PTPRO-related CD8+ T-cell signatures predict prognosis and immunotherapy response in patients with breast cancer

Hongmei Dong; Chaoyu Xie; Zhimeng Yao; Ruijun Zhao; Yusheng Lin; Yichen Luo; Shuanglong Chen; Yanfang Qin; Yexi Chen; Hao Zhang

doi:10.3389/fimmu.2022.947841

PTPRO-related CD8⁺ T-cell signatures predict prognosis and immunotherapy response in patients with breast cancer

Front Immunol. 2022 Aug 8:13:947841. doi: 10.3389/fimmu.2022.947841. eCollection 2022.

Authors

Hongmei Dong¹, Chaoyu Xie¹, Zhimeng Yao^{1

2}, Ruijun Zhao³, Yusheng Lin^{1

4

5}, Yichen Luo¹, Shuanglong Chen¹, Yanfang Qin⁶, Yexi Chen⁷, Hao Zhang^{2

7

8}

Affiliations

¹ Institute of Precision Cancer Medicine and Pathology, School of Medicine, Jinan University, Guangzhou, China.
² Department of General Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China.
³ Department of Breast Surgery, The Third Hospital of Nanchang, Nanchang, China.
⁴ Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
⁵ Graduate School, Shantou University Medical College, Shantou, China.
⁶ Department of Pathology, School of Medicine, Jinan University, Guangzhou, China.
⁷ Department of General Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China.
⁸ Institute of Precision Cancer Medicine and Pathology, School of Medicine, and Minister of Education Key Laboratory of Tumor Molecular Biology, Jinan University, Guangzhou, China.

Abstract

Background: Poor immunogenicity and extensive immunosuppressive T-cell infiltration in the tumor immune microenvironment (TIME) have been identified as potential barriers to immunotherapy success in "immune-cold" breast cancers. Thus, it is crucial to identify biomarkers that can predict immunotherapy efficacy. Protein tyrosine phosphatase receptor type O (PTPRO) regulates multiple kinases and pathways and has been implied to play a regulatory role in immune cell infiltration in various cancers.

Methods: ESTIMATE and single-sample gene set enrichment analysis (ssGSEA) were performed to uncover the TIME landscape. The correlation analysis of PTPRO and immune infiltration was performed to characterize the immune features of PTPRO. Univariate and multivariate Cox analyses were applied to determine the prognostic value of various variables and construct the PTPRO-related CD8⁺ T-cell signatures (PTSs). The Kaplan-Meier curve and the receiver operating characteristic (ROC) curve were used to estimate the performance of PTS in assessing prognosis and immunotherapy response in multiple validation datasets.

Results: High PTPRO expression was related to high infiltration levels of CD8⁺ T cells, as well as macrophages, activated dendritic cells (aDCs), tumor-infiltrating lymphocytes (TILs), and Th1 cells. Given the critical role of CD8⁺ T cells in the TIME, we focused on the impact of PTPRO expression on CD8⁺ T-cell infiltration. The prognostic PTS was then constructed using the TCGA training dataset. Further analysis showed that the PTS exhibited favorable prognostic performance in multiple validation datasets. Of note, the PTS could accurately predict the response to immune checkpoint inhibitors (ICIs).

Conclusion: PTPRO significantly impacts CD8⁺ T-cell infiltration in breast cancer, suggesting a potential role of immunomodulation. PTPRO-based PTS provides a new immune cell paradigm for prognosis, which is valuable for immunotherapy decisions in cancer patients.

Keywords: PTPRO; PTPRO-related CD8+ T-cell marker genes signature; TILs; breast cancer; immune cell; immunotherapy response indicator; prognosis.

MeSH terms

Breast Neoplasms* / metabolism
Breast Neoplasms* / therapy
CD8-Positive T-Lymphocytes
Female
Humans
Immunotherapy
Phosphoric Monoester Hydrolases
Prognosis
Receptor-Like Protein Tyrosine Phosphatases, Class 3* / genetics
Tumor Microenvironment

Substances

Phosphoric Monoester Hydrolases
PTPRO protein, human
Receptor-Like Protein Tyrosine Phosphatases, Class 3