Construction of a Novel Multigene Panel Potently Predicting Poor Prognosis in Patients with Clear Cell Renal Cell Carcinoma

Cancers

Xiaozeng Lin¹  MathildaJing Chow¹  Jingyi Peng¹  Damu Tang¹  Yan Gu¹  Pierre Major²  Anil Kapoor³ 

[1] Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada;Department of Oncology, McMaster University, Hamilton, ON L8S 4L8, Canada;Urological Cancer Center for Research and Innovation (UCCRI), St Joseph’s Hospital, Hamilton, ON L8N 4A6, Canada;

关键词: clear cell renal cell carcinoma;    IQGAP1;    overall survival;    disease-specific survival;    progression-free survival;    metastasis;   

DOI  :  10.3390/cancers12113471

来源: DOAJ

【 摘 要 】

We observed associations of IQGAP1 downregulation with poor overall survival (OS) in clear cell renal cell carcinoma (ccRCC). Differentially expressed genes (DEGs, n = 611) were derived from ccRCCs with (n = 111) and without IQGAP1 (n = 397) reduction using the TCGA PanCancer Atlas ccRCC dataset. These DEGs exhibit downregulations of immune response and upregulations of DNA damage repair pathways. Through randomization of the TCGA dataset into a training and testing subpopulation, a 9-gene panel (SigIQGAP1NW) was derived; it predicts poor OS in training, testing, and the full population at a hazard ratio (HR) 2.718, p < 2 × 10⁻¹⁶, p = 1.08 × 10⁻⁵, and p < 2 × 10⁻¹⁶, respectively. SigIQGAP1NW independently associates with poor OS (HR 1.80, p = 2.85 × 10⁻⁶) after adjusting for a set of clinical features, and it discriminates ccRCC mortality at time-dependent AUC values of 70% at 13.8 months, 69%/31M, 69%/49M, and 75.3%/71M. All nine component genes of SigIQGAP1NW are novel to ccRCC. The inclusion of RECQL4 (a DNA helicase) in SigIQGAP1NW agrees with IQGAP1 DEGs enhancing DNA repair. THSD7A affects kidney function; its presence in SigIQGAP1NW is consistent with our observed THSD7A downregulation in ccRCC (n = 523) compared to non-tumor kidney tissues (n = 100). Collectively, we report a novel multigene panel that robustly predicts poor OS in ccRCC.

【 授权许可】

Unknown