KRT80 expression works as a biomarker and a target for differentiation in gastric cancer.

Keratin 80 (KRT80) is a filament protein that participates in cell differentiation and the integrity of the epithelial barrier. Here, KRT80 expression was higher in gastric cancer compared with normal mucosa at both mRNA and protein levels by bioinformatic analysis, qRT-PCR and Western blot (p<0.05), however, the methylation of KRT80 was lower than in normal mucosa (p<0.05). There was a negative relationship between promoter methylation and expression level of KRT80 gene in gastric cancer (p<0.05). KRT80 mRNA and protein expression was positively correlated with the differentiation of gastric cancer (p<0.05), while KRT80 methylation was negatively associated with gastric cancer differentiation and p53 mutation (p<0.05). The expression of KRT80 mRNA was positively linked to the short survival time of gastric cancers (p<0.05). The differential genes of KRT80 mRNA were involved in ligand-receptor interaction, estrogen signal pathway, peptidase, filament and cytoskeleton, keratinocyte differentiation, vitamin D receptor, muscle contraction, and B cell-mediated immunity (p<0.05). KRT80-related genes were classified into cell adhesion and junction, cadherin binding, skin and epidermis development, and so forth (p<0.05). KRT80 knockdown suppressed proliferation, anti-apoptosis, anti-pyroptosis, migration, invasion and epithelial-mesenchymal transition in gastric cancer cells (p<0.05). These findings indicated that up-regulated expression of KRT80 played a crucial part in gastric carcinogenesis, and might be considered as a biological marker for aggressive behaviors and poor prognosis. Its silencing might be used as an approach of target therapy for gastric cancer patients.

The roles of BTG1 mRNA expression in cancers: A bioinformatics analysis.

BTG1 (B-cell translocation gene 1) may inhibit proliferation and cell cycle progression, induce differentiation, apoptosis, and anti-inflammatory activity. The goal of this study was to clarify the clinicopathological and prognostic significances of BTG1 mRNA expression and related signal pathways in cancers. Using the Oncomine, TCGA (the cancer genome atlas), xiantao, UALCAN (The University of ALabama at Birmingham Cancer data analysis Portal), and Kaplan-Meier plotter databases, we undertook a bioinformatics study of BTG1 mRNA expression in cancers. BTG1 expression was lower in gastric, lung, breast and ovarian cancer than normal tissue due to its promoter methylation, which was the opposite to BTG1 expression. BTG1 expression was positively correlated with dedifferentiation and histological grading of gastric cancer (p < 0.05), with squamous subtype and young age of lung cancer (p < 0.05), with infrequent lymph node metastasis, low TNM staging, young age, white race, infiltrative lobular subtype, Her2 negativity, favorable molecular subtyping, and no postmenopause status of breast cancer (p < 0.05), and with elder age, venous invasion, lymphatic invasion, and clinicopathological staging of ovarian cancer (p < 0.05). BTG1 expression was negatively correlated with favorable prognosis of gastric, lung or ovarian cancer patients, but the converse was true for breast cancer (p < 0.05). KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis showed that the top signal pathways included cytokine-cytokine receptor interaction, cell adhesion molecules, chemokine, immune cell receptor and NF (nuclear factor)-κB signal pathways in gastric and breast cancer. The top hub genes mainly contained CD (cluster of differentiation) antigens in gastric cancer, FGF (fibroblast growth factor)-FGFR (FGF receptor) in lung cancer, NADH (nicotinamide adenine dinucleotide): ubiquinone oxidoreductase in breast cancer, and ribosomal proteins in ovarian cancer. BTG1 expression might be employed as a potential marker to indicate carcinogenesis and subsequent progression, even prognosis.

The clinicopathological significances and related signal pathways of BTG3 mRNA expression in cancers: A bioinformatics analysis.

B cell transposition gene 3 (BTG3) is reported to be a tumor suppressor and suppresses proliferation and cell cycle progression. This study aims to analyze the clinicopathological and prognostic significances, and signal pathways of BTG3 mRNA expression in human beings through bioinformatics analysis. We analyzed BTG3 expression using Oncomine, TCGA (the cancer genome atlas), Xiantao, UALCAN (The University of ALabama at Birmingham Cancer data analysis Portal) and Kaplan-Meier plotter databases. Down-regulated BTG3 expression was observed in lung and breast cancers, compared with normal tissues (p < 0.05), but not for gastric and ovarian cancer (p < 0.05). The methylation of BTG3 was shown to be adversely correlated with its mRNA expression (p < 0.05). BTG3 expression was higher in gastric intestinal-type than diffuse-type carcinomas, G1 than G3 carcinomas (p < 0.05), in female than male cancer patients, T1-2 than T3-4, and adenocarcinoma than squamous cell carcinoma of lung cancer (p < 0.05), in invasive ductal than lobular carcinoma, N0 than N1 and N3, TNBC (triple-negative breast cancer) than luminal and Her2+, and Her2+ than luminal cancer of breast cancer (p < 0.05), and G3 than G2 ovarian carcinoma (p < 0.05). BTG3 expression was positively related to the survival rate of gastric and ovarian cancer patients (p < 0.05), but not for breast cancer (p < 0.05). KEGG and PPI (protein-protein interaction) analysis showed that the BTG3 was involved in cell cycle and DNA replication, digestion and absorption of fat and protein, spliceosome and ribosome in cancer. BTG3 expression was positively linked to carcinogenesis, histogenesis, and aggressive behaviors, and was employed to evaluate the prognosis of cancers by regulating cell cycle, metabolism, splicing and translation of RNA.