HIF1A-AS2 Promotes the Proliferation and Metastasis of Gastric Cancer Cells Through miR-429/PD-L1 Axis.

BACKGROUND: Gastric cancer (GC) is a common leading cause of cancer-related mortality of all malignancies. LncRNA hypoxia-inducible factor-1 alpha antisense RNA-2 (HIF1A-AS2) has been identified to involve in the development of GC. Therefore, we further explored the detailed molecular mechanism of HIF1A-AS2 in GC progression. METHODS: The expression of HIF1A-AS2, microRNA-429 (miR-429), and programmed cell death ligand 1 (PD-L1) was measured using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell proliferation, migration, and invasion abilities were detected by Cell Counting Kit-8 (CCK-8) or transwell assay. The interaction between miR-429 and HIF1A-AS2 or PD-L1 was confirmed by luciferase reporter assay. Murine xenograft model was established to investigate the role of HIF1A-AS2 in vivo. RESULTS: HIF1A-AS2 was elevated in GC tissues and cell lines. Functional experiments showed that HIF1A-AS2 knockdown inhibited GC cell proliferation, migration, and invasion in vitro, as well as hindered tumor growth in vivo. Moreover, HIF1A-AS2 directly bound to miR-429 based on bioinformatics prediction and luciferase assay, and inhibition of miR-429 abolished the effects of HIF1A-AS2 knockdown on GC cells. Furthermore, miR-429 directly targeted PD-L1, and overexpression of miR-429 suppressed GC tumorigenesis via PD-L1. Besides that, PD-L1 also performed an oncogenic role in GC cell proliferation and metastasis. Additionally, HIF1A-AS2 could indirectly regulate PD-L1 expression via sponging miR-429. CONCLUSION: HIF1A-AS2 is a dependable predictor of malignancy and prognosis in GC and functions as an oncogene to promote GC cell proliferation and metastasis by regulating miR-429/PD-L1 axis, indicating a new insight into the search for novel biomarkers and therapeutic strategies.

Investigation of microRNA-155 as a serum diagnostic and prognostic biomarker for colorectal cancer.

The aim of the present study was to explore serum microRNA-155 (miR-155) expression in patients with colorectal cancer (CRC) and examined the potential usefulness of this molecule as a biomarker for diagnosis and prognosis in CRC. Serum samples were obtained between May 2007 and March 2013 from 146 CRC patients and 60 healthy controls. Serum miR-155 expression levels were measured by quantitative real time reverse transcription-polymerase chain reaction (qRT-PCR). Survival curves were obtained using the Kaplan-Meier method and assessed by the log-rank test. The receiver operating characteristic (ROC) curve was used for the prediction of cut-off values of the markers. Serum miR-155 expression level on average was upregulated in CRC patients compared with the matched healthy controls (P < 0.001). ROC curve analysis showed that miR-155 was a useful marker for discriminating cases from healthy controls, with an area under the ROC curve (AUC) of 0.776 (95% confidence interval (CI) 0.714 to 0.837, P < 0.001). Kaplan-Meier analysis with the log-rank test indicated that high serum miR-155 expression had a significant impact on overall survival (38.2 vs. 69.9%; P < 0.001) and progression-free survival (34.8 vs. 66.0%; P < 0.001). In conclusion, the detection of miR-155 levels in the serum might serve as a new tumor biomarker in the diagnosis and assessment of prognosis of CRC.

Efficacy and toxicity of adding cetuximab to chemotherapy in the treatment of metastatic colorectal cancer: a meta-analysis from 12 randomized controlled trials.

Cetuxiamb, a monoclonal antibody against epidermal growth factor receptor (EGFR), has been used in combination with chemotherapy for patients with metastatic colorectal cancer (mCRC). However, the efficacy of combined therapies of cetuximab and different chemotherapy regimens remains controversial. Therefore, we conducted a meta-analysis to evaluate the efficacy and toxicity of adding cetuximab to oxaliplatin-based or irinotecan-based chemotherapeutic regimens for the treatment of patients with mCRC with wild-type/mutated KRAS tumors. Randomized controlled trials (RCTs), published in Pubmed and Embase were systematically reviewed to assess the survival benefits and toxicity profile mCRC patients treated with cetuximab plus chemotherapy. Outcomes included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and toxicities. Results were expressed as the hazard ratio (HR) with 95 % confidence intervals (CI). Pooled estimates were generated by using a fixed-effects model or a randomized-effects model, depending on the heterogeneity among studies. A total of 12 trials involving 6,297 patients met the inclusion criteria and were included in this meta-analysis. All patients were administered oxaliplatin-based or irinotecan-based chemotherapy with or without cetuximab. Pooled results showed that the addition of cetuximab did not significantly improve the OS (HR = 0.99, 95 % CI = 0.89-1.09; Z = 0.28, P = 0.78) or PFS (HR = 0.94, 95 % CI = 0.81-1.10; Z = 0.76, P = 0.49), but did improve ORR (RR = 1.34, 95 % CI = 1.08-1.65; Z = 2.72, P = 0.00), when compared with chemotherapy alone. Subgroup analysis showed the highest PFS benefit in patients with wild-type KRAS tumors (HR = 0.80, 95 % CI = 0.65-0.99; Z = 2.1, P = 0.04) or wild-type KRAS/BRAF tumors (HR = 0.64, 95 % CI = 0.52-0.79; Z = 4.15, P = 0.00). When combined with cetuximab, irinotecan-based chemotherapy was significantly associated with prolonged PFS (HR = 0.79, 95 % CI = 0.66-0.96; Z = 2.36, P = 0.02) for all patients with differing gene-status. The incidence of grade 3/4 adverse events, including skin toxicity, diarrhea, hypertension, anorexia, and mucositis/stomatitis, was slightly higher in the combined therapy group than in the chemotherapy-only group. Based on the current evidence, the addition of cetuximab to chemotherapy significantly improves the PFS in patients with wild-type KRAS or wild-type KRAS/BRAF tumors as well as the ORR in all patients. In addition, irinotecan-based combination therapy showed a beneficial effect on the PFS in all patients. These findings confirm the use of cetuximab in combination with chemotherapy for the treatment of patients with mCRC with wild-type KRAS tumors. Further multi-center RCTs are needed to indentify these findings.

Endothelial cell-specific molecule-1: a potential serum marker for gastric cancer.

No ideal serum markers for gastric cancer (GC) screening have been identified. The aim of this study was to determine the usefulness of endothelial cell-specific molecule-1 (ESM-1) as a serum marker for GC. The ESM-1 levels in serum specimens from 114 patients with GC and 55 health subjects were measured using a sandwich ELISA kit. Receiver operating characteristic (ROC) curve was calculated to assess the diagnostic value of ESM-1. Survival curves by the Kaplan-Meier method were plotted to display overall survival distributions. Univariable and multivariable Cox regression analyses were performed to assess independent prognostic factors for overall survival in GC. We showed that the ESM-1 levels in the serum of patients with GC (83.7 ± 16.2 pg/mL) were significantly elevated compared to health subjects (44.7 ± 16.4 pg/mL). The accuracy, sensitivity, and specificity of ESM-1 for GC were 0.946, 98, and 80 %, respectively, by ROC curve analysis. The positive and negative predictive values were 91 and 93.6 %, respectively. The likelihood ratios of a positive or negative test result were 20.9 and 0.14, respectively. When analyzed with a Cox regression model, a higher serum ESM-1 level (≥84.2 pg/mL) was correlated with poor prognosis. This study suggests that serum ESM-1 level is increased in patients with GC and that ESM-1 can be used as a potential serum marker for early detection and prognosis evaluation of GC.

Gastric outlet obstruction caused by heterotopic pancreas: A case report and a quick review.

A 46-year-old Chinese woman presented with nausea, recurrent vomiting, and abdominal pain. Gastroduodenal endoscopic examination revealed an oval-shaped submucosal tumor at the prepyloric area on the posterior wall of the stomach. A degenerated gastrointestinal stromal tumor was suspected. Distal gastrectomy was performed and a histological diagnosis of heterotopic pancreas (HPs) was confirmed. The patient had an uneventful postoperative course and was discharged 7 d after operation. The patient remains healthy and symptom-free in the follow-up of 6 mo. This is a report of a case of gastric outlet obstruction resulting from pancreatic heterotopia in the gastric antrum in an adult woman.

Are there tumor suppressor genes on chromosome 4p in sporadic colorectal carcinoma?

AIM: To study the candidate tumor suppressor genes (TSG) on chromosome 4p by detecting the high frequency of loss of heterozygosity (LOH) in sporadic colorectal carcinoma in Chinese patients. METHODS: Seven fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by PCR. PCR products were electrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. The same procedure was performed by the other six microsatellite markers spanning D4S3013 locus to make further detailed deletion mapping. Comparison between LOH frequency and clinicopathological factors was performed by c2 test. RESULTS: Data were collected from all informative loci. The average LOH frequency on 4p was 24.25%, and 42.3% and 35.62% on D4S405 and D4S3013 locus, respectively. Adjacent markers of D4S3013 displayed a low LOH frequency (< 30%) by detailed deletion mapping. Significant opposite difference was observed between LOH frequency and tumor diameter on D4S412 and D4S1546 locus (0% vs 16.67%, P = 0.041; 54.55% vs 11.11%, P = 0.034, respectively). On D4S403 locus, LOH was significantly associated with tumor gross pattern (11.11%, 0, 33.33%, P = 0.030). No relationship was detected on other loci compared with clinicopathological features. CONCLUSION: By deletion mapping, two obvious high frequency LOH regions spanning D4S3013 (4p15.2) and D4S405 (4p14) locus are detected. Candidate TSG, which is involved in carcinogenesis and progression of sporadic colorectal carcinoma on chromosome 4p, may be located between D4S3017 and D4S2933 (about 1.7 cm).

RETRACTED: The function of long non-coding RNA MT1JP in the development and progression of gastric cancer.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Executive Editor (Chairman) as panels from Figures 3A,B and 4D are similar to panels from Figures 4A,B and 5E of the article published by Mingjun Bi, Hongmei Yu, Bin Huang and Cuiyan Tang in Gene 626 (2017) 337­343 http://dx.doi.org/10.1016/j.gene.2017.05.049. Also, Figures 3C and 4A are similar to Figures 4C and 5A of the Gene article. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. As such this article represents an abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.

Analysis of distinct long noncoding RNA transcriptional fingerprints in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies with the worst prognosis. Recent studies have demonstrated that long noncoding RNAs (lncRNAs) play critical roles in tumorigenesis and cancer progression. However, the expression pattern and roles of lncRNAs in the development of PDAC remain unknown. Herein, we globally analyzed the lncRNA expression profile in human PDAC and non-tumor tissues using four independent public microarray datasets from Gene Expression Omnibus (GEO). The analysis of GEO datasets by repurposing microarray probes confirmed that hundreds of lncRNAs are differentially expressed in PDAC tissues compared with normal tissues. We selected four lncRNAs including LINC00152, CASC9, LINC00226 and F11-AS1 for validation in PDAC cell lines and normal cells. Loss of function assays were performed to investigate the roles of LINC00152 and CASC9 in PDAC cell proliferation and invasion. Taken together, our findings demonstrate lncRNA expression alterations in PDAC and may provide new potential molecular markers for PDAC patient diagnosis and treatment.