TY - JOUR
T1 - Omics-wide quantitative B-cell infiltration analyses identify GPR18 for human cancer prognosis with superiority over CD20
AU - Liu, Yuchen
AU - Wang, Li
AU - Lo, Kwok Wai
AU - Lui, Vivian Wai Yan
N1 - Funding Information:
also receives fundings from General Research Fund, Research Grant Council, Hong Kong government, Hong Kong SAR (#17121616, #1416857), Research Impact Fund (#R4017-18), the Health and Medical Research Fund (HMRF#15160691, the Health and Medical Research Fund, the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region), University-Industry Collaboration Program (UIM/329; Innovation and Technology Fund, Hong Kong government, Hong Kong SAR), and the Hong Kong Cancer Fund, Hong Kong SAR. Y.L. receives funding supports (Postdoctoral Hub PH-ITF Ref.: PiH/052/18 of UIM/329), from the Innovation and Technology Fund, Hong Kong government, Hong Kong SAR. K.-W.L. receives funding supports (Faculty Postdoctoral Fellowship Ref: FPFS/18-19/44 and FPFS/19-20/R/18) from the Chinese University of Hong Kong, Hong Kong SAR.
Funding Information:
This research is funded by the Lee Hysan Foundation Research Grant and Endowment Fund Research Grant Schemes 2018-2019 (CA11281, V.W.Y.L.) and 2019-2020 (CA11286, V.W.Y.L.), United College, the Chinese University of Hong Kong. V.W.Y.L.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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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U2 - 10.1038/s42003-020-0964-7
DO - 10.1038/s42003-020-0964-7
M3 - Article
C2 - 32398659
AN - SCOPUS:85084461925
SN - 2399-3642
VL - 3
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 234
ER -