Objectives Human cancer is considered to be an important cause of death worldwide. Polypyrimidine tract binding protein 1 (PTBP1) is emerging as a powerful pro-oncogenic factor in bladder and liver cancer; however, no pan-cancer analysis is presently available. Our study aimed to explore PTBP1 expression profiles, prognostic immunological value, and biological functions across various cancers. Methods We conducted a comprehensive analysis using multi-omics bioinformatics from public databases, including TIMER, GEPIA2, ProteinAtlas, Kaplan-Meier Plotter, PrognoScan, cBioPortal, STRING, ENCORI, TargetScan, and DAVID. Results We found that PTBP1 was overexpressed across multiple cancer types. qRT-PCR results demonstrated that the PTBP1 mRNA was significantly up-regulated in lung adenocarcinoma (LUAD), colon cancer (COAD), and melanoma (SKCM) cell lines, as well as in melanoma-forming mouse models. Higher PTBP1 mRNA levels were associated with poorer survival probabilities in several cancer types. PTBP1 genetic alterations were related to amplification and mutation. PTBP1 significantly modulates tumor immunity by enhancing Tregs infiltration and reducing CD8+ T cell activity, promoting immune evasion and adversely affecting cancer prognosis. GO and KEGG pathway analyses implied that PTBP1 may participate in RNA metabolism, the spliceosome, the cell cycle, and the p53 signaling pathway in cancer development. Conclusion Our study is the first to demonstrate the oncogenic role of PTBP1 in a pan-cancer context. PTBP1 might serve as a new biomarker for prognostic prediction and immune cell infiltration across cancers in the future.
