Expression and prognostic value of prohibitin in gastrointestinal cancers based on bioinformatics

Objective To explore the expression of prohibitin (PHB) in tumor tissues and analyze its effect on the prognosis of patients with digestive system malignant tumor (DT) and its mechanism. Methods ① The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database were used to compare the expression of PHB in tumor tissues and normal tissues.②Five pairs of gastric cancer and adjacent tissues and 5 pairs of colon cancer and adjacent tissues were collected, and RT-qPCR was used to verify the mRNA expression levels.③RT-qPCR and Western blotting were used to verify the differential expression of PHB in normal gastric mucosa cells (GES-1), gastric cancer cells (AGS, MKN45 and HGC27), normal colon cells NCM-460 and human colon cancer cell line SW480.④R language was used to analyze the effect of PHB on the prognosis, tumor microenvironment, tumor mutation burden and microsatellite instability of DT patients.⑤CIBERSORT algorithm was used to study the correlation between PHB expression in tumor tissues and tumor immune cell infiltration.Gene Set Enrichment Analysis (GSEA) was used to explore the biological function of PHB.⑥R language was used to analyze the relationship between PHB and drug sensitivity. Results ① PHB was highly expressed in colon cancer, cholangiocarcinoma, esophageal cancer, liver cancer, rectal cancer and gastric cancer (P < 0.01).②RT-qPCR and Western blotting showed that PHB was highly expressed in the tissues and cell lines of gastric cancer (P < 0.01) and colon cancer (P < 0.01).③The differential expression of PHB was associated with poor prognosis of hepatocellular carcinoma (P=0.002).In cholangiocarcinoma, gastric cancer, pancreatic cancer, liver cancer and esophageal cancer, PHB was positively correlated with tumor mutation burden and microsatellite instability (P < 0.05).④PHB was positively correlated with M2 macrophages in colon cancer (P=0.03).In cholangiocarcinoma, it was positively correlated with activated CD4+ memory T cells (P < 0.05).In esophageal carcinoma, it was positively correlated with activated hypertrophy (P=0.03).It was positively correlated with M0 and M2 macrophages and monocytes in hepatocellular carcinoma (P < 0.05).It was positively correlated with resting dendritic cells, eosinophils and activated CD4+ memory T cells in rectal cancer (P < 0.05).It was positively correlated with M0 macrophages, activated mast cells, neutrophils, resting natural killer cells, activated CD4+ memory T cells and follicular helper T cells in gastric cancer (P < 0.05).⑤PHB was mainly enriched in class I receptors, PPAR and calcium signaling pathways (P < 0.05).⑥ The expression of PHB was positively correlated with the sensitivity of 13 drugs, including ammonafide, prasinolide and abiraterone (P < 0.05). Conclusion The expression of PHB is significantly related to the infiltration of various immune cells in DT and poor prognosis in DT patients, which may become a new biomarker and potential immunomodulatory target of DT.