Pan-cancer landscape of the RUNX protein family reveals their potential as carcinogenic biomarkers and the mechanisms underlying their action

[摘要] Background: The RUNX family of transcription factors plays an important regulatory rolein tumor development. Although the importance of RUNX in certain cancer types is wellknown, the pan-cancer landscape remains unclear. Materials and Methods: Data from TheCancer Genome Atlas (TCGA) provides a pan-cancer overview of the RUNX genes. Hence,herein, we performed a pan-cancer analysis of abnormal RUNX expression and decipheredthe potential regulatory mechanism. Specifically, we used TCGA multi-omics data combinedwith multiple online tools to analyze transcripts, genetic alterations, DNA methylation,clinical prognoses, miRNA networks, and potential target genes. Results: RUNX genes areconsistently overexpressed in esophageal, gastric, pancreatic, and pan-renal cancers. Thetotal protein expression of RUNX1 in lung adenocarcinoma, kidney renal clear cell carcinoma(KIRC), and uterine corpus endometrial carcinoma (UCEC) is consistent with the mRNAexpression results. Moreover, increased phosphorylation on the T14 and T18 residues ofRUNX1 may represent potential pathogenic factors. The RUNX genes are significantlyassociated with survival in pan-renal cancer, brain lower-grade glioma, and uveal melanoma.Meanwhile, various mutations and posttranscriptional changes, including the RUNX1 D96mutation in invasive breast carcinoma, the co-occurrence of RUNX gene mutations in UCEC,and methylation changes in the RUNX2 promoter in KIRC, may be associated with cancerdevelopment. Finally, analysis of epigenetic regulator co-expression, miRNA networks, andtarget genes revealed the carcinogenicity, abnormal expression, and direct regulation ofRUNX genes. Conclusions: We successfully analyzed the pan-cancer abnormal expressionand prognostic value of RUNX genes, thereby providing potential biomarkers for variouscancers. Further, mutations revealed via genetic alteration analysis may serve as a basis forpersonalized patient therapies.

[关键词] RUNX family;The Cancer Genome Atlas;pan-cancer analysis;prognosis;regulatory mechanism