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Research Paper|Volume 16, Issue 3|pp 2090—2122

MAEL in human cancers and implications in prognostication and predicting benefit from immunotherapy over VEGFR/mTOR inhibitors in clear cell renal cell carcinoma: a bioinformatic analysis

Jin Tao1, Jinshan Cui1, Yu Xu2, Yafeng Fan1, Guodong Hong1, Qiaoxia Zhou2, Guoqiang Wang2, Leo Li2, Yusheng Han2, Chunwei Xu3, Wenxian Wang4, Shangli Cai2, Xuepei Zhang1
  • 1Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
  • 2Burning Rock Biotech, Guangzhou, Guangdong, China
  • 3Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
  • 4Department of Clinical Trial, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China
* Equal contribution
Received: August 15, 2023Accepted: December 13, 2023Published: January 31, 2024
https://doi.org/10.18632/aging.205470

Copyright: © 2024 Tao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Maelstrom (MAEL), a novel cancer/testis-associated gene, may facilitate the initiation and progression of human malignancies, warranting comprehensive investigations. Single-cell and tissue-bulk transcriptomic data demonstrated higher MAEL expression in testis (spermatogonia/spermatocyte), kidney (proximal tubular cell), and brain (neuron/astrocyte), and corresponding cancers, including testicular germ cell tumor, glioma, papillary renal cell carcinoma, and clear cell renal cell carcinoma (ccRCC). Of these cancers, only in ccRCC did MAEL expression exhibit associations with both recurrence-free survival and overall survival. High MAEL expression was associated with an anti-inflammatory tumor immune microenvironment and VEGFR/mTOR activation in ccRCC tissues and high sensitivities to VEGFR/PI3K-AKT-mTOR inhibitors in ccRCC cell lines. Consistent with these, low rather than high MAEL expression indicated remarkable progression-free survival benefits from immune checkpoint inhibitor (ICI)-based immunotherapies over VEGFR/mTOR inhibitors in two large phase III trials (JAVELIN Renal 101 and CheckMate-025). MAEL is a biologically and clinically significant determinant with potential for prognostication after nephrectomy and patient selection for VEGFR/mTOR inhibitors and immunotherapy-based treatments.