A prospective multi-cohort study identifies and validates a 5-gene peripheral blood signature predictive of immunotherapy response in non-small cell lung cancer
Abstract Background Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape for non-small cell lung cancer (NSCLC). The variability in patient responses necessitates a blood-based, multi-cohort gene signature to predict ICI response in NSCLC. Methods We performed transcriptom...
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BMC
2024-11-01
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| Series: | Molecular Cancer |
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| Online Access: | https://doi.org/10.1186/s12943-024-02160-2 |
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| author | Shaoqiu Chen Fangfang Liu Yuanyuan Fu Chris K. Deng Jeffrey A. Borgia Abdul-Ghani Ayman Masaki Nasu Mayumi Jijiwa Hua Yang Ting Gong Junlong Wang Zhougui Ling Xiaoyan Wang Hongwei Wang Qian Chu Youping Deng |
| author_facet | Shaoqiu Chen Fangfang Liu Yuanyuan Fu Chris K. Deng Jeffrey A. Borgia Abdul-Ghani Ayman Masaki Nasu Mayumi Jijiwa Hua Yang Ting Gong Junlong Wang Zhougui Ling Xiaoyan Wang Hongwei Wang Qian Chu Youping Deng |
| author_sort | Shaoqiu Chen |
| collection | DOAJ |
| description | Abstract Background Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape for non-small cell lung cancer (NSCLC). The variability in patient responses necessitates a blood-based, multi-cohort gene signature to predict ICI response in NSCLC. Methods We performed transcriptomic profiling of peripheral blood mononuclear cell (PBMC) and buffy coat (BC) samples from three independent cohorts of NSCLC patients treated with ICIs: a retrospective cohort (PMBCR, n = 59), a retrospective validation cohort (BC, n = 44), and a prospective validation cohort (PBMCP, n = 42). We identified a 5-gene signature (UQCRB, NDUFA3, CDKN2D, FMNL1-DT, and APOL3) predictive of ICI response and validated its clinical utility in the prospective PBMCP cohort. Response was evaluated using RECIST criteria, and patients were followed up for progression-free survival (PFS) and overall survival (OS). Results In the prospective PBMCP cohort, the 5-gene signature demonstrated high accuracy in stratifying patients into responders and non-responders (AUC = 0.89, 95% CI: 0.80–0.99). Predicted responders exhibited significantly longer PFS compared to predicted non-responders (median: 13.8 months vs. 4.2 months, HR = 0.21, 95% CI: 0.07–0.58, p = 0.005). Conclusion Our study confirms a 5-gene signature as a key biomarker for ICI response in NSCLC, enhancing treatment precision. |
| format | Article |
| id | doaj-art-91bd677c82d3492abc8d495bd1435c09 |
| institution | DOAJ |
| issn | 1476-4598 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj-art-91bd677c82d3492abc8d495bd1435c092025-08-20T02:50:05ZengBMCMolecular Cancer1476-45982024-11-012311510.1186/s12943-024-02160-2A prospective multi-cohort study identifies and validates a 5-gene peripheral blood signature predictive of immunotherapy response in non-small cell lung cancerShaoqiu Chen0Fangfang Liu1Yuanyuan Fu2Chris K. Deng3Jeffrey A. Borgia4Abdul-Ghani Ayman5Masaki Nasu6Mayumi Jijiwa7Hua Yang8Ting Gong9Junlong Wang10Zhougui Ling11Xiaoyan Wang12Hongwei Wang13Qian Chu14Youping Deng15Department of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii at ManoaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii at ManoaDepartment of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii at ManoaDiagnostic Radiology, Rush University Medical CenterDepartment of Surgery, John A. Burns School of Medicine, University of Hawaii and Research Laboratory at the Queen’s Medical CenterDepartment of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii at ManoaDepartment of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii at ManoaDepartment of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii at ManoaDepartment of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii at ManoaDepartment of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii at ManoaDepartment of Pulmonary and Critical Care Medicine, the Fourth Affiliated Hospital of Guangxi Medical UniversityKey Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong UniversitySchool of Pharmacy, Nanjing Medical UniversityDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii at ManoaAbstract Background Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape for non-small cell lung cancer (NSCLC). The variability in patient responses necessitates a blood-based, multi-cohort gene signature to predict ICI response in NSCLC. Methods We performed transcriptomic profiling of peripheral blood mononuclear cell (PBMC) and buffy coat (BC) samples from three independent cohorts of NSCLC patients treated with ICIs: a retrospective cohort (PMBCR, n = 59), a retrospective validation cohort (BC, n = 44), and a prospective validation cohort (PBMCP, n = 42). We identified a 5-gene signature (UQCRB, NDUFA3, CDKN2D, FMNL1-DT, and APOL3) predictive of ICI response and validated its clinical utility in the prospective PBMCP cohort. Response was evaluated using RECIST criteria, and patients were followed up for progression-free survival (PFS) and overall survival (OS). Results In the prospective PBMCP cohort, the 5-gene signature demonstrated high accuracy in stratifying patients into responders and non-responders (AUC = 0.89, 95% CI: 0.80–0.99). Predicted responders exhibited significantly longer PFS compared to predicted non-responders (median: 13.8 months vs. 4.2 months, HR = 0.21, 95% CI: 0.07–0.58, p = 0.005). Conclusion Our study confirms a 5-gene signature as a key biomarker for ICI response in NSCLC, enhancing treatment precision.https://doi.org/10.1186/s12943-024-02160-2ICIsPredictive biomarkersNSCLCClinical utilityBlood-based |
| spellingShingle | Shaoqiu Chen Fangfang Liu Yuanyuan Fu Chris K. Deng Jeffrey A. Borgia Abdul-Ghani Ayman Masaki Nasu Mayumi Jijiwa Hua Yang Ting Gong Junlong Wang Zhougui Ling Xiaoyan Wang Hongwei Wang Qian Chu Youping Deng A prospective multi-cohort study identifies and validates a 5-gene peripheral blood signature predictive of immunotherapy response in non-small cell lung cancer Molecular Cancer ICIs Predictive biomarkers NSCLC Clinical utility Blood-based |
| title | A prospective multi-cohort study identifies and validates a 5-gene peripheral blood signature predictive of immunotherapy response in non-small cell lung cancer |
| title_full | A prospective multi-cohort study identifies and validates a 5-gene peripheral blood signature predictive of immunotherapy response in non-small cell lung cancer |
| title_fullStr | A prospective multi-cohort study identifies and validates a 5-gene peripheral blood signature predictive of immunotherapy response in non-small cell lung cancer |
| title_full_unstemmed | A prospective multi-cohort study identifies and validates a 5-gene peripheral blood signature predictive of immunotherapy response in non-small cell lung cancer |
| title_short | A prospective multi-cohort study identifies and validates a 5-gene peripheral blood signature predictive of immunotherapy response in non-small cell lung cancer |
| title_sort | prospective multi cohort study identifies and validates a 5 gene peripheral blood signature predictive of immunotherapy response in non small cell lung cancer |
| topic | ICIs Predictive biomarkers NSCLC Clinical utility Blood-based |
| url | https://doi.org/10.1186/s12943-024-02160-2 |
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