An immune-related lncRNA signature predicts prognosis and adjuvant chemotherapeutic response in patients with small-cell lung cancer

Author:

Zhang Zhihui,Luo Yuejun,Zhang Chaoqi,Wu Peng,Zhang Guochao,Zeng Qingpeg,Wang Lide,Xue Liyan,Yang Zhaoyang,Zeng Hua,Zheng Bo,Tan Fengwei,Xue Qi,Gao Shugeng,Sun Nan,He JieORCID

Abstract

Abstract Background Patients with small-cell lung cancer (SCLC) are burdened by limited treatment options and the disease’s dismal prognosis. Long non-coding RNAs (lncRNAs) are essential regulators of genetic alteration and are actively involved in tumor immunity. However, few studies have examined interactions between immune genes and lncRNAs in SCLC. Methods Immune-related lncRNA (irlncRNA) expression profiles and their clinical significance were explored. We enrolled 227 patients with SCLC, including 79 cases from GSE65002 and 148 cases from a validation cohort with corresponding qPCR data. The least absolute shrinkage and selection operator (LASSO) model was applied to identify prognostic irlncRNAs for an irlncRNA-based SCLC signature. We additionally investigated the potential mechanisms and immune landscape of the signature using bioinformatics methods. Results An irlncRNA signature including 8 irlncRNAs (ENOX1-AS1, AC005162, LINC00092, RPL34-AS1, AC104135, AC015971, AC126544, AP001189) was established for patients with SCLC in the training cohort. Low-risk patients were more likely to benefit from chemotherapy and achieve a favorable prognosis. The signature was also well-validated in the validation cohort and various clinical subgroups. Compared to other clinical parameters, the irlncRNA signature exhibited superior predictive performance for chemotherapy response and prognosis. The signature was as an independent prognostic factor in the training and validation cohorts. Interestingly, low-risk patients showed an activated immune phenotype. Conclusion We constructed the first irlncRNA-based signature for chemotherapy efficacy and outcome prediction. The irlncRNA signature is a reliable and robust prognostic classifier that could be useful for clinical management and determination of potential chemotherapy benefit for patients with SCLC.

Funder

CAMS Innovation Fund for Medical Sciences

National Key R&D Program of China

National Natural Science Foundation of China

Fundamental Research Funds for the Central Universities

National Key Basic Research Development Plan

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Genetics,Oncology

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