A Novel Radiogenomics Biomarker Based on Hypoxic-Gene Subset: Accurate Survival and Prognostic Prediction of Renal Clear Cell Carcinoma

Purpose To construct a novel radiogenomics biomarker based on hypoxic-gene subset for the accurate prognostic prediction of clear cell renal cell carcinoma (ccRCC).

Materials and Methods Initially, we screened for the desired hypoxic-gene subset by analysis using the GSEA database. Through univariate and multivariate cox regression hazard ratio analysis, survival-related hypoxia genes were identified, and a genomics signature was constructed in the TCGA database. Building on this, a hypoxia-gene related radiogenomics biomarker (prediction of hypoxia-genes signature by contrast-enhanced CT radiomics) was constructed in the TCIA-KIRC database by extracting features in the venous phase of contrast-enhanced CT images, selecting features using the mRMR and LASSO algorithms, and building logistic regression models. Finally, we validated the prognostic capability of the new biomarker for patients with ccRCC in an independent validation cohort at Huashan Hospital of Fudan University, Shanghai, China.

Results The hypoxia-related genomics signature consisting of five genes (IFT57, PABPN1, RNF10, RNF19B and UBE2T) was shown to be significantly associated with survival for patients with ccRCC in the TCGA database, delineated by grouping of the signature expression as either low- or high-risk. In the TCIA database, we constructed a radiogenomics biomarker consisting of 13 radiomics features that were optimal predictors of hypoxia-gene signature expression levels (low- or high-risk) in patients at each institution, that demonstrated AUC values of 0.91 and 0.91 in the training and validation groups, respectively. In the independent validation cohort at Huashan Hospital, our radiogenomics biomarker was significantly associated with prognosis in patients with ccRCC (p=0.0059).

Conclusions The novel prognostic radiogenomics biomarker that was constructed achieved excellent correlation with prognosis in both the cohort of TCGA/TCIA-KIRC database and the independent validation cohort of Huashan hospital patients with ccRCC. It is anticipated that this work may assist in clinical preferential treatment decisions and promote the process of precision theranostics in the future.