Chenkui Miao

The significance of microRNA-148/152 family as a prognostic factor in multiple human malignancies: a meta-analysis

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.

The metastasis suppressor CD82/KAI1 regulates cell migration and invasion via inhibiting TGF-β 1/Smad signaling in renal cell carcinoma

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.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.

Prognostic role of matrix metalloproteinases in bladder carcinoma: a systematic review and meta-analysis

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.

Silencing Trim59 inhibits invasion/migration and epithelial-to-mesenchymal transition via TGF-β/Smad2/3 signaling pathway in bladder cancer cells

The evolutionarily conserved genes that encode the tripartite motif (TRIM) protein family are involved in various biological processes, including cellular immunity, inflammatory reaction, antiviral activity, and tumor progression. One member of this protein family, Trim59, has been reported as a novel biomarker for the occurrence and progression of multiple human carcinomas, such as lung cancer, gastric cancer, cervical cancer, and osteosarcoma. However, little is known about the relationship between Trim59 and bladder carcinogenesis. In this study, we examined the expression of Trim59 in bladder cancer (Bca) specimens and cell lines, and investigated its biological roles in Bca cell lines. We found that Trim59 was upregulated in Bca tissues and cell lines. In addition, using transwell chamber assays and the cell scratch test, we determined that knockdown of Trim59 significantly inhibited the epithelial-mesenchymal transition (EMT) and the processes of cell invasion and migration in Bca cell lines. Furthermore, we found that downregulated Trim59 expression could also inhibit cell proliferation and promote apoptosis. As a result, we demonstrated that the effects of Trim59-induced EMT and invasion/migration in Bca cells were achieved by the activation of the transforming growth factor beta/Smad2/3 signaling pathway. Our findings also revealed that Trim59 can present oncogenic activity, and may serve as a novel candidate target for bladder carcinoma treatment.

Association between germline homeobox B13 (HOXB13) G84E allele and prostate cancer susceptibility: a meta-analysis and trial sequential analysis

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.

Effects of VEGF and VEGFR polymorphisms on the outcome of patients with metastatic renal cell carcinoma treated with sunitinib: a systematic review and meta-analysis

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.

Prognostic Role of Secretory Clusterin in Multiple Human Malignant Neoplasms: A Meta-Analysis of 26 Immunohistochemistry Studies.

Secretory clusterin (sCLU) is a potential prognostic tumour biomarker, but results of different sCLU studies are inconsistent. We conducted this meta-analysis to evaluate the precise predictive value of sCLU. Qualified studies were identified by performing online searches in PubMed, EMBASE, and Web of Science. The selected articles were divided into three groups based on scoring method for clusterin detection. Pooled hazard ratios (HRs) with 95% confidence interval (CI) for patient survival and disease recurrence were calculated to determine the correlation between sCLU expression and cancer prognosis. Heterogeneity was assessed using I2 statistics, and specific heterogeneity in different groups was analysed. Elevated sCLU was significantly associated with recurrence-free survival in groups 1 and 3 (group 1: pooled HR = 1.35, 95% CI = 1.01 to 1.79; group 3: pooled HR = 1.80, 95% CI = 1.22 to 2.65). However, clusterin expression was not associated with overall survival in all three groups. Results showed that only the heterogeneity of group 2 was very strong (p = 0.013, I2 = 76.3%), in which the specimens were scored through sCLU staining intensity only. sCLU is a potential biomarker for tumour prognosis, and IHC methods can be more standardised if both intensity and staining proportion are considered.

Testis Tumor of Ovarian Epithelial Type: A Rare Case

Ovarian epithelial type tumors of the testis have been a rare clinical entity. Its awareness and management remain a clinical challenge. We described the case of an 18-year-old, obese male patient who presented with scrotal enlargement. He underwent eversion of tunica vaginalis and resection of epididymal mass. The histology of the resected sample showed an ovarian epithelial type borderline tumor. We believe our case helps to strengthen awareness and management of this rare disease.

CD151 promotes cell metastasis via activating TGF-β1/Smad signaling in renal cell carcinoma

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.

MicroRNA‑126 inhibits proliferation and metastasis in prostate cancer via regulation of ADAM9

The aberrant expression of microRNAs (miRs) has been identified to serve a crucial role in tumor progression. The present study aimed to evaluate the role of miR-126 in human prostate cancer (PCa). Firstly, miR-126 expression in prostate cancer tissues and cell lines was analyzed. A luciferase reporter assay and a rescue assay were performed, which identified ADAM metalloproteinase domain 9 (ADAM9) as the target gene of miR-126. Subsequently, Kaplan-Meier and log-rank analyses were used to investigate the association between ADAM9 expression and PCa prognosis. The results revealed that miR-126 expression was significantly downregulated in PCa tissues and cell lines. miR-126 overexpression was demonstrated to reduce PCa cell proliferation and metastasis, and to reverse the epithelial-mesenchymal transition process in vitro. In addition, as the target gene of miR-126, the upregulation of ADAM9 reestablished cell functions, including cell proliferation, migration and invasion. Patients with high ADAM9 expression levels exhibited a shorter biochemical recurrence-free survival time. In summary, miR-126 serves a role in the proliferation and metastasis of PCa cells, indicating that miR-126 and ADAM9 may represent potential biomarkers in the progression of advanced PCa, in addition to therapeutic targets.