Role of tumor necrosis factor alpha-induced protein 6 (TNFAIP6) in tumors: A pan-cancer analysis

Abstract

Abstract Background There is growing evidence that the gene named tumor necrosis factor α–induced protein 6 (TNFAIP6) has an important role in various tumors. However, a systematic pan-cancer analysis of TNFAIP6 is lacking. Here we aimed to analyze the expression of TNFAIP6 across multiple cancers and verify its expression during the progression of colon cancer. Methods We performed a comprehensive bioinformatics analysis to examine the expression of TNFAIP6 across 27 tumor types. GEPIA2 was used to evaluate the effect of TNFAIP6 on clinical cancer prognosis. cBioportal was used to assess TNFAIP6 mutations. The correlation between TNFAIP6 and cancer immune infiltrates was explored using TIMER2.0. The CancerSEA database was used to perform functional analysis of TNFAIP6. Metascape was used to identify TNFAIP6-related gene enrichment pathways. Immunohistochemistry was performed to detect TNFAIP6 protein expression in the colon cancer. In addition, the Comparative Toxicogenomics Database was searched for known and possible antitumor drugs that may be associated with TNFAIP6. Results We found that, in most of the cancers included in this analysis, TNFAIP6 was highly expressed, and there is a distinct relationship between TNFAIP6 expression and cancer prognosis. TNFAIP6 expression is associated with cancer-associated fibroblasts, neutrophils, and endothelial cells. TNFAIP6 and similar genes may also be involved in the PID_VEGF_VEGFR_ pathway. Immunohistochemistry revealed an increasing trend of TNFAIP6 protein expression in normal, adenoma, and colon cancer tissues. Several known and possible antitumor drugs that may be associated with TNFAIP6 were identified in the Comparative Toxicogenomics Database. These results suggest that a number of drugs may target TNFAIP6 during cancer treatment, including cisplatin, irinotecan, resveratrol, U 0126, NSC689534, genistein, NSC668394, oxaliplatin, plerixafor, topotecan, vincristine, flutamide, doxorubicin, MRK 003, folic acid, demecolcine, tunicamycin, zoledronic acid, and schizandrin B. Conclusions TNFAIP6 may function as an oncogene in certain cancers. Furthermore, this study provides evidence that TNFAIP6 is an important factor in colon cancer progression.