Fibronectin 1 (FN1) is involved in the occurrence and development of various tumors and is upregulated in multiple cancer types. FN1 has been demonstrated to promote cell proliferation and migration in gastric cancer cell lines. However, the relationship between the expression of FN1 and clinicopathological factors and prognosis is not clear in gastric cancer (GC). The aim of the present study was to investigate the association between FN1 expression and clinicopathology and prognosis of gastric cancer. In this study, 17 publicly available GC cohorts (n=2,376) with gene expression data from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and Oncomine databases were tested. In addition, FN1 protein expression was validated by immunohistochemistry in a separate cohort (n=190). The meta-analysis results demonstrated an increase in FN1 expression at the protein and mRNA level in GC tissues, and the FN1 gene was highly expressed at the mRNA level in the advanced T stage (T2 + T3 + T4) group compared with that in the early T stage (T1) group. In addition, the expression of epithelial FN1 at the protein level was positively correlated with tumor size. FN1 expression at the protein and mRNA level was a predictor of poor prognosis following radical resection of GC. In conclusion, the expression of FN1 in GC tissues is upregulated compared with adjacent normal tissues, and it is a potential biomarker of poor prognosis in patients with GC.

Background: Aberrant transcript alternative splicing is an important regulatory process closely connected with oncogenesis. Purpose: The objective of this study was to determine the phenotype and function of a novel long noncoding RNA (lncRNA) LINC00477 in gastric cancer. Patients and methods: The gastric cancer samples of 140 from Oncomine database and 17 from our own hospital, as well as three gastric cancer cell lines MKN-45, AGS and KATO III were used in this study. The expression of the spliced isoforms of LINC00477 were tested. The tumor effects of LINC00477 on gastric cancer were investigated in vitro and in vivo. The mechanism of LINC00477 interacted with aconitase 1 (ACO1) was further examined by RIP and pull down assay. Results: The overall expression of LINC00477 was reduced in gastric cancers compared to normal gastric tissues. The isoform 1 of LINC00477 was down-regulated while the isoform 2 was up-regulated in gastric cancer cells. The opposite role of isoforms 1 and 2 in the proliferation and migration of cancer cells in vitro and in vivo was observed. Furthermore, isoform 1 of LINC00477 was determined to interact with ACO1 and suppress the conversion ability from citrate to isocitrate by ACO1. Conclusion: we presented the important roles of the spliced isoforms of long noncoding RNA, LINC00477 in gastric carcinogenesis.

Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide, with high incidence and mortality rate. There is an urgent need to identify effective diagnostic and prognostic biomarkers for HCC. Members of the acidic leucine-rich nucleophosphoprotein 32 (ANP32) family, which mainly includes ANP32A, ANP32B, and ANP32E, are abnormally expressed and have prognostic value in certain cancers. However, the diagnostic, prognostic, and therapeutic value of ANP32 family members in HCC has not yet been fully studied. In this study, we identified the diagnostic and prognostic value of ANP32 family members in HCC. Transcriptome data from public databases, such as the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, suggested that ANP32A, ANP32B, and ANP32E were upregulated in HCC tissues, and high expression of ANP32 family members was associated with advanced pathologic stage and histologic grade. Our immunohistochemistry and western blot results further verified the differential expression of ANP32 family members. ANP32A, ANP32B, and ANP32E had an outstanding diagnostic potential. Survival analysis of HCC patients in TCGA databases demonstrated that ANP32A, ANP32B, and ANP32E were associated with poor overall survival (OS) and disease-specific survival (DSS). Univariate and multivariate Cox analyses suggested the capability of ANP32B and ANP32E to independently predict the OS and DSS of HCC patients. Gene set enrichment analysis (GSEA) showed that ANP32 family members were associated with immune response, epidermal cell differentiation, and stem cell proliferation. Expression of ANP32 family members was associated with immune cell infiltration and immune status in the tumor microenvironment of HCC, and patients with high ANP32 family expression had poor sensitivity to immunotherapy. Finally, we identified potential chemotherapy drugs for HCC patients with high ANP32 family expression by CellMiner database. This study suggested the diagnostic, prognostic, and therapeutic roles of the ANP32 family in HCC patients, providing potential therapeutic targets for HCC.

Background: Somatic mutations are strongly linked to cancer. Tumor mutation burden (TMB), PD-L1, and CTLA-4 are considered to be important biomarkers for selecting patients with stomach adenocarcinoma (STAD) for immune checkpoint inhibitors (ICIs) therapy. Nonetheless, whether specific gene mutations are related to prognosis, TMB, sensitivity to ICIs, and tumor-infiltrating immune cells remains unclear.Methods: Mutation data for STAD are derived from the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) database. Mutation data were analyzed by R software to calculate gene mutation frequency and TMB. Kaplan-Meier survival analysis and Log rank test assessed patient prognosis, and univariate and multivariate Cox regression analyses were used to identify independent risk factors. The limma package of R software was used for differential analysis. Gene set enrichment analysis (GSEA) was performed by GSEA4.1.0. TISIDB was used to validate the correlation of OBSCN mutations with immune cell infiltration in STAD TME.Results: 16 genes both mutated in TCGA and ICGC. Although all of the 16 genes mutations are correlated to high TMB, only patients with OBSCN mutation enjoyed a better prognosis in STAD. Univariate and multivariate Cox regression analyses showed that OBSCN mutation was an independent predictor for prognosis in STAD patients. Gene Set Enrichment Analysis showed that OBSCN mutations were mainly related to peroxisome, MTORC1 signaling, and Oxidative phosphorylation. Then, compared with the OBSCN wild type (WT) group, four genes in the OBSCN mutant type (MT) group are up-regulated, and 26 genes are down-regulated. Finally, we observed higher infiltration of T cell follicular helper, NK cells, Th1 cells, Th2 cells, CD8+ T cells, central memory CD8+ T cells, and activated CD4+ T cells but lower mast cells in the OBSCN MT group. Additionally, we found STAD patients with OBSCN mutation are more sensitive to ICIs treatment and certain chemotherapy drugs such as cisplatin, 5-Fluorouracil, and Docetaxel, which are most commonly used for STAD.Conclusions: OBSCN mutations serve as a biomarker for predicting STAD prognosis and sensitivity to ICIs and are associated with anti-tumor immunity.