Next‐generation sequencing identifies that protein tyrosine phosphatase receptor type D mutation is favorable to immunotherapy in human cancer

Author:

Huang Yongsheng1ORCID,Liao Jianwei1,Gao Ming2,Fu Sha1,Liang Faya3,Jiang Yuanling1,Luo Jiahuan1,Huang Jinghua1,Tan Ni1,Wang Danlan1,Yin Xinke1,Ren Shuwei4,Lin Peiliang3,Chen Renhui3,Han Ping3,Huang Xiaoming3,Ouyang Nengtai1

Affiliation:

1. Cellular & Molecular Diagnostics Center, Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou China

2. Department of Radiology, Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou China

3. Department of Otolaryngology–Head and Neck Surgery, Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou China

4. Department of Clinical Laboratory, The Sixth Affiliated Hospital Sun Yat‐sen University Guangzhou Guangdong China

Abstract

AbstractProtein tyrosine phosphatase receptors (PTPRs) play a crucial part in numerous tumor processes. However, the effect of PTPR mutations on the immune checkpoint inhibitor (ICI) response needs to be further clarified. Next‐generation sequencing was performed on 453 cancer patients in our internal cohort. The genomic alterations, tumor mutation burden (TMB), neoantigens, and immune‐related features/pathways of other cohorts were analyzed. Here, protein tyrosine phosphatase receptor type D (PTPRD) has a high mutation frequency and an intensified co‐occurrence with other PTPRs. Patients who responded to ICI therapy were enriched with the PTPRD mutation (PTPRD‐MUT). PTPRD‐MUT patients had a higher objective response rate (44.1% vs. 29.1%), TMB/neoantigens, and longer overall survival time than PTPRD‐wild‐type (PTPRD‐WT) patients. Genomic alterations with a higher mutation frequency of genes (such as LRP1B) were enriched in PTPRD‐MUT patients. More abundant immune cells (including CD8+ T cells and macrophages) and upregulated immune‐related genes were found in PTPRD‐MUT patients. Moreover, Gene sets enrichment analyses showed that multiple antitumor immune pathways are activated in PTPRD‐MUT patients. Therefore, PTPRD‐MUT is beneficial for immunotherapy of multiple cancer types and may be a predictive biomarker of patient clinical outcomes.

Funder

National Natural Science Foundation of China

Publisher

Wiley

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