The New Role of HNF1A-NAS1/miR-214/INHBA Signaling Axis in Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer and one of the leading causes of death worldwide. Seriously threatens human life and health. Previous studies have identified that inhibin ßA (INHBA) could induce tumorgenesis and progression of CRC through the regulation of the TGF-ß/Smad signal axis. The abnormal expression of INHBA is related to the poor prognosis of patients. The aim of this study was to identify the molecular mechanism of HNF1A-AS1 and miR-214 regulating INHBA and carcinogenesis through bioinformatics combined with experiments. METHODS: The expression of HNF1A-AS1, miRNA-214-5p, INHBA in pan-cancer and CRC were investigated in the Cancer Genome Atlas (TCGA). The correlation between HNF1A-AS1 and immune-related genes or miRNAs was explored via the Gene Expression Profiling Interactive Analysis (GEPIA) and volcano plots, respectively. The association between HNF1A-AS1 and differentially expressed miRNAs was constructed by TargetScan. The miRDB, miRWalk, and TargetScan databases were utilized to predict the target genes of hsa-miR-214. The expression of INHBA in tissues and cell lines of CRC was examined by RT-qPCR and western blot assay. RESULTS: The INHBA and HNF1A-AS1 expressions were increased in Colon adenocarcinoma (COAD) and Rectum adenocarcinoma (READ) of the TCGA database. Hsa-miR-214 was relatively less expressed in CRC tissues compared with para-cancer tissues. The expression of HNF1A-AS1 was negatively correlated with hsa-miR-214. INHBA was one of the target genes of hsa-miR-214 based on miRDB, miRWalk, and TargetScan databases. The specific binding sites of INHBA-3'UTR and miR-214-5p were identified by starBase. The expression level of INHBA was positively correlated with the T stage of tumor and negatively correlated with overall survival (OS) and disease-free survival (DFS) in CRC patients. The results of RT-qPCR and western blot indicated that the expression of INHBA in tissues and cell lines in CRC was higher than those in para-carcinoma tissues and normal colon cell lines, respectively. CONCLUSIONS: These findings suggested that HNF1A-AS1 and miRNA-214-5p were key upstream non-coding RNAs of INHBA. The HNF1A-AS1/miR-214/INHBA signal axis plays a significant role in the tumorgenesis and progression of CRC. By interfering with HNF1A-AS1 and INHBA genes on HT29 and SW480 cells, it was found that HNF1A-AS1 and INHBA genes may be important target genes in CRC.

Efficacy and safety of the "watch-and-wait" approach for rectal cancer with clinical complete response after neoadjuvant chemoradiotherapy: a meta-analysis.

BACKGROUND: Watch-and-Wait (WW) approach is positioned at the cutting edge of non-invasive approach for rectal cancer patients who achieve clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT). This meta-analysis aimed to compare the clinical, oncologic, and survival outcomes of WW versus radical surgery (RS) and to evaluate the efficacy, safety, and possible superiority of WW. METHODS: A systematic search for studies comparing WW with RS was conducted on MEDLINE, Ovid, Embase, Cochrane Library, and Web of Science databases. After screening for inclusion, data extraction, and quality assessment, statistical analysis was performed using Stata/SE14.0 software. Permanent colostomy (PC), local recurrence (LR), distant metastasis (DM), cancer-related death (CRD), 2-, 3-, and 5-year disease-free survival (DFS), and overall survival (OS) were analyzed using fixed effects or random-effects models depending on the heterogeneity. RESULTS: Fourteen studies with moderate-high quality involving 1254 patients were included. Of these, 513 patients were managed with WW and 741 patients were subjected to RS. Compared to RS group, WW group had higher rate of LR (odds ratio OR = 11.09, 95% confidence interval CI = 5.30-23.20, P = 0.000), 2-year OS, and 3-year OS and had lower rate of PC (OR = 0.12, 95% CI = 0.05-0.29, P = 0.000). There were no significant between-group differences with respect to DM, CRD, 2-, 3-, and 5-year DFS (OR = 0.92, 95% CI = 0.81-1.03, P = 0.153), or 5-year OS (OR = 1.01, 95% CI = 0.28-3.63, P = 0.988). CONCLUSION: The WW is a promising treatment approach and is a relatively safe alternative to RS for managing patients with rectal cancer who achieve cCR after nCRT. However, this modality requires rigorous screening criteria and standardized follow-up. Large-scale, multicenter prospective randomized controlled trials are warranted to further verify the outcomes of WW approach.

Construction and validation of a three-microRNA signature as prognostic biomarker in patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), a common type of primary liver cancer, is one of the most aggressive malignant tumors worldwide. Although overall survival (OS) rates for HCC has significantly improved in recent years, however, the exact predictive value of microRNA (miRNA) for the prognosis of HCC has not yet been recognized. Here, we aimed to identify potential prognostic miRNAs involved in HCC by bioinformatics analysis and validated expression levels through quantitative polymerase chain reaction (qPCR) and GEO database. The RNA expression profiles and corresponding clinical information of HCC were available from The Cancer Genome Atlas (TCGA) datasets. Differentially expression and standardization analysis of miRNAs, Kaplan-Meier curve and time dependent ROC curve were performed by using R tools. Differentially expressed miRNAs (DEmiRNAs) and clinical parameters involved in the OS of HCC were confirmed by Cox regression models. And functional enrichment analysis was used to establish functions of the targeted genes of DEmiRNAs. A total of 300 DEmiRNAs were significantly related with HCC, of which 40 were down-regulated and 260 were up-regulated. A total of 344 patients with DEmiRNAs, status, overall survival (OS) time were randomized into training group (172) and test group (172). Multivariate Cox regression analyses revealed that 3 miRNA (hsa-miR-139-3p, hsa-miR-760, hsa-miR-7-5p) had independent prognostic significance for the OS of HCC in both training and test group. Moreover, according to Kaplan Meier analysis, the OS of HCC patients with high-risk score was shorter in validation and entire series. The time dependent ROC curve demonstrated high accuracy of the signature for OS. Besides, target genes of three miRNAs were analyzed by functional enrichment analysis and 20 genes associated with OS were verified by using Kaplan-Meier method. Compared with normal and benign group, the relative expression level of hsa-miR-139-3p was significantly decreased, while hsa-miR-7-5p and hsa-miR-760 were distinctly increased in the plasma of HCC patients. The same results were observed in the independent cohort. Collectively, our research suggested that three-miRNA signature could serve as an independent prognostic indicator for HCC patients.

Novel PI3K/Akt/mTOR pathway inhibitors plus radiotherapy: Strategy for non-small cell lung cancer with mutant RAS gene.

Non-small cell lung cancer (NSCLC) with RAS -mutant gene has been the most difficult obstacle to overcome. Over 25% of muted lung adenocarcinomas have RAS mutation. The prognosis of NSCLC patients with RAS-mutant genes is always poor because there is no effective drug to suppress RAS-mutant genes. NSCLC patients with RAS-mutant usually develop resistance to radiotherapy and chemotherapy, which in some cases leads to a 5-10% survival rate for non-small cell lung cancer (NSCLC). As little clinical symptom of NSCLC was presented at its early stages, thus it always brings in disappointing treatment outcome. Currently, NSCLC presents the highest morbidity and mortality all over the world. The combination of PI3K/AKT/mTOR pathway inhibitors with radiotherapy is a novel strategy to improve radiosensitivity and therapeutic outcome of NSCLC with a RAS-mutant gene. There have been many preclinical studies and clinical trials on the effect of PI3K/AKT/mTOR pathway inhibitors combined with radiotherapy in NSCLC with a RAS-mutant gene have been reported in the past years. This review provides current knowledge of the combination of PI3K/Akt/mTOR pathway inhibitors with radiotherapy, which prove to be a significant improvement for the treatment of NSCLC patients with RAS mutations and will benefit NSCLC patients with RAS mutations.

Short- and long-term outcomes of transanal versus laparoscopic total mesorectal excision for mid-to-low rectal cancer: a meta-analysis.

BACKGROUND AND OBJECTIVES: Transanal total mesorectal excision (TaTME) is positioned at the cutting edge of minimally invasive approach to mid- and low rectal cancer. This meta-analysis was to compare the short- and long-term outcomes of TaTME versus laparoscopic total mesorectal excision (LTME) and to evaluate the safety, efficacy, and possible superiority of TaTME. METHODS: A comprehensive search was conducted for randomized controlled trials (RCTs) and non-RCTs (NRCTs) comparing TaTME with LTME. Inter-group differences were evaluated via standardized mean differences and relative risks (RRs). All outcomes were analyzed using fixed effects or random effects models according to the heterogeneity. Statistical analysis was performed using Stata/SE 12.0 software. RESULTS: Eleven studies (1 RCT and 10 NRCTs) with involving 757 patients were included. Among which, 361 patients underwent TaTME and 396 patients underwent LTME. Comparing the surgical and oncological quality of resection of TaTME with that of LTME, reports of TaTME indicated favorable outcomes considering mesorectal resection quality, circumferential resection margin involvement, intraoperative blood loss, conversions, and postoperative complications, while the differences between the two groups had no statistical significance in terms of distal resection margin, harvested lymph node, operation time, hospital stay, recurrence, 2-year overall survival (OS), and 2-year disease-free survival. CONCLUSION: TaTME is a promising surgical technique and is fully a safe, efficacious, and diffusible alternative to LTME in managing mid- and distal rectal cancer. Larger scale, national, multicentric RCTs are warranted to further verify these results and the possible superiority of TaTME.