BACKGROUND: Genetic mutations are quite common in non-small cell lung cancer (NSCLC), however, their prognostic value remains controversial. METHODS: This study explored the mutational landscape of tumor samples from patients with advanced NSCLC by next-generation sequencing (NGS). A total of 101 NSCLC patients in stage III or IV receiving first-line treatment were included. RESULTS: TP53 mutation was the most frequent genetic alteration in NSCLC tumors (68%), followed by EGFR (49%), CDKN2A (12%), LRP1B (9%), and FAT3 (9%) mutations. Among 85 patients with stage IV NSCLC, first-line targeted therapy remarkably prolonged progression-free survival (PFS) of patients compared with first-line chemotherapy (p = 0.0028). Among 65 patients with stage IV NSCLC whose tumors harbored EGFR, ALK, ROS, or BRAF mutations, first-line targeted therapy substantially prolonged the PFS of patients (p = 0.0027). In patients with TP53 mutations who received first-line targeted therapy or chemotherapy, missense mutation was the most common mutation type (36/78), and exon 5 represented the most common mutated site (16/78). CONCLUSIONS: TP53 mutation in exon 5 could independently predict poor PFS of patients with stage IV NSCLC after the first- line treatment. Moreover, mutations in TP53 exon 5 and LRP1B were associated with shorter PFS of such patients whether after first-line chemotherapy or targeted therapy, respectively. Thus, these patients should be given immunotherapy or immunochemotherapy.
Author Info:
(1) Cancer Institute and Hospital, Department of Immunology, Tianjin Medical University, 300060 Tianjin, China. National Clinical Research Center for Cancer, 300060 Tianjin, China.
Key Laboratory of Cancer Prevention and Therapy, 300060 Tianjin, China. Tianjin's Clinical Research Center for Cancer, 300060 Tianjin, China. Key Laboratory of Cancer Immunology and Biotherapy, 300060 Tianjin, China. Department of Thoracic Oncology, Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, 030032 Taiyuan, Shanxi, China. Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, Hubei, China. (2) Cancer Institute and Hospital, Department of Immunology, Tianjin Medical University, 300060 Tianjin, China. National Clinical Research Center for Cancer, 300060 Tianjin, China. Key Laboratory of Cancer Prevention and Therapy, 300060 Tianjin, China. Tianjin's Clinical Research Center for Cancer, 300060 Tianjin, China. Key Laboratory of Cancer Immunology and Biotherapy, 300060 Tianjin, China. Department of Thoracic Oncology, Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, 030032 Taiyuan, Shanxi, China. (3) Cancer Institute and Hospital, Department of Immunology, Tianjin Medical University, 300060 Tianjin, China. (4) Institute of Biotechnology, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, 030006 Taiyuan, Shanxi, China. (5) Cancer Institute and Hospital, Department of Immunology, Tianjin Medical University, 300060 Tianjin, China. (6) Genetron Health Inc, 102206 Beijing, China. (7) Genetron Health Inc, 102206 Beijing, China. (8) Department of Thoracic Oncology, Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, 030032 Taiyuan, Shanxi, China. Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, Hubei, China. (9) Department of Thoracic Oncology, Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, 030032 Taiyuan, Shanxi, China. Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, Hubei, China. (10) Department of Molecular Biology, Shanxi Cancer Hospital; Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences; Cancer Hospital Affiliated to Shanxi Medical University, 030012 Taiyuan, Shanxi, China. (11) Department of Thoracic Oncology, Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, 030032 Taiyuan, Shanxi, China. Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, Hubei, China. (12) Cancer Institute and Hospital, Department of Immunology, Tianjin Medical University, 300060 Tianjin, China. National Clinical Research Center for Cancer, 300060 Tianjin, China. Key Laboratory of Cancer Prevention and Therapy, 300060 Tianjin, China. Tianjin's Clinical Research Center for Cancer, 300060 Tianjin, China. Key Laboratory of Cancer Immunology and Biotherapy, 300060 Tianjin, China. Department of Biotherapy, Cancer Institute and Hospital, 300060 Tianjin, China.
Citation: Front Biosci (Landmark Ed) 2023 Jul 24 28:147 Epub
