The predictive value of YAP-1 and POU2F3 for the efficacy of immuno-chemotherapy in extensive-stage SCLC patients

• Published in: Cancer treatment and research communications 2023, Vol.35, p.100684-100684, Article 100684
• Main Authors: Chen, Yu-Qing, Gao, Ling-Ling, Kong, Ling-Cong, Guan, Xu-Hui, Yang, Huan, Li, Yu-Fa, Lv, Zhi-Yi, Zhang, Xu-Chao, Liang, Hui-Ying, Chen, Hua-Jun, Wu, Yi-Long, Huang, Jie, Yang, Jin-Ji
• Format: Article
• Language: English
• Subjects: ECT; Humans; Immunotherapy; Lung Neoplasms - drug therapy; Nuclear Proteins; Octamer Transcription Factors; POU2F3; Prospective Studies; Retrospective Studies; Small Cell Lung Carcinoma - drug therapy; Small-cell lung cancer; YAP-1; YAP-Signaling Proteins
• ISSN: 2468-2942; 2468-2942
• DOI: 10.1016/j.ctarc.2023.100684

•The expression level of YAP-1 conducted by IHC was negatively correlated with the efficacy of ECT regimen in advanced small-cell lung cancer.•POU2F3 did not show a correlation to the efficacy of ECT regimen in advanced small-cell lung cancer.•IHC of YAP-1 may have the potential to use in clinical practice to predict the efficacy of chemo-immunotherapy for small-cell lung cancer patients. Recently, several clinical trials of immunotherapy for extensive-stage small-cell lung cancer (ES-SCLC) have shown limited benefits because of unselected patients. Thus, we aimed to explore whether YES-associated protein 1 (YAP-1) and POU domain class 2 transcription factor 3 (POU2F3) could identify SCLC patients with durable benefits from immunotherapy as potential biomarkers. We performed IHC of YAP-1 and POU2F3, and RNA-seq on tissues of ES- SCLC patients. An open-source plugin based on IHC-profiler was conducted to calculate the expression levels of YAP-1 and POU2F3. Patients with ES-SCLC were retrospectively investigated in the Guangdong Provincial People's Hospital from January 2018 to July 2021, and 21 patients whoever received atezolizumab plus etoposide/carboplatin (ECT) regimen also had tissue samples reachable. The median IHC-score of YAP-1 in responders (CR/PR patients) was significantly lower than in nonresponders (SD/PD patients) at 13.97 (95% CI: 8.97–16.30) versus 23.72 (95% CI: 8.13–75.40). The IHC-score of YAP-1 and PFS showed a negative correlation by Spearman (r=-0.496). However, POU2F3 did not show a correlation with efficacy. Besides, patients with YAP-1 high expression had IL6, MYCN, and MYCT1 upregulated, while analysis of immune cell infiltration only showed that M0 macrophages were significantly higher. The expression of YAP-1 negatively correlated with the efficacy of ECT in ES-SCLC patients while POU2F3 did not reveal the predictive value. However, prospective investigations with a large sample size are needed.