Helicobacter pylori-induced protein tyrosine phosphatase receptor type C as a prognostic biomarker for gastric cancer.

BACKGROUND: Helicobacter pylori (H. pylori) infection is closely associated with the tumorigenesis of gastric cancer. The aim of the present study was to identify the key regulator in H. pylori-related gastric cancer and to study the expression level and clinical value of the indicated key regulator in gastric cancer. METHODS: The GSE6143 dataset was used to identify differentially expressed genes (DEGs) with limma R package, and enrichment analysis was done using the Metascape web-based portal. The protein-protein interaction analysis was done using Search Tool for the Retrieval of Interacting Genes/Proteins. Gastric adenocarcinoma AGS and BGC-823 cells were treated with H. pylori strain 26695 to construct the in vitro H. pylori infection model, and quantitative reverse transcription polymerase chain reaction was used to analyze the mRNA levels of indicated genes. The correlation analysis between two genes in gastric cancer was done by GEPIA. Furthermore, the PTPRC expression by pathological features analysis was conducted in UALCAN, an easy to use, interactive web-portal (http://ualcan.path.uab.edu). The survival analysis for gastric cancer, based on PTPRC expression levels, was done using the Kaplan-Meier plotter. RESULTS: DEGs in gastric mucosa with or without H. pylori infection were identified and enriched in immune-related pathways and cancer pathways. The protein-protein interaction analysis confirmed the enrichment analysis of gene ontology. H. pylori strain 26695 exposure also confirmed the alteration of gene expression levels in AGS and BGC-823 cells. PTPRC was co-expressed with CSF2RB and TNFRSF7, indicating a significant positive correlation in gastric cancer. PTPRC was overexpressed in gastric cancer, and the overexpression of PTPRC was positively correlated with the progression of gastric cancer. Furthermore, the high expression of PTPRC could act as a poor prognostic factor for gastric cancer patients, especially for those at advanced stage. CONCLUSIONS: H. pylori-induced PTPRC is overexpressed in gastric cancer, and the overexpression of PTPRC is positively associated with the development of gastric cancer. The high expression of PTPRC could serve as poor prognostic biomarker for gastric cancer patients, especially for those at advanced stage. H. pylori-induced PTPRC is a prognostic biomarker for gastric cancer.

Systemic inflammatory response predicts poor prognoses in Barcelona Clinic Liver Cancer stage B/C hepatocellular carcinoma with transarterial chemoembolization: a prospective study.

BACKGROUND: Chronic inflammation has been demonstrated to be an important factor in the initiation, promotion, and progression of hepatocellular carcinoma (HCC). The aim of this study was to investigate the prognostic values of systemic inflammation markers in Barcelona Clinic Liver Cancer (BCLC) stage B/C HCC. METHODS: A prospective non-randomized study was performed from June 2016 to May 2017; 51 of 123 BCLC stage B/C HCC patients were enrolled and received transarterial chemoembolization (TACE). Clinical and laboratory data were recorded. Serum IL-6, IL-10, C-reactive protein (CRP), and blood-neutrophil-to-lymphocyte ratio (NLR) levels were analyzed during the perioperative period. Patient prognosis was investigated. Twenty-eight stage A cases and 10 stage B/C patients who received resection were also collected as controls. RESULTS: Compared to the stage A group, the BCLC stage B/C HCC patients had significantly higher serum IL-6, CRP, and blood NLR levels. Serum IL-6, IL-10, CRP, and blood NLR levels increased significantly 3 days after treatment (TACE/resection) and returned to baseline levels after 30 days. By univariate analyses, tumor size, high pretreatment serum IL-6, CRP, and blood NLR levels predicted worse progression-free survival (PFS) after TACE (log-rank test P<0.001, P=0.007, P=0.001, respectively). Multivariate analysis revealed that both high serum IL-6 (P=0.018) and CRP (P=0.042) were independent predictors of worse PFS, meanwhile blood NLR was the only inflammatory factor associated to overall survival (OS) (P=0.046). CONCLUSIONS: Serum IL-6, CRP, and blood NLR levels were significantly elevated in stage B/CHCC. Serum IL-6 and CRP were independent predictors of poor PFS while NLR independently predicted worse OS in BCLC stage B/C HCC.

Correction: Posttranscriptional regulation of Galectin-3 by miR-128 contributes to colorectal cancer progression.

[This corrects the article DOI: 10.18632/oncotarget.14839.].

Validation of the chinese version of the EORTC QLQ-CR29 in patients with colorectal cancer.

AIM: To assess the validity and reliability of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal Cancer 29 (EORTC QLQ-CR29) in Chinese patients with colorectal cancer (CRC). METHODS: From March 2014 to January 2015, 356 patients with CRC from four different hospitals in China were enrolled in the study, and all patients self-administered the EORTC QLQ-CR29 and the quality of life core questionnaire (EORTC QLQ-C30). Evaluation of the scores was based on the Karnofsky Performance Scale (KPS). The reliability and validity of the questionnaires were assessed by Cronbach's α coefficient, the Spearman correlation test and Wilcoxon rank sum test. RESULTS: The EORTC QLQ-CR29 showed satisfactory reliability (α > 0.7), although the urinary frequency and blood and mucus in stool dimensions had only moderate reliability (α = 0.608). The multitrait scaling analyses showed good convergent (r > 0.4) and discriminant validity. Significant differences were obtained for each item in the different KPS subgroups (KPS ≤ 80; KPS > 80). Body image and most single-item dimensions showed statistically significant differences in patients with a stoma compared with the rest of the patients. CONCLUSION: The EORTC QLQ-CR29 exhibits high validity and reliability in Chinese patients with CRC, and can therefore be recommended as a valuable tool for the assessment of quality of life in these patients.

Posttranscriptional regulation of Galectin-3 by miR-128 contributes to colorectal cancer progression.

Here we demonstrated that Galectin-3 protein level was frequently up-regulated in colorectal cancer (CRC) cells and tissues. Galectin-3 up-regulation correlated with CRC progression and predicted a shorter overall survival of CRC patients. Galectin-3 overexpression attenuated the chemo-sensitivity of cancer cells, but enhanced the potential invasiveness. To explore the mechanism for Galectin-3 dysregulation, we found that miR-128 level was frequently down-regulated in CRC and negatively correlated with Galectin-3 level. Using bioinformatics analysis and experimental validation, we showed that miR-128 could directly target Galectin-3 to repress its protein level. MiR-128 decrease associated with CRC progression and predicted a worse overall survival of CRC patients. Ectopic miR-128 expression enhanced the chemo-sensitivity of CRC cells in vitro and in vivo, and inhibited the potential invasiveness. Galectin-3 expression impaired the cancer suppressive effects of miR-128. These data highlighted the role of miR-128/Galectin-3 axis in colorectal cancer.

HabibTM 4X-assisted resection versus clamp-crush resection for hepatocellular carcinoma: a propensity-matching study.

Long term outcome of ablation-assisted hepatic resection is unclear for hepatocellular carcinoma (HCC) patients. This study was scheduled to compare the outcome of Habib 4X ablation assisted resection (Habib group) with clamp-crush resection (CC group) for HCC. In this study, we retrospectively enrolled 81 patients from the Habib group and 103 patients from the CC group. Oncologic outcomes were analyzed using a propensity score matching (PSM) method. Compared with the CC group, the Habib group had higher levels of γ-glutamyltransferase (P=0.044) and albumin (P=0.001), larger tumor sizes (P=0.007), shorter operation times (P=0.001), less blood loss (P=0.005), and less blood transfusions (P=0.038). There were no significant differences in complications (P=0.310), recurrence-free survival rates (RFS, P=0.112), or overall survival rates (OS, P=0.203) between the two groups. For the 67 patient pairs selected from the PSM analysis, the Habib group had better RFS and OS (P=0.033 and P=0.014, respectively). A Cox proportional hazards analysis revealed that Habib-assisted resection was an independent factor for RFS and OS (P=0.008 and P=0.016, respectively). Furthermore, for the 42 patients with central and large tumors, the Habib group had better RFS and OS than the CC group (P=0.035 and P=0.038, respectively). However, the differences of RFS and OS (P=0.117 and P=0.126, respectively) were not significant among 92 patients with peripheral or small tumors. Hence, HabibTM 4X-assisted resection is safe and provides better survival for HCC patients, particularly those with central and large tumors.

miR-222/VGLL4/YAP-TEAD1 regulatory loop promotes proliferation and invasion of gastric cancer cells.

Gastric cancer (GC) is one of the most common malignant tumors and recent data demonstrates the tumor suppressor role of VGLL4 in GC, but the mechanisms for VGLL4 downregulation in GC remain to be elucidated. Here, we confirmed the suppressor role of VGLL4 on proliferation and invasion in GC cells with over-activated YAP-TEAD signal, and indicated the reverse correlation between expression patters of VGLL4 and miR-222. Bioinformatics analysis combined with experimental confirmation revealed VGLL4 is a direct target of miR-222 in GC cells. Functionally, miR-222 inhibitor significantly inhibited GC cells proliferation and invasion and VGLL4 knockdown abolished the effects of miR-222 inhibitor. Moreover, TEAD1 knockdown resulted in decrease of miR-222 expression and increase of VGLL4 expression, and also resulted in reduction of luciferase activity driven by miR-222 promoter in GC cells, suggesting over-activated TEAD1 positively feedback transcriptionally regulates miR-222 expression via physically binding to the miR-222 promoter indicated by ChIP assay. Collectively, our findings implied the important role of miR-222/VGLL4/YAP-TEAD1 regulatory loop maintaining over-activated YAP-TEAD1 signal in GC cells, and enriched the rationale of VGLL4 in GC based on which a promising therapeutic strategy will be developed.

Esophagogastrostomy plus gastrojejunostomy: a novel reconstruction procedure after curative resection for proximal gastric cancer.

OBJECTIVE: The choice of surgical strategy for patients with proximal gastric cancer remains controversial. In this study, we recommend that a new reconstruction procedure be performed following proximal gastrectomy. METHODS: We conducted a retrospective study involving 71 patients who underwent gastrectomy for proximal gastric cancer. Clinicopathological features, postoperative complications, nutritional status, and overall survival (OS) rate were compared among three different reconstruction approaches. RESULTS: There were 34 cases of proximal gastrectomy followed by esophagogastrostomy reconstruction (EG), 16 cases of total gastrectomy and Roux-en Y reconstruction (RY) and 21 cases of proximal gastrectomy followed by esophagogastrostomy plus gastrojejunostomy reconstruction (EGJ). Though the clinicopathological features, the nutritional status and OS rate were similar among the three groups of patients, the incidence of reflux esophagitis was significantly higher in the EG group (35.3%) than the RY (6.2%) and EGJ (9.6%) groups(P < 0.05). Few EGJ patients suffered from either reflux esophagitis or anastomotic stenosis. CONCLUSIONS: The EGJ reconstruction method helps to resolve the syndrome of reflux esophagitis. Our data indicates that it is a simple, safe, and effective reconstruction procedure for PGC.