A prospective multi-cohort study identifies and validates a 5-gene peripheral blood signature predictive of immunotherapy response in non-small cell lung cancer

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2024年11月6日

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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

摘要

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.