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Tetraspanin CD151 has been identified as a tumor promoter, which is upregulated in various malignant cell types. However, the function of CD151 and its underlying mechanism in renal cell carcinoma is still unknown. In this study, we detected the expression of CD151 in RCC cells and tissues and explored its regulatory mechanism. We found that CD151 was upregulated in renal cell carcinoma tissues and cells and its expression was significantly associated with tumor stage (p=0.019) and survival (p=0.001) by analyzing tissue microarrays. After silencing of CD151 via lentivirus vector in Caki-1 and Caki-2 cells, reduced ability of migration and invasion were detected with downregulation of CD151. The opposite results were observed in cells with CD151 overexpression. Furthermore, western blotting was performed to investigate the influence of CD151 on epithelial-to-mesenchymal transition, matrix metalloproteinase 9 and TGF-β1/Smad signaling pathway in RCC. Subsequently, upregulating the protein level of transforming growth factor-β1 in cells with silencing of CD151 could rescue the malignant behaviors inhibited, which indicated that CD151 may play its promoting role in RCC partially by stimulating the expression of TGF-β1. Conclusively, CD151 might exhibit a prominent role in migration and invasion of RCC cells via activating TGF-β1/Smad signaling pathway., Competing Interests: CONFLICTS OF INTEREST All authors have read and approved the final manuscript, and do not have a commercial or other association that might pose a conflict of interest.

Recent studies have shown that tripartite motif-containing protein 29 (TRIM29) had prognostic values in several cancers. However, different studies have been inconsistent. We conducted a meta-analysis to elucidate the precise predictive value of TRIM29 in various human malignant disease. Eleven eligible studies with 2046 patients were ultimately enrolled in this meta-analysis. Heterogeneity between studies was assessed using I 2 statistics. Pooled Hazard ratios (HRs) with 95% confidence intervals (CIs) for patient survival and disease recurrence were calculated to investigate the correlation between TRIM29 expression and cancer prognosis. The results identified an important link between upregulated TRIM29 expression and poor prognosis in patients with multiple human malignant neoplasms in terms of recurrence-free survival (RFS)/disease-free survival (DFS) (HR = 1.66, 95% CI 1.36-2.04) but favorable progression-free survival (PFS)/metastasis-free survival (MFS) (HR = 0.37, 95% CI 0.16-0.85). We found that high TRIM29 expression predicted no significant impact on overall survival (OS) (HR = 1.32, 95% CI 0.90-1.93). Subgroup analyses showed that high TRIM29 expression predicted poor OS in Asians (HR = 2.21, 95% CI 1.78-2.74) but favorable OS in Caucasian (HR = 0.47, 95% CI 0.25-0.89). TRIM29 might play an essential role in carcinogenesis of multiple human malignant neoplasms and could serve as a biomarker for the prediction of patients' prognosis., Competing Interests: CONFLICTS OF INTEREST The authors report no conflicts of interest in this work.

The calpain 2 (CAPN2) is upregulated in various malignant carcinomas. Previous studies have reported that CAPN2 functioned as an oncogenic factor in human cancers. However, its clinical role and potential effects on cell metastasis and proliferation in renal cell carcinoma (RCC) remain unknown. In this study, we evaluated the mRNA and protein levels of CAPN2 in human RCC specimens, matched normal specimens, and RCC cell lines using quantitative Real-time PCR (RT-PCR) and western blot. Immunohistochemistry of 74 RCC tissues in a tissue microarrays (TMAs) and normal kidney tissues were performed. Kaplan-Meier survival curve analyses were conducted to measure the correlation between CAPN2 and tumor prognosis. Cell migration, invasion and proliferation were detected by transwell assays and Cell Counting Kit-8 (CCK-8) assays. CAPN2 exhibited a significant overexpression in human RCC tissues and cell lines compared with adjacent non-tumor tissues and normal human proximal tubule epithelial cell line HK-2. Strong staining of CAPN2 was associated with higher clinical stage and histological grade. In addition, sh-CAPN2 could significantly inhibit migration, invasion and proliferation of 769-P and CAKI-1 cells. Conversely, increased cell biological behaviors were observed in CAPN2-OV CAKI-2 cells. Moreover, the subsequent mechanism investigation suggested that CAPN2 promoted tumor progression by activating AKT/mTOR signaling, enhancing epithelial mesenchymal transition (EMT) and MMP9 levels. The present study indicates that CAPN2 may act as a prominent indicator for RCC progression and a novel therapeutic target for RCC patients., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Systemic inflammation and hematological markers have prognostic value in patients with esophageal squamous cell carcinoma (ESCC). The objective of this study was to evaluate the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), combined neutrophil-platelet (CNP) score, and hemoglobin (Hb) to inform treatment decisions and predict outcomes in patients with locally advanced ESCC treated with chemoradiotherapy (CRT). A total of 168 patients with locally advanced ESCC were retrospectively evaluated. Patients were stratified by marker value using a receiver operating characteristic curve analysis to determine the cutoff point. Logistic regression was used to identify markers associated with sensitivity to treatment. Overall survival (OS) was calculated by the Kaplan-Meier method. Multivariate Cox logistic regression modeling was used to assess the influences of OS. Smoking history, tumour site, clinical stage, NLR, PLR, CNP, and Hb ( p ≤ 0.05) were associated with the sensitivity to therapy. In multivariate analysis, a high CNP score was independently associated with poor treatment sensitivity (OR = 2.066, p = 0.021). Univariate analysis revealed that PLR, CNP, and Hb levels were associated with OS, and Cox multivariate analysis found that CNP (HR = 1.47, p = 0.027) and Hb level (HR = 0.44, p = 0.007) were independent predictors of OS. In conclusion, CNP and Hb are inexpensive and universally available prognostic markers in patients with locally advanced ESCC patients. CNP score is a systemic inflammatory marker that predicted sensitivity to CRT., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest concerning this article.

Dietary restriction has been recognized as a healthy and natural therapy for cancer. It is reported that different forms of dietary restriction can promote anti-tumor immunity. However, it is not clear how fasting affects tumor-associated macrophages (TAMs). This study aims to investigate the relationship between fasting and antitumor immunity in terms of tumor-associated macrophages. In vivo, the results showed that alternate day fasting for 2 weeks inhibitted the tumor growth of mice without causing a reduction of body weight. Meanwhile, M2 polarization of tumor-associated macrophages in tumor tissues of alternate day fasting group was also decreased. In vitro , fasting induced the autophagy of CT26 cells, decreased the generation of extracellular adenosine by supressing the expression of CD73 in CT26 cells. Decreasing adenosine inhibitted M2 polarization of RAW264.7 cells through inactivating JAK1/STAT3 signal pathway in fasting condition. Eventually, the proliferation of CT26 cancer cells declined on account of fasting-facilitated antitumor immunity. These results suggested that fasting suppressed M2 polarization of tumor-associated macrophages to inhibit tumor growth through decreasing the level of adenosine in the tumor microenvironment both in vivo and in vitro . This process was associated with increasing autophagy of tumor cells., Competing Interests: CONFLICTS OF INTEREST There are no conflicts of interest to disclose.

To summarize and clarify the association between vascular endothelial growth factor ( VEGF ) and vascular endothelial growth factor receptor ( VEGFR ) polymorphisms and the outcome in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib. A total of 8 studies including 900 patients were analyzed in this systematic review after screening the database of PubMed, EMBASE and Web of Science. Hazard ratios (HRs) with 95% confidence interval (CI) were used to evaluate the strength of the association. VEGFR1 rs9582036 AA/AC carriers and rs9554320 CC/AC carriers had more favorable overall survival (OS) in patients with mRCC treated with sunitinib ( n = 3), but not in progression-free survival (PFS). In addition, VEGFA rs2010963 was associated with poorer PFS of mRCC ( n = 1). VEGFA rs699947 was significant in predicting PFS by univariate analysis, but showed no statistical significance in OS ( n = 1). VEGFR2 rs1870377 was verified to be associated with sunitinib OS ( n = 1). Furthermore, patients with VEGFR3 rs307826 and rs307821 had shorter PFS and OS during sunitinib therapy ( n = 2, respectively). Our results suggested that VEGF and VEGFR polymorphisms were associated with outcomes in sunitinib treated mRCC patients, especially VEGFR1 polymorphisms. However, considering the limited study numbers, its clinical application in sunitinib treated mRCC still needs further confirmation., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interests.

Recent studies have demonstrated that microRNA-148/152 family emerges as a attractive biomarker for predicting tumor prognosis and progression. However, outcomes of different studies are controversial. Eligible Literature were searched through online databases: PubMed, EMBASE and Web of Science. A total of 24 eligible studies were ultimately enrolled in this meta-analysis. Results indicated that overexpression of miR-148/152 family was significantly correlated with enhanced overall/cause-specific survival (OS/CSS) (HR=0.63, 95% CI: 0.54-0.74). Stratified analysis indicated that high miR-148a and miR-148b expression predicted favorable OS/CSS (HR=0.76; 95% CI: 0.69-0.90) and (HR=0.49; 95% CI: 0.39-0.61), while miR-152 developed no significant impact (HR=0.40, 95% CI: 0.12-1.29). MiR-148/152 family was distinctly associated with superior OS/CSS in Asian (HR=0.53, 95% CI: 0.44-0.64), but not in Caucasian (HR=0.96, 95% CI: 0.82-1.13). Futhermore, miR-148/152 family expression also predicted longer disease/relapse/progression-free survival (DFS/RFS/PFS) (HR=0.37, 95% CI: 0.16-0.88). A significantly favorable DFS/RFS/PFS was observed in Asian (HR=0.21, 95% CI: 0.06-0.81) than that in Caucasian (HR=0.76, 95% CI: 0.31-1.87). miR-148/152 family overexpression also predicted longer DFS/RFS/PFS in tissues (HR=0.11, 95% CI: 0.01-0.98), but not in plasma/serum (HR=0.67, 95% CI: 0.38-1.18). Our meta-analysis demonstrated that overexpression of miR-148/152 predicted enhanced OS/CSS and DFS/RFS/PFS of cancer patients. MiR-148a/b family may serve as a potential prognostic factor in multiple human malignancies.

NOD-like receptor (NLR) NLRP3 inflammasome activation has been implicated in the progression of non-alcoholic fatty liver disease (NAFLD) from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH). It has been also shown that palmitic acid (PA) activates NLRP3 inflammasome and promotes interleukin-1β (IL-1β) secretion in Kupffer cells (KCs). However, the specific mechanism of the NLRP3 inflammasome activation is unclear. We studies the molecular mechanisms by investigating the roles of Thioredoxin-interacting protein (TXNIP) and NLRP3 on NAFLD development in patients, high-fat diet (HFD)-induced NAFL and methionine choline deficient (MCD) diet-induced NASH in wild type (WT), TXNIP-/- (thioredoxin-interacting protein) and NLRP3-/- mice, and isolated KCs. We found that the expressions of NLRP3 and TXNIP in human liver tissues were higher in NASH group than in NAFL group. Furthermore, co-immunoprecipitation analyses show that activation of the TXNIP-NLRP3 inflammasome protein complex occurred in KCs of NASH WT mice rather than NAFL WT mice, thus suggesting that the formation and activation of this protein complex is mainly involved in the development of NASH. NLRP3-/- mice exhibited less severe NASH than WT mice in MCD diet model, whereas TXNIP deficiency enhanced NLRP3 inflammasome activation and exacerbated liver injury. PA triggered the activation and co-localization of the NLRP3 inflammasome protein complex in KCs isolated from WT and TXNIP-/- but not NLRP3-/- mice, and most of the complex co-localized with mitochondria of KCs following PA stimulation. Taken together, our novel findings indicate that TXNIP plays a protective and anti-inflammatory role in the development of NAFLD through binding and suppressing NLRP3.

The tetraspanin KAI1/CD82 was identified as a tumor metastasis suppressor that downregulated in various malignant cell types. However, the function of CD82 and its underlying anti-metastasis role in renal cell carcinoma (RCC) is still unraveled. Here, we investigated the expression of CD82 in RCC and explored its regulatory mechanism in RCC cell lines. We found that CD82 was down-regulated in RCC tissues and cells and its expression was significantly associated with histological grade(p=0.041), tumour stage (p=0.036) and tumor size(p=0.020) by analyzing tissue microarrays. After upregulation of CD82 through lentivirus, reduced ability of migration and invasion in Caki-1 cells were detected. In contrast, gene silencing of CD82 by small interfering RNA promoted metastatic and invasive potential of 786-O cells. Furthermore, Western blot was performed to identify the influence of CD82 on MMP family and TGF-β1/Smad pathway in RCC. Subsequently, upregulating protein level of TGF-β1 with the overexpression of CD82 could rescue the malignant behaviors inhibited by CD82 which indicated that CD82 played its inhibitory role in RCC partially by attenuating the expression of TGF-β1. Taken together, CD82 played a prominent role in migration and invasion of RCC cells and it might exhibit its inhibitory role in RCC metastasis via block TGF-β1/Smad signaling pathway., Competing Interests: CONFLICTS OF INTEREST We declare that we have no conflicts of interest.

Recent studies have shown that matrix metalloproteinases (MMPs) might be a biomarker for predicting outcomes of bladder cancer. However, the prognostic value of overexpression of MMPs in bladder cancer is debatable and the studies are inconsistent. Therefore, this meta-analysis was performed to clarify the specific association and prognostic value of overexpression of MMPs in bladder carcinoma. Relevant studies were identified by searching PubMed, EMBASE, and the Web of Science. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for disease-specific survival (DSS), overall survival (OS), disease/recurrence-free survival (DFS/RFS), and progression/metastasis-free survival (PFS/MFS) were analyzed to determine the prognostic value of MMPs. In total, eighteen applicable studies were included in this meta-analysis. We found that high expression of MMPs significantly correlated with a poor DSS and OS (HR=1.66; 95% CI = 1.38-2.01 and HR= 1.67; 95%CI= 1.26-2.22). MMPs also predicted tumor progression and metastasis with a pooled HR of 3.03 (95% CI 1.98-4.64). However, high MMPs expression had no pivotal impact on DFS/RFS (HR= 1.21; 95% CI= 0.96-1.53). With the purpose of better understanding the prognostic role of MMPs in patients wirh bladder carcinoma, we carried out this systematic review and meta-analysis.

Malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) is a predicted oncoprotein that demonstrates tumorigenic activity in vivo; however, the mechanisms involved are unknown. Macrophages are divided into the pro-inflammatory M1 and anti-inflammatory/protumoral M2 subtypes. Tumor cells can induce M2 polarization of tumor-associated macrophages (TAMs) to promote metastasis; but the underlying pathways require to be elucidated. In this study, we detected a positive association between MFHAS1 expression in TAMs and human colorectal cancer (CRC) TNM stage. Supernatant of CT26 murine CRC cells induced MFHAS1 expression in RAW264.7 murine macrophages. Additionally, CT26 supernatant induced the M2 marker CD206 and activated the pro-M2 STAT6 and KLF4 signaling in control but not MFHAS1-silenced RAW264.7 macrophages. Moreover, supernatant of control, but not MFHAS1-silenced macrophages promoted CT26 cell proliferation, migration and epithelial-mesenchymal transition. Compared with control macrophages, MFHAS1-silenced macrophages showed significantly reduced protumoral effects in vivo. Together, these results suggested that CRC cells induce M2 polarization of TAMs through MFHAS1 induction and subsequent STAT6 and KLF4 activation to promote CRC progress. Finally, similar to CT26 supernatant stimulation, peroxisome proliferator-activated receptor-γ (PPARγ) activation by rosiglitazone induced M2 polarization of RAW264.7 macrophages through MFHAS1-dependent pathway. Our results highlight the role of MFHAS1 as a regulator of macrophages polarization and CRC progress.

Germline HOXB13 G84E mutation (rs138213197) has been described associated with prostate cancer (PCa) susceptibility but results of different studies are inconsistent. We conducted this meta-analysis to evaluate the specific role of this mutation. Relevant available studies were identified by searching the databases Pubmed, Embase and Web of Science. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure the strength of the association. Subgroup analysis were performed to evaluate the specific role of rs138213197 in disease aggressiveness, diagnostic age and family history. Furthermore, trial sequential analysis (TSA) was conducted for the first time to estimate whether the evidence of the results is sufficient. Our results indicated that significant increased PCa susceptibility was associated with rs138213197 compared with non-carriers (OR = 3.38, 95% CI: 2.45-4.66). Besides, in subgroup analysis, HOXB13 G84E variant was obviously associated with early onset (OR = 2.90, 95% CI: 2.24-3.75), affected relatives (OR = 2.60, 95% CI 2.19-3.10) and highly aggressive disease (OR = 2.38, 95% CI 1.84-3.08). By TSA, the findings in the current study were based on sufficient evidence. Therefore, our results indicated that the G84E mutation in HOXB13 gene might increase susceptibility to PCa.

Several animal and observational studies have evaluated the effects of neuraxial anesthesia on the recurrence and survival of cancer surgery; studies reported benefit, whereas others did not. To provide further evidence that neuraxial anesthesia(combined with or without general anesthesia (GA))may be associated with reduced cancer recurrence and long-term survival after cancer surgery, we conducted this meta-analysis. A total of 21 studies were identified and analyzed, based on searches conducted using PubMed, Web of Science, EMBASE database and the Cochrane Database of Systematic Reviews. After data abstraction, adjusted hazard ratios (HR) with 95% confidence intervals (CIs) were used to assess the impact of neuraxial anesthesia (combined with or without GA) and GA on oncological outcomes after cancer surgery. For overall survival (OS), a potential association between neuraxial anesthesia and improved OS (HR 0.853, CI 0.741-0.981, P = 0.026, the random-effects model) was observed compared with GA. Specifically, we found a positive association between neuraxial anesthesia and improved OS in colorectal cancer (HR 0.653, CI 0.430-0.991, P = 0.045, the random-effects model). For recurrence-free survival (RFS), a significant association between neuraxial anesthesia and improved RFS (HR 0.846, CI 0.718-0.998, P = 0.047, the random-effects model) was detected compared with GA. Our meta-analysis suggests that neuraxial anesthesia may be associated with improved OS in patients with cancer surgery, especially for those patients with colorectal cancer. It also supports a potential association between neuraxial anesthesia and a reduced risk of cancer recurrence. More prospective studies are needed to elucidate whether the association between neuraxial use and survival is causative.