Identification of prognostic biomarkers in papillary renal cell carcinoma and PTTG1 may serve as a biomarker for predicting immunotherapy response

Ann Med. 2022 Dec;54(1):211-226. doi: 10.1080/07853890.2021.2011956.

Abstract

Objective: This study aims to identify potential prognostic and therapeutic biomarkers in papillary renal cell carcinoma (pRCC).

Methods: Two microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were identified. The protein-protein interaction (PPI) networks and functional annotations of DEGs were established. Survival analysis was utilized to evaluate the prognostic significance of the DEGs and the association between the expression level of candidate biomarkers and various tumour-infiltrating immune cells was explored. The role of PTTG1 in tumour microenvironments (TME) was further explored using Single-cell RNA-seq and its prognostic and therapeutic significance was validated in Fudan University Shanghai Cancer Centre (FUSCC) cohort.

Results: Eight genes, including BUB1B, CCNB1, CCNB2, MAD2L1, TTK, CDC20, PTTG1, and MCM were found to be negatively associated with patients' prognosis. The expression level of PTTG1 was found to be significantly associated with lymphocytes, immunomodulators, and chemokine in the TCGA cohort. Single-cell RNA-seq information indicated that PTTG1 was strongly associated with the proliferation of T cells. In the FUSCC cohort, the expression level of PTTG1 was also statistically significant for both progression-free survival (PFS) and overall survival (OS) prediction (HR = 2.683, p < .001; HR = 2.673, p = .001). And higher expression level of PTTG1 was significantly associated with immune checkpoint blockade (ICB) response in the FUSCC cohort (χ2=3.99, p < .05).

Conclusions: Eight genes were identified as a prognostic biomarker and the expression level of PTTG1 was also found to serve as a potential predictor for ICB response in pRCC patients.Key messages:Eight genes, including BUB1B, CCNB1, CCNB2, MAD2L1, TTK, CDC20, PTTG1, and MCM were found to be negatively associated with pRCC patients' prognosis.Expression level of PTTG1 was significantly associated with tumour microenvironment including lymphocytes, immunomodulators, and chemokines.Higher expression level of PTTG1 was significantly associated with immune checkpoint blockade (ICB) response in FUSCC cohort.

Keywords: PTTG1; Papillary renal cell carcinoma; biomarker; immune checkpoint blockade; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Carcinoma, Renal Cell* / genetics
  • Carcinoma, Renal Cell* / therapy
  • China
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunologic Factors
  • Immunotherapy
  • Kidney Neoplasms* / genetics
  • Prognosis
  • Tumor Microenvironment / genetics

Substances

  • Biomarkers
  • Immunologic Factors

Grant support

This work is supported by Grants from the National Key Research and Development Program of China [No. 2019YFC1316005, National Natural Science Foundation of China [No. 81772706 and No. 81802525], and Shanghai Science and Technology Committee [No. 18511108000].