A novel model for predicting immunotherapy response and prognosis in NSCLC patients

Abstract Background How to screen beneficiary populations has always been a clinical challenge in the treatment of non-small-cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs). Routine blood tests, due to their advantages of being minimally invasive, convenient, and capable of reflect...

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Main Authors: Ting Zang, Xiaorong Luo, Yangyu Mo, Jietao Lin, Weiguo Lu, Zhiling Li, Yingchun Zhou, Shulin Chen
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Cancer Cell International
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Online Access:https://doi.org/10.1186/s12935-025-03800-3
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author Ting Zang
Xiaorong Luo
Yangyu Mo
Jietao Lin
Weiguo Lu
Zhiling Li
Yingchun Zhou
Shulin Chen
author_facet Ting Zang
Xiaorong Luo
Yangyu Mo
Jietao Lin
Weiguo Lu
Zhiling Li
Yingchun Zhou
Shulin Chen
author_sort Ting Zang
collection DOAJ
description Abstract Background How to screen beneficiary populations has always been a clinical challenge in the treatment of non-small-cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs). Routine blood tests, due to their advantages of being minimally invasive, convenient, and capable of reflecting tumor dynamic changes, have potential value in predicting the efficacy of ICIs treatment. However, there are few models based on routine blood tests to predict the efficacy and prognosis of immunotherapy. Methods Patients were randomly divided into training cohort and validation cohort at a ratio of 2:1. The random forest algorithm was applied to select important variables based on routine blood tests, and a random forest (RF) model was constructed to predict the efficacy and prognosis of ICIs treatment. For efficacy prediction, we assessed receiver operating characteristic (ROC) curves, decision curve analysis (DCA) curves, clinical impact curve (CIC), integrated discrimination improvement (IDI) and net reclassification improvement (NRI) compared with the Nomogram model. For prognostic evaluation, we utilized the C-index and time-dependent C-index compared with the Nomogram model, Lung Immune Prognostic Index (LIPI) and Systemic Inflammatory Score (SIS). Patients were classified into high-risk and low-risk groups based on RF model, then the Kaplan–Meier (K–M) curve was used to analyze the differences in progression-free survival (PFS) and overall survival (OS) of patients between the two groups. Results The RF model incorporated RDW-SD, MCV, PDW, CD3+CD8+, APTT, P-LCR, Ca, MPV, CD4+/CD8+ ratio, and AST. In the training and validation cohorts, the RF model exhibited an AUC of 1.000 and 0.864, and sensitivity/specificity of (100.0%, 100.0%) and (70.3%, 93.5%), respectively, which had superior performance compared to the Nomogram model (training cohort: AUC = 0.531, validation cohort: AUC = 0.552). The C-index of the RF model was 0.803 in the training cohort and 0.712 in the validation cohort, which was significantly higher than Nomogram model, LIPI and SIS. K-M survival curves revealed that patients in the high-risk group had significantly shorter PFS/OS than those in the low-risk group. Conclusions In this study, we developed a novel model (RF model) to predict the response to immunotherapy and prognosis in NSCLC patients. The RF model demonstrated better predictive performance for immunotherapy responses than the Nomogram model. Moreover, when predicting the prognosis of immunotherapy, it outperformed the Nomogram model, LIPI, and SIS.
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spelling doaj-art-f565956e670d41b4bcf858daa0a4ae3f2025-08-20T03:10:32ZengBMCCancer Cell International1475-28672025-05-0125111310.1186/s12935-025-03800-3A novel model for predicting immunotherapy response and prognosis in NSCLC patientsTing Zang0Xiaorong Luo1Yangyu Mo2Jietao Lin3Weiguo Lu4Zhiling Li5Yingchun Zhou6Shulin Chen7The First Clinical Medical College and the First Affiliated Hospital of Guangzhou University of Chinese MedicineThe First Clinical Medical College and the First Affiliated Hospital of Guangzhou University of Chinese MedicineThe First Clinical Medical College and the First Affiliated Hospital of Guangzhou University of Chinese MedicineThe First Affiliated Hospital of Guangzhou University of Chinese MedicineThe First Affiliated Hospital of Guangzhou University of Chinese MedicineDepartment of Clinical Laboratory, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer CenterThe First Affiliated Hospital of Guangzhou University of Chinese MedicineDepartment of Clinical Laboratory, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer CenterAbstract Background How to screen beneficiary populations has always been a clinical challenge in the treatment of non-small-cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs). Routine blood tests, due to their advantages of being minimally invasive, convenient, and capable of reflecting tumor dynamic changes, have potential value in predicting the efficacy of ICIs treatment. However, there are few models based on routine blood tests to predict the efficacy and prognosis of immunotherapy. Methods Patients were randomly divided into training cohort and validation cohort at a ratio of 2:1. The random forest algorithm was applied to select important variables based on routine blood tests, and a random forest (RF) model was constructed to predict the efficacy and prognosis of ICIs treatment. For efficacy prediction, we assessed receiver operating characteristic (ROC) curves, decision curve analysis (DCA) curves, clinical impact curve (CIC), integrated discrimination improvement (IDI) and net reclassification improvement (NRI) compared with the Nomogram model. For prognostic evaluation, we utilized the C-index and time-dependent C-index compared with the Nomogram model, Lung Immune Prognostic Index (LIPI) and Systemic Inflammatory Score (SIS). Patients were classified into high-risk and low-risk groups based on RF model, then the Kaplan–Meier (K–M) curve was used to analyze the differences in progression-free survival (PFS) and overall survival (OS) of patients between the two groups. Results The RF model incorporated RDW-SD, MCV, PDW, CD3+CD8+, APTT, P-LCR, Ca, MPV, CD4+/CD8+ ratio, and AST. In the training and validation cohorts, the RF model exhibited an AUC of 1.000 and 0.864, and sensitivity/specificity of (100.0%, 100.0%) and (70.3%, 93.5%), respectively, which had superior performance compared to the Nomogram model (training cohort: AUC = 0.531, validation cohort: AUC = 0.552). The C-index of the RF model was 0.803 in the training cohort and 0.712 in the validation cohort, which was significantly higher than Nomogram model, LIPI and SIS. K-M survival curves revealed that patients in the high-risk group had significantly shorter PFS/OS than those in the low-risk group. Conclusions In this study, we developed a novel model (RF model) to predict the response to immunotherapy and prognosis in NSCLC patients. The RF model demonstrated better predictive performance for immunotherapy responses than the Nomogram model. Moreover, when predicting the prognosis of immunotherapy, it outperformed the Nomogram model, LIPI, and SIS.https://doi.org/10.1186/s12935-025-03800-3Non-small cell lung cancerPredictive biomarkersImmune checkpoint inhibitorsMachine learning
spellingShingle Ting Zang
Xiaorong Luo
Yangyu Mo
Jietao Lin
Weiguo Lu
Zhiling Li
Yingchun Zhou
Shulin Chen
A novel model for predicting immunotherapy response and prognosis in NSCLC patients
Cancer Cell International
Non-small cell lung cancer
Predictive biomarkers
Immune checkpoint inhibitors
Machine learning
title A novel model for predicting immunotherapy response and prognosis in NSCLC patients
title_full A novel model for predicting immunotherapy response and prognosis in NSCLC patients
title_fullStr A novel model for predicting immunotherapy response and prognosis in NSCLC patients
title_full_unstemmed A novel model for predicting immunotherapy response and prognosis in NSCLC patients
title_short A novel model for predicting immunotherapy response and prognosis in NSCLC patients
title_sort novel model for predicting immunotherapy response and prognosis in nsclc patients
topic Non-small cell lung cancer
Predictive biomarkers
Immune checkpoint inhibitors
Machine learning
url https://doi.org/10.1186/s12935-025-03800-3
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