Journal
COMMUNICATIONS BIOLOGY
Volume 3, Issue 1, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s42003-020-0964-7
Keywords
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Funding
- Lee Hysan Foundation
- General Research Fund, Research Grant Council, Hong Kong government, Hong Kong SAR [17121616, 1416857]
- Research Impact Fund [R401718]
- Health and Medical Research Fund (HMRF) [15160691]
- Health and Medical Research Fund (Food and Health Bureau)
- Health and Medical Research Fund (Government of the Hong Kong Special Administrative Region)
- University-Industry Collaboration Program [UIM/329]
- Hong Kong Cancer Fund, Hong Kong SAR
- Innovation and Technology Fund, Hong Kong government, Hong Kong SAR [PiH/052/18]
- Chinese University of Hong Kong, Hong Kong SAR [FPFS/18-19/44, FPFS/19-20/R/18]
- Endowment Fund Research Grant Scheme 2018-2019, United College, the Chinese University of Hong Kong [CA11281]
- Endowment Fund Research Grant Scheme 2019-2020, United College, the Chinese University of Hong Kong [CA11286]
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Tumor-infiltrating B lymphocyte (TIL-B), and TIL-B-related biomarkers have clinical prognostic values for human cancers. CD20 (encoded by MS4A1) is a widely used TIL-B biomarker. Using TCGA-quantitative multiomics datasets, we first cross-compare prognostic powers of intratumoral CD20 protein, mRNA and TIL-B levels in pan-cancers. Here, we show that MS4A1 and TIL-B are consistently prognostic in 5 cancers (head and neck, lung, cervical, kidney and low-grade glioma), while unexpectedly, CD20 protein levels lack quantitative correlations with MS4A1/TIL-B levels and demonstrate limited prognosticity. Subsequent bioinformatics discovery for TIL-B prognostic gene identifies a single gene, GPR18 with stand-alone prognosticity across 9 cancers (superior over CD20), with further validations in multiple non-TCGA cohorts. GPR18's immune signature denotes major B-cell-T-cell interactions, with its intratumoral expression strongly tied to a T-cell active, likely cytolytic, status across human cancers, suggesting its functional link to cytolytic T-cell activity in cancer. GPR18 merits biological and clinical utility assessments over CD20.
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