Association of immune checkpoint inhibitor with survival in patients with cancers with protein tyrosine phosphatase receptor T mutation

Abstract

Dear Editor, We and others have shown that the tumor mutation burden (TMB) and several underlying oncogenic alterations could provide clinically predictive implications for immune checkpoint inhibitor (ICI). 1-3 Protein tyrosine phosphatases (PTPs) consist of a variety classes, and most of them are highly mutated in multiple cancers and are closely interact with innate and acquired immunity regulating immune cell activation and differentiation. 4,5 PTP receptor T (PTPRT) has been found to be the most frequently mutated PTP gene in cancers and could predict poor prognosis; 4,6 however, the association of PTPRT mutation with clinical outcomes of ICI remains unknown. Here, we performed a comprehensive pancancer investigation to clinically validate PTPRT mutation as a predictive biomarker for ICI therapy. We collected clinical and PTPRT mutational data quantified by whole exome sequencing of 2129 cancer patients treated with ICI and 10,814 cancer patients without receiving ICI from the cBioPortal, PubMed, and The Cancer Genome Atlas. The study protocol was approved by the ethics committee of the Sun Yat-sen Memorial Hospital of Sun Yat-sen University. The requirement for informed consent of study participants and the permission to use the patient data were waived because the human data were obtained from publicly available datasets. All analyses were performed according to the STROBE guideline from September 18 through October 1, 2019. Overall survival (OS) were primary outcomes, which were computed using the Kaplan-Meier method and were assessed with the log-rank test and the hazard ratio (HR) calculated by the Cox regression model. The TMB in PTPRT wildtype versus mutant groups were compared with Wilcoxon rank-sum tests. All analyses were performed using R (version 3.4.4) and were considered statistically significant if P values < .05. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Anchored Multiplex PCR Custom Melanoma Next Generation Sequencing Panel for Analysis of Circulating Tumor DNA

“…Of note, PTPRT E324K, along with MAP2K1 P124L, was detected in treatment naïve sample 16 which also harbored a BRAF V600K mutation ( Figure 2 ). In melanoma, mutations in PTPRT, such as E324K, which create neoepitopes, may be associated with better outcomes for patients on immunotherapy ( 75 ). This may have been an option for this patient who subsequently had a partial response to combination BRAF/MEK inhibition with the presence of MAP2K1 P124L presumably contributing to resistance ( 76 , 77 ).…”

Association of PTPRT mutations with immune checkpoint inhibitors response and outcome in melanoma and non‐small cell lung cancer

“…Recent two studies also revealed PTPRT mutations may be implicated in immunotherapy response. 65 , 66 He et al 65 used only one aggregated tumor cohort to explore the potential connection of PTPRT mutations and did not conduct the multivariate‐adjusted analyses, these may introduce biases to the final results. Wang et al 66 performed the relevant exploration only for NSCLC patients and lacked additional cancer type validation.…”

Association of PTPRT Mutations with Cancer Metastasis in Multiple Cancer Types

“…The gene may be involved in both signal transduction and cellular adhesion and is also known to inhibit malignant cell proliferation by inhibiting the STAT3 pathway [4][5][6][7]. Recent studies have reported that PTPRT mutations may be associated with the tumor mutation burden (TMB) and could provide clinically predictive implications for immune checkpoint inhibitor (ICI) therapies [8,9]. Hu et al reported that PTPRT may be involved in the early metastatic seeding of colorectal cancer [10].…”

“…To address this question, we retrospectively analyzed the somatic mutations and cancer prognostic status from the previously published data [7][8][9]. The integration of somatic mutations and clinical prognostic information from multiple cohorts retrieved 16,182 metastatic and/or stage IV cancers and 26,480 early primary cancers.…”