Abstract
PurposeTo construct a novel radiogenomics biomarker based on hypoxic-gene subset for the accurate prognostic prediction of clear cell renal cell carcinoma (ccRCC).Materials and MethodsInitially, 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.ResultsThe 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).ConclusionsThe 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.
Highlights
Recognized as the most common urinary cancer, renal cell carcinoma was responsible for more than 175,000 deaths worldwide in 2020 [1, 2]
The current study focused on an important prognostic factor in Clear cell renal cell carcinoma (ccRCC): the association between hypoxia-related gene expression and the prognosis of patients with clear cell renal cell carcinoma
The risk model could be clearly separated from the PCA (Principal Component Analysis) analysis and the genomic signature established was independently correlated with the survival of ccRCC patients (Supplementary Materials II)
Summary
Recognized as the most common urinary cancer, renal cell carcinoma was responsible for more than 175,000 deaths worldwide in 2020 [1, 2]. Surgical resection remains the principal treatment for localized or locally advanced renal cell carcinoma. Surgically resected localized renal cancers have a 5-year survival ranging from 80% - 95%, non-metastatic renal cancers deemed to be high risk have a probability of recurrence or metastasis as high as 30% 40%, associated with an extremely high mortality rate [4]. With rather wide variability in the prognosis of individual patients with ccRCC, there is an urgent need for more precise and readily defined prognostic parameters to group patients according to disease risk, to facilitate individualized clinical oncology treatment options
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