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Research Paper|Volume 11, Issue 17|pp 6999—7020

Prognostic value and immune infiltration of novel signatures in clear cell renal cell carcinoma microenvironment

Wen-Hao Xu1,2, Yue Xu3, Jun Wang1,2, Fang-Ning Wan1,2, Hong-Kai Wang1,2, Da-Long Cao1,2, Guo-Hai Shi1,2, Yuan-Yuan Qu1,2, Hai-Liang Zhang1,2, Ding-Wei Ye1,2
  • 1Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China
  • 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
  • 3Department of Ophthalmology, The First Affiliated Hospital of Soochow University, Suzhou 215000, P.R. China
* Equal contribution
Received: August 8, 2019Accepted: August 19, 2019Published: September 7, 2019
https://doi.org/10.18632/aging.102233

Copyright © 2019 Xu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Growing evidence has highlighted the immune response as an important feature of carcinogenesis and therapeutic efficacy in clear cell renal cell carcinoma (ccRCC). This study categorized ccRCC cases into high and low score groups based on their immune/stromal scores generated by the ESTIMATE algorithm, and identified an association between these scores and prognosis. Differentially expressed tumor environment (TME)-related genes extracted from common upregulated components in immune and stromal scores were described using functional annotations and protein–protein interaction (PPI) networks. Most PPIs were selected for further prognostic investigation. Many additional previously neglected signatures, including AGPAT9, AQP7, HMGCS2, KLF15, MLXIPL, PPARGC1A, exhibited significant prognostic potential. In addition, multivariate Cox analysis indicated that MIXIPL and PPARGC1A were the most significant prognostic signatures, and were closely related to immune infiltration in TCGA cohort. External prognostic validation of MIXIPL and PPARGC1A was undertaken in 380 ccRCC cases from a real-world cohort. These findings indicate the relevance of monitoring and manipulation of the microenvironment for ccRCC prognosis and precision immunotherapy.