Prognostic Relevance of ZNF844 and Chr 19p13.2 KRAB-Zinc Finger Proteins in Clear Cell Renal Carcinoma

• Published in: Cancer genomics & proteomics Vol. 19; no. 3; pp. 305 - 327
• Main Authors: Heyliger, Simone O, Soliman, Karam F A, Saulsbury, Marilyn D, Reams, R Renee
• Format: Journal Article
• Language: English
• Published: Greece International Institute of Anticancer Research 01.05.2022
• Subjects: Animals; Bioinformatics; Biomarkers; Biomarkers, Tumor - genetics; Cancer; Carcinogenesis; Carcinogens; Carcinoma, Renal Cell - pathology; CD4 antigen; Chromosome 19; Clear cell-type renal cell carcinoma; Female; Gene set enrichment analysis; Genomes; Humans; Kidney cancer; Kidney Neoplasms - pathology; Lymphocytes T; Male; Mammals - metabolism; Medical prognosis; Metastases; Phenotypes; Prognosis; Proteins; Repressor Proteins - genetics; Transcription Factors - genetics; Transcription Factors - metabolism; Tumor suppressor genes; Tumors; Zinc; Zinc finger proteins; Zinc Fingers - physiology; KRAB-ZFPs; Chr19p13.2; Th1 cells; ccRCC; ZNF844; Kruppel-associated box; tumor microenvironment; biomarker; ZNF433; clear cell renal carcinoma
• ISSN: 1109-6535; 1790-6245
• DOI: 10.21873/cgp.20322

Clear-cell renal cell carcinoma (ccRCC) is the most common and aggressive form of all urological cancers, with poor prognosis and high mortality. Despite growing evidence of involvement in carcinogenesis, the role of KRAB-ZFP in ccRCC has not been fully explored. KRAB Zinc finger proteins (KRAB-ZFPs) are the largest family of mammalian transcription regulators. They are differentially expressed in various tissues during cellular development and phenotypic differentiation. In this study, the levels of transcripts of ccRCC from The Cancer Genome Atlas (TCGA) dataset were used to identify prognostic biomarkers in this disease. Using bioinformatics techniques, we demonstrate that approximately 60% of KRAB zinc finger proteins located on chromosome 19p13.2 are differentially expressed, with all but two being down-regulated in ccRCC. Moreover, ZNF844, a paralog of ZNF433, was the most down-regulated across all histological grades and pathological stages (p<0.001). In addition, the decrease in ZNF844 expression was associated with poor patient survival (HR=0.41; 95% CI=0.3-0.56; p<0.0001). Gene Set Enrichment Analysis of genes inversely co-expressed with ZNF844 revealed that enriched pathways were consistently related to immune and translation processes (p<0.05, FDR <0.05). Lastly, ZNF844 expression showed moderate, inverse correlation to Helper T-cell (CD4 or Th1) subtype 1 (R=-0.558, p=5.15×10 ) infiltration and with the exhausted T-cell phenotype (R=-0.37; p=4.1×10 ). Down-regulation of KRAB-ZFPs at 19p13.2 may represent a signature for ccRCC. Moreover, ZNF844 is a prognostic marker for ccRCC and may serve as a putative immune-related tumor suppressor gene.