OTUB2 Regulates YAP1/TAZ to Promotes the Progression of Esophageal Squamous Cell Carcinoma.

OBJECTIVE: The effects of Otubain-2 (OTUB2) on the proliferation, invasion, and migration of esophageal squamous cell carcinoma (ESCC) were investigated by interfering with OTUB2 expression. METHODS: Bioinformatics analysis was used to analyze OTUB2 expression in esophageal carcinoma and interactions between OTUB2 and YAP1/TAZ. Paraffin-embedded ESCC tissues (n = 183) were selected for immunohistochemical staining to detect OTUB2, YAP1, TAZ, CTGF and their relationship with clinicopathological parameters, then the survival prognosis of ESCC patients was analyzed. Immunofluorescence, western blotting, and qRT-PCR were used to evaluate OTUB2 in ESCC cell lines. Cell lines with the highest expression of OTUB2 were transfected with lentivirus to knockdown OTUB2 levels. Changes in KYSE150 cell proliferation, migration, and invasion were measured using CCK-8, wound healing, and clone formation assays. The Transwell test and flow cytometry identified OTUB2 targets and explored roles and mechanisms involved in ESCC. Effects of OTUB2 on YAP1/TAZ signaling were also observed. RESULTS: Bioinformatics analysis revealed OTUB2 was highly expressed in esophageal cancer and was associated with YAP1/TAZ. Immunohistochemistry showed that OTUB2 expression was increased in ESCC samples compared to parcancerous tissue. YAP1 and TAZ were higher expression in ESCC tissues, mainly localized in the nucleus. Compared with controls, the proliferation, migration, and invasion ability of KYSE150 cells after OTUB2 knockdown were significantly reduced (P < 0.05). The protein expression levels of YAP1, TAZ and CTGF decreased after knocking down the expression of OTUB2 (P < 0.05). OTUB2 knockdown in ESCC cell lines suppressed YAP1/TAZ signaling. CONCLUSIONS: OTUB2 regulated the protein expression of YAP1/TAZ to promote cell proliferation, migration, invasion, and tumor development. Therefore, OTUB2 may represent a biomarker for ESCC and a potential target for ESCC treatment.

Clinical significance of YAP1 and TAZ in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal cancer is the eighth most frequent and sixth most fatal cancer worldwide. This study aimed to investigate the clinical characteristics and prognostic significance of yes related protein 1 (YAP1) and transcriptional co-activator with PDZ binding motif (TAZ) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: A total of 306 ESCC pathological specimens and adjacent tissues (as control; tissues from the esophageal mucosa >5 cm from the edge of the tumor) were collected between January, 2008 and December, 2018. Immunohistochemical staining was used to assess the expression of YAP1 and TAZ proteins in the ESCC and adjacent tissues, and their relationship with clinicopathological parameters was evaluated using SPSS 21.0 software. RESULTS: YAP1 and TAZ proteins were highly expressed in ESCC, and their expression was closely related to TNM stage and lymph node metastasis. Expression of YAP1 was associated with tumor size (P = .029), differentiation (P = .000), depth of invasion (P = .001), and TNM stage (P = .000). Expression of TAZ was associated with tumor size (P = .034), differentiation (P = .000), depth of invasion (P = .029), lymph node metastasis (P = .006), and ethnicity (P < .001). The expression of YAP1 protein was positively correlated with the expression of TAZ protein (r = 0.257, P < .05). YAP1 and TAZ expression (P = .039 and .000, respectively), tumor size (P = .041), and lymph node metastasis (P = .001) significantly affected the overall survival of patients with ESCC, and represent independent factors for overall survival. CONCLUSION: YAP1 and TAZ proteins are highly expressed in ESCC, and closely related to the clinical and pathological parameters such as the diameter of the tumor, degree of differentiation, and depth of invasion, indicating that YAP1 and TAZ may be involved in the development of ESCC. YAP1 and TAZ may be used as prognostic markers in ESCC.

Effectiveness of neoadjuvant chemotherapy on the survival outcomes of patients with resectable non-small-cell lung cancer: A meta-analysis of randomized controlled trials.

PURPOSE: To determine the effectiveness of neoadjuvant chemotherapy (NACT) versus primary surgery on survival outcomes for resectable non-small-cell lung cancer (NSCLC) using an approach based on a meta-analysis. METHODS: The PubMed, EmBase, Cochrane library, and CNKI databases were systematically browsed to identify randomized controlled trials (RCTs) which met a set of predetermined inclusion criteria throughout January 2020. Hazard ratios (HRs) were applied for the pooled overall survival (OS) and progression-free survival (PFS) values, and the pooled survival rates at 1-year and 3-year were used as the relative risk (RR). All the pooled effect estimates with 95% confidence intervals (CIs) were calculated using the random-effects model. RESULTS: Nineteen RCTs contained a total of 4372 NSCLC at I-III stages was selected for final meta-analysis. We noted NACT was significantly associated with an improvement in OS (HR: 0.87; 95%CI: 0.81-0.94; P < 0.001) and PFS (HR: 0.86; 95%CI: 0.78-0.96; P = 0.005). Moreover, the survival rate at 1-year (RR: 1.07; 95%CI: 1.02-1.12; P = 0.007) and 3-year (RR: 1.16; 95%CI: 1.06-1.27; P = 0.001) in the NACT group was significantly higher than the survival rate for the primary surgery group. Finally, the treatment effects of NACT versus primary surgery on survival outcomes might be different when stratified by the mean age of patients and the tumor stages. CONCLUSIONS: NACT could improve survival outcomes for patients with resectable NSCLC, suggesting its suitable future applicability for clinical practice. However, large-scale RCT should be conducted to assess the chemotherapy regimen on the prognosis of resectable NSCLC.