Serum Protein Markers May Aid in RCC Detection and Prognosis

Elevated levels of certain proteins may serve as potential biomarkers for renal cell carcinoma (RCC) diagnosis and prognosis, according to findings presented during the SUO 25^th Annual Meeting.

“While tools like circulating tumor DNA and other forms of liquid biopsy have proven useful in managing urothelial cancer, similar diagnostic and prognostic tools for RCC remain to be elucidated,” said Laura Elizabeth Davis and colleagues.

To identify protein-cancer associations with RCC development and progression, the team evaluated three cohorts, including patients who had received a diagnosis of RCC (n=2245), patients who were disease-free at serum collection but later developed RCC (n=1225), and people without cancer (control cohort n=44,386).

The researchers used UK Biobank to obtain patient information, then Olink, a technology that helps provide protein biomarker screening, to analyze serum proteomic data for over 2,900 proteins.

All groups were adjusted for age, gender, body mass index, and smoking status. Cox proportional hazards regression models were used to estimate hazard ratios (HRs), 95% confidence intervals (CI), and sensitivity and specificity analyses. Generated area under the curve (AUC) values helped to evaluate diagnostic performance of the identified biomarkers.

The study showed five proteins that were most expressed in each cohort: TAFA5, KLK11, KLK8, CDSN, and CLMP. Furthermore, TAFA5 showed the highest HR (9.7) in the treated cohort (95% CI 6.3-12.01, P < .001).

In addition, a receiver operating characteristic curve analysis displayed significant diagnostic performance for IGFBP4, TAFA5, TGFBR2, SCARB2, and NECTIN4.

Upon examining AUC values, the researchers discovered strong predictive capabilities for IGFBP4, TAFA5, TGFBR2, SCARB2, and NECTIN4. With IGFBP4, the AUC was .9127, a sensitivity of .8056, and a specificity of .8606. Values for the other proteins were as follows: TAFA5 (AUC .9134, sensitivity .7500, and specificity .8996), TGFBR2 (AUC .9057, sensitivity .6667, and specificity .9083), SCARB2 (AUC .8968, sensitivity .7500, and specificity .9197), and NECTIN4 (AUC .9269, sensitivity .7222, and specificity .9299).

“These findings indicate that specific proteomic biomarkers may have a significant association with RCC diagnosis, with high AUC values supporting their potential utility in RCC diagnosis and prognosis,” the researchers said.

To help investigate reliable biomarkers for RCC, the researchers said prospective validation is needed.

Reference

Davis LE, Wang B, Maina E, et al. Innovative diagnostic approaches: serum protein markers in renal cell carcinoma. Poster #137. Presented at the 25th Annual Meeting of the Society of Urologic Oncology; December 4-6, 2024; Dallas, Texas.