Related Experiment Video
Updated: Aug 25, 2025
Predictive Immune Modeling of Solid Tumors
Published on: February 25, 2020
PTPRD/PTPRT mutation as a predictive biomarker of immune checkpoint inhibitors across multiple cancer types
Xiaoling Shang1, Wengang Zhang2, Xun Zhang1
1Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, China.
Background:
Immune checkpoint inhibitors (ICIs) are dramatically changing the treatment landscape of a variety of cancers. Nevertheless, the variability in ICI responses highlight the importance in identifying predictive biomarkers. PTPRD and PTPRT (PTPRD/PTPRT) are the phosphatases of JAK-STAT signaling, a critical pathway in anti-cancer immunity regulation. However, the pan-cancer association between PTPRD/PTPRT mutation and the efficacy of ICIs remains unclear across pan-cancer patients.
Methods:
We analyzed the association between PTPRD/PTPRT mutations and patient outcomes using clinical data and genomic mutations from TCGA pan-cancer cohort. Furthermore, the ICI-treatment cohort was used to evaluate the relationship between PTPRD/PTPRT mutation and the efficacy of ICIs. Another ICIs-treatment cohort was used to validate the findings. The TCGA pan-cancer dataset was analyzed to explore the correlation between PTPRD/PTPRT mutations and immune signatures. Moreover, we combined four factors to construct a nomogram model that could be used to predict the survival of pan-cancer patients receiving ICI treatment. The calibration curves and area under the curve were applied to assess the performance of the model.
Results:
PTPRD/PTPRT mutations were shown to be associated with a worse prognosis in TCGA cohort (P < 0.05). In the Samstein cohort, prolonged overall survival (OS) was observed in PTPRD/PTPRT mutant cancers, compared with wild-type cancers (mOS: 40.00 vs 16.00 months, HR = 0.570, 95%CI: 0.479-0.679, P < 0.0001). In the validation cohort, significant OS advantage was observed in PTPRD/PTPRT mutant patients (mOS: 31.32 vs 15.53 months, HR = 0.658, 95%CI: 0.464-0.934, P = 0.0292). Furthermore, PTPRD/PTPRT mutations were associated with a higher tumor mutational burden, MSI score, and TCR score (P < 0.0001). Enhanced immune signatures were found in the PTPRD/PTPRT mutant cancers (P < 0.05). Finally, we successfully established a nomogram model that could be used to predict the survival of NSCLC patients who received ICI treatment. Based on the risk score of the model, patients in the low-risk group showed a better mOS than those in the high-risk group (mOS: 2.75 vs 1.08 years, HR = 0.567, 95%CI: 0.492-0.654; P < 0.001).
Conclusions:
PTPRD/PTPRT mutations may be a potential biomarker for predicting ICI treatment responsiveness in multiple cancer types.
Insights
Mutations in PTPRD and PTPRT genes are associated with improved outcomes for patients receiving immune checkpoint inhibitors (ICIs). These genetic alterations may serve as predictive biomarkers for ICI therapy across various cancers.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Immune checkpoint inhibitors (ICIs) are revolutionizing cancer treatment, but response variability necessitates predictive biomarkers.
- PTPRD and PTPRT phosphatases regulate JAK-STAT signaling, crucial for anti-cancer immunity.
- The role of PTPRD/PTPRT mutations in pan-cancer ICI efficacy is not well-defined.
Purpose of the Study:
- To investigate the association between PTPRD/PTPRT mutations and patient outcomes in a pan-cancer cohort.
- To evaluate the impact of PTPRD/PTPRT mutations on ICI treatment efficacy.
- To develop a predictive model for survival in patients receiving ICI therapy.
Main Methods:
- Analysis of TCGA pan-cancer cohort for PTPRD/PTPRT mutations and patient outcomes.
- Evaluation of ICI treatment cohorts to assess PTPRD/PTPRT mutation and ICI efficacy.
- Exploration of correlations between PTPRD/PTPRT mutations and immune signatures.
- Construction and validation of a nomogram for predicting survival in ICI-treated patients.
Main Results:
- PTPRD/PTPRT mutations were linked to improved overall survival (OS) in multiple cohorts (e.g., mOS 40.00 vs 16.00 months in Samstein cohort).
- Mutations correlated with higher tumor mutational burden, MSI, and TCR scores, indicating enhanced anti-tumor immunity.
- A nomogram model successfully predicted survival in NSCLC patients receiving ICI treatment, with low-risk groups showing better outcomes.
Conclusions:
- PTPRD/PTPRT mutations represent a potential predictive biomarker for ICI treatment response.
- These findings support the utility of PTPRD/PTPRT mutations in guiding cancer immunotherapy decisions.
- Further research can leverage these mutations for personalized immunotherapy strategies.
More Related Videos
07:47Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
Published on: September 15, 2023
09:32Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018