Cuproptosis in ccRCC: key player in therapeutic and prognostic targets

Yang Lv; Qiang Li; Lu Yin; Shaohua He; Chao Qin; Zhongwen Lu; Hongqi Chen

doi:10.3389/fonc.2023.1271864

Cuproptosis in ccRCC: key player in therapeutic and prognostic targets

Front Oncol. 2023 Oct 27:13:1271864. doi: 10.3389/fonc.2023.1271864. eCollection 2023.

Authors

Yang Lv¹, Qiang Li¹, Lu Yin², Shaohua He¹, Chao Qin¹, Zhongwen Lu³, Hongqi Chen¹

Affiliations

¹ Department of Urology, The Affiliated Jiangsu Shengze Hospital of Nanjing Medical University, Suzhou, China.
² Department of Traditional Chinese Medicine, Hong Kong Baptist University, Hong Kong, Hong Kong SAR, China.
³ Department of Urology, The Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Abstract

Background: Classical biomarkers have been used to classify clear cell renal cell carcinoma (ccRCC) patients in a variety of ways, and emerging evidences have indicated that cuproptosis is closely related to mitochondrial metabolism, thereby accelerating the development and progression of ccRCC. Nevertheless, the specific relationship between cuproptosis and the prognosis and treatment of ccRCC remains unclear.

Methods: We comprehensively integrated several ccRCC patient datasets into a large cohort. Following that, we systematically analyzed multi-omics data to demonstrate the differences between two cuproptosis clusters.

Results: We identified two cuproptosis clusters in ccRCC patients. Among the two clusters, cluster 1 patients showed favorable prognosis. We then confirmed the significant differences between the two clusters, including more typical cancer hallmarks were enriched in cluster 2 patients; cluster 2 patients were more susceptible to develop mutations and had a lower level of gistic score and mRNAsi. Importantly, both Tumor Immune Dysfunction and Exclusion analysis and subclass mapping algorithm showed that cuproptosis 1 patients were more susceptible to be responded to immunotherapy. In addition, a prognostic signature was successfully developed and also showed prominent predictive power in response to immunotherapy.

Conclusion: As a result of our findings, we were able to classify ccRCC patients according to cuproptosis in a novel way. By constructing the cuproptosis clusters and developing the signature, patients with ccRCC could have a more accurate prognosis prediction and better immunotherapy options.

Keywords: clear cell renal cell carcinoma; cuproptosis; immunotherapy; prognosis; tumor immune microenvironment.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The Mechanism and Clinical Application of Nrf3 Methylated m6A Modification in Environmental Endocrine Disruptor-Induced Male Erectile Dysfunction (Suzhou Science and Technology Plan Project No.: SKJYD2021030). CircRNALPAR3’s Clinical Diagnosis and Treatment Judgment and Related Mechanisms of Prostate Cancer (Suzhou Science and Technology Plan Project No.: SKY2022032). LncRNA-AC124854.1 participates in the reactivation of PI3K/AKTmTOR pathway by regulating the expression of microtubule-associated protein 4 and promotes the clinical application of drug resistance in kidney cancer BEZ235 (Project No.: wwk202104). “Effects of the Chinese medicine Cat's Whiskers on Chronic Renal Failure” (Project number of "Promoting Health through Science and Education" in Wujiang District, Suzhou City: wwk201717). Research on the Application of Transrectal Ultrasound Targeted Injection of Silk Fibroin/Iron Oxide Composite Hydrogel Magnetic Heat in the Treatment of Prostate Cancer" (Suzhou Science and Technology Plan Project Number: SKYD2023023).