumor size, higher infiltration of TILs, lower clinical grading and N stage in the tumor. Therefore, high TLS expression in the tumor is a favorable prognostic biomarker for solid tumor patients.     

Clinicopathological and prognostic significance of C/EBP homologous protein (CHOP) in advanced gastric cancer

Background

Few studies have reported the clinical and prognostic significance of C/EBP homologous protein (CHOP) in advanced gastric cancer (GC). Therefore, the present study investigated the expression of CHOP in advanced GC patients to determine its potential prognostic role.

PinX1 is up-regulated and associated with poor patients’ survival in gliomas

PinX1, a conserved nuclear protein, could maintain telomere integrity and plays an important role in regulating telomerase activity. It has been reported that the expression of PinX1 is down-regulated in some cancer and associated with cancer prognosis. However, the value of PinX1 in gliomas has not been studied. In this study, two independent retrospective gliomas cohorts with the corresponding gliomas tissue microarrays (TMAs) were established to detect the expression level of PinX1 and the correlation of PinX1 expression with the clinicopathological features and the patients’ survival. Compared with non-cancerous brain tissues, PinX1 protein levels were remarkably up-regulated in gliomas (P = 0.001), and further increased from benign gliomas tissues to malignant gliomas tissues (P = 0.090). Moreover, high PinX1 expression was significantly positively associated with gliomas WHO grade in the training set (P = 0.019) and the validation set (P = 0.037). High PinX1 expression significantly correlated with a worse 5-year overall (P = 0.016) and disease-specific survival (P = 0.026). Simultaneously, the multivariate COX regression analysis showed that PinX1 was an independent unfavorable prognostic factor for 5-year overall survival (hazard ratio (HR) = 2.078, P = 0.015) and disease-specific survival (HR = 2.429, P = 0.012) after adjusting with age, sex and WHO grade in gliomas. In conclusion, PinX1 expression may serve as a prognostic and predictive biomarker for gliomas.     

XB130 expression in human osteosarcoma: a clinical and experimental study

Identifying prognostic factors for osteosarcoma (OS) aids in the selection of patients who require more aggressive management. XB130 is a newly characterized adaptor protein that was reported to be a prognostic factor of certain tumor types. However, the association between XB130 expression and the prognosis of OS remains unknown. In the present study, we investigated the association between XB130 expression and clinicopathologic features and prognosis in patients suffering OS, and further investigated its potential role on OS cells in vitro and vivo. A retrospective immunohistochemical study of XB130 was performed on archival formalin-fixed paraffin-embedded specimens from 60 pairs of osteosarcoma and noncancerous bone tissues, and compared the expression of XB130 with clinicopathological parameters. We then investigate the effect of XB130 sliencing on invasion in vitro and lung metastasis in vivo of the human OS cell line. Immunohistochemical assays revealed that XB130 expression in OS tissues was significantly higher than that in corresponding noncancerous bone tissues (P = 0.001). In addition, high XB130 expression more frequently occurred in OS tissues with advanced clinical stage (P = 0.002) and positive distant metastasis (P = 0.001). Moreover, OS patients with high XB130 expression had significantly shorter overall survival and disease-free survival (both P < 0.001) when compared with patients with the low expression of XB130. The univariate analysis and multivariate analysis shown that high XB130 expression and distant metastasis were the independent poor prognostic factor.We showed that XB130 depletion by RNA interference inhibited invasion of XB130-rich U2OS cells in vitro and lung metastasis in vivo. This is the first study to reveal that XB130 overexpression may be related to the prediction of metastasis potency and poor prognosis for OS patients, suggesting that XB130 may serve as a prognostic marker for the optimization of clinical treatments. Furthermore, XB130 is the potential molecular target for OS therapy.     

Prognostic significance of phosphorylated 4E-binding protein 1 in non-small cell lung cancer

Phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) binding protein (4E-BP1) results in release of eIF4E, which sequentially relieves translational repression and enhances oncogenic protein synthesis. We assessed the expression of phosphorylated 4E-BP1 (p-4E-BP1) in non-small cell lung cancer (NSCLC) and its correlation with clinicopathological parameters and patient survival. In addition, we investigated whether phosphorylation site made a difference in outcome. Tissue microarray blocks were generated from 73 NSCLC samples and immunohistochemically stained for p-4E-BP1 Thr37/46 and p-4E-BP1 Thr70. Both p-4E-BP1 Thr37/46 and p-4E-BP1 Thr70 were more highly expressed in squamous cell carcinoma than in adenocarcinoma (P = 0.006 and P = 0.003, respectively). Expression of p-4E-BP1 Thr70 was higher in tumours with a diameter larger than 3 cm (P = 0.024) and nodal metastasis (P = 0.053). High p-4E-BP1 Thr70 expression significantly correlated with worse overall survival (P = 0.001) and was an independent prognostic factor (hazard ratio 2.64, P = 0.004). p-4E-BP1 Thr37/46 had no prognostic significance. Phosphorylation site affected the prognostic significance of p-4E-BP1. p-4E-BP1 Thr70 is a candidate biomarker to predict poor prognosis in patients with NSCLC.