Mutations in the DNA polymerase binding pathway affect the immune microenvironment of patients with small‐cell lung cancer and enhance the efficacy of platinum‐based chemotherapy

Author:

Lin Anqi1,Mou Weiming123,Zhu Lingxuan24,Yang Tao25,Zhou Chaozheng2,Zhang Jian1,Luo Peng1ORCID

Affiliation:

1. Department of Oncology, Zhujiang Hospital Southern Medical University Guangzhou Guangdong China

2. The First Clinical Medical School Southern Medical University Guangzhou Guangdong China

3. Department of Urology, Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai China

4. Department of Etiology and Carcinogenesis National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China

5. Department of Medical Oncology National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China

Abstract

AbstractBackgroundSmall‐cell lung cancer (SCLC) is characterized by its high malignancy and is associated with a poor prognosis. In the early stages of the disease, platinum‐based chemotherapy is the recommended first‐line treatment and has demonstrated efficacy. However, SCLC is prone to recurrence and is generally resistant to chemotherapy in its later stages.MethodsHere, we collected samples from SCLC patients who received platinum‐based chemotherapy, performed genomic and transcriptomic analyses, and validated our results with publicly available data.ResultsSCLC patients with DNA polymerase binding pathway mutations had an improved prognosis after platinum chemotherapy compared with patients without such mutations. Patients in the mutant (MT) group had higher infiltration of T cells, B cells, and M1 macrophages compared with patients without DNA polymerase binding pathway mutations.ConclusionsDNA polymerase binding pathway mutations can be used as prognostic markers for platinum‐based chemotherapy in SCLC.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Guangdong Province

Publisher

Wiley

Subject

Pharmacology (medical),Cancer Research,Pharmacology, Toxicology and Pharmaceutics (miscellaneous),Drug Discovery,Oncology

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