Sheng Xu

Background: SIVA-1 has been reported to play a key role in cell apoptosis and gastric cancer (GC) chemoresistance in vitro. Nevertheless, the clinical significance of SIVA-1 in GC chemotherapy remains unclear.

Background: Several studies give a superficial description that HEPACAM family member 2 (HEPACAM2) seems to be a prognostic biomarker in colon adenocarcinoma (COAD). While, systematic and in-depth research about diagnostic and prognostic value of HEPACAM2 in COAD patients is lacked. Besides, relationship between HEPACAM2 gene expression levels and immune cell infiltration is unclear. Methods: Firstly, we analyzed the differential expression levels of HEPACAM2 gene and diagnostic value from different databases. Secondly, a cohort of Guangxi COAD patients was established to verify HEPACAM2 expression pattern and diagnostic value. Thirdly, univariate and multivariate survival analysis of the prognostic value of HEPACAM2 gene in patients with COAD was performed. We also utilized joint-effects analysis and comprehensive prognosis analysis to investigate the prognostic value of HEPACAM2 and related genes. Finally, we explored the relationship between HEPACAM2 gene expression levels and immune cell infiltration.Results: In several biological databases, HEPACAM2 mRNA expression level in COAD tumor tissues was significantly lower than that of adjacent normal tissues. The diagnostic ROC curve results indicated that HEPACAM2 gene had a high diagnostic value in COAD. The qPCR verification results in the Guangxi cohort showed that HEPACAM2 expression level in COAD tumor tissues was significantly lower than that of adjacent normal tissues (PHEPACAM2 gene had a poorer overall survival (OS) in COAD patients when compared with those with high expression ((P = 0.038, HR (95% CI) = 0.635(0.414-0.976)). Joint-effects analysis and comprehensive prognosis analysis showed that high expression of HEPACAM2 combined with high expression of CLCA1, high expression of REP15, and high expression of B3GNT6 were associated with a better overall survival of COAD.Conclusion: This study suggested that the HEPACAM2 may be a diagnostic and prognostic biomarker for COAD. Besides, HEPACAM2 was involved with immune response progress, Chemokine signaling pathway, Ras signaling pathway and Hematopoietic cell lineage.

Siva‑1 is a well‑known anti‑apoptosis protein that serves a role in multiple types of cancer cells. However, whether Siva‑1 affects multidrug resistance via the NF‑κB pathway in gastric cancer is currently unknown. The present study aimed to determine the possible involvement of Siva‑1 in gastric cancer anticancer drug resistance in vitro. A vincristine (VCR)‑resistant KATO III/VCR gastric cancer cell line with stable Siva‑1 overexpression was established. The protein expression levels of Siva‑1, NF‑κB, multidrug resistance 1 (MDR1) and multidrug resistance protein 1 (MRP1) were detected via western blotting. The effect of Siva‑1 overexpression on anticancer drug resistance was assessed by measuring the 50% inhibitory concentration of KATO III/VCR cells to VCR, 5‑fluorouracil and doxorubicin. The rate of doxorubicin efflux and apoptosis were detected by flow cytometry. Additionally, colony formation, wound healing and Transwell assays were used to detect the proliferation, migration and invasion of cells, respectively. The results of the current study revealed that the Siva‑1‑overexpressed KATO III/VCR gastric cancer cells exhibited a significantly decreased sensitivity to VCR, 5‑fluorouracil and doxorubicin. The results of flow cytometry revealed that the percentage of apoptotic cells decreased following overexpression of Siva‑1. The colony formation assay demonstrated that cell growth and proliferation were significantly promoted by Siva‑1 overexpression. Additionally, Siva‑1 overexpression increased the migration and invasion of KATO III/VCR cells in vitro. Western blot analysis determined that Siva‑1 overexpression increased NF‑κB, MDR1 and MRP1 levels. The current study demonstrated that overexpression of Siva‑1, which functions as a regulator of MDR1 and MRP1 gene expression in gastric cancer cells via promotion of NF‑κB expression, inhibited the sensitivity of gastric cancer cells to certain chemotherapies. These data provided novel insight into the molecular mechanisms of gastric cancer, and may be of significance for the clinical diagnosis and therapy of patients with gastric cancer.

We hypothesize that adrenal insufficiency in acute necrotizing pancreatitis (ANP) is attributable to hemorrhagic inflammation, necrosis, and apoptosis of the adrenal cortex. Arguments to support this view are presented in the study that investigated morphological and functional changes of adrenal and the distinct roles of inflammatory mediator secretory phospholipase A₂ (sPLA₂) and apoptosis-related genes Bax and Bcl-2 played in acute adrenal injury in ANP. After ANP model was induced, pancreatic histology, serum amylase, sPLA₂, and corticosterone were analyzed. The adrenal morphology, apoptotic cells by TUNEL assay, and ultrastructures were observed. sPLA₂-IIA and Bcl-2 and Bax expressions were detected by immunohistochemistry. Histopathologic grading of adrenal was higher in ANP group than in controls. Serum corticosterone was stimulated to maximal level at 3 h, then dropped to the bottom at 24 h (P < 0.05). Apoptotic index, sPLA2-IIA, and Bax expression were increased steeply after pancreatitis, and the Bax/Bcl-2 ratio was elevated gradually (P < 0.05). Sustained decrease in serum corticosterone level following adrenal injury during ANP appears to be, in part, due to the crucial roles of inflammation and apoptosis in adrenal cortex. These findings could suggest that sPLA2, Bax, and Bcl-2 may be involved in the course of adrenal injury after ANP.