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Diagnostic Pathology
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Open Access 01-12-2023 | NSCLC | Research

Molecular profiling and prognostic biomarkers in chinese non-small cell lung cancer cohort

Authors: Fangfang Shen, Wei Guo, Xia Song, Bei Wang

Published in: Diagnostic Pathology | Issue 1/2023

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Abstract

Introduction

Comprehensive information about the genome analysis and its prognostic values of NSCLC patients in Chinese population are still needed.

Patients

A total of 117 Chinese patients with NSCLC were enrolled in this study. Tumor tissues or blood were collected and sequenced by targeted next-generation sequencing of 556 cancer related genes. The associations between clinical outcomes and clinical characteristics, TMB, mutated genes, treatment therapies were analyzed using Kaplan-Meier methods and further evaluated using multivariable Cox proportional hazards regression model.

Results

A total of 899 mutations were identified by targeted NGS. The most frequently mutations included EGFR (47%), TP53 (46%), KRAS (18%), LRP1B (12%) and SPTA1 (10%). Patients with mutant TP53, PREX2, ARID1A, PTPRT and PIK3CG had lower median overall survival (OS) than those patients with wild-type (P = 0.0056, P < 0.001, P < 0.0001, P < 0.0001 and P = 0.036, respectively). Using a multivariate Cox regression model, PREX2 (P < 0.001), ARID1A (P < 0.001) and PIK3CG (P = 0.04) were independent prognostic factors in NSCLC. In the patients received chemotherapy, squamous patients had a significantly longer median OS than adenocarcinoma patients (P = 0.011). In the patients received targeted therapy, adenocarcinoma patients had a significantly longer survival period than squamous patients (P = 0.01).

Conclusions

Our study provided comprehensive genomic alterations in a cohort of Chinese NSCLC. We also identified new prognostic biomarkers, which could provide potential clues for targeted therapies.
Appendix
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Literature
1.
Siegel RL, Miller KD, Fuchs HE, et al. Cancer Statistics, 2021. CA Cancer J Clin 2021;71:7–33.PubMed
2.
Zhang S, Sun K, Zheng R, et al. Cancer incidence and mortality in China, 2015. Journal of the National Cancer Center 2021;1:2–11.CrossRef
3.
Zheng S, Wang X, Fu Y, et al. Targeted next-generation sequencing for cancer-associated gene mutation and copy number detection in 206 patients with non-small-cell lung cancer. Bioengineered 2021;12:791–802.PubMedPubMedCentralCrossRef
4.
Wang L, Zhao D, Qin K, et al. Effect and biomarker of Nivolumab for non-small-cell lung cancer. Biomed Pharmacother 2019;117:109199.PubMedCrossRef
5.
6.
Blons H, Garinet S, Laurent-Puig P, et al. Molecular markers and prediction of response to immunotherapy in non-small cell lung cancer, an update. J Thorac Dis 2019;11:S25-s36.PubMedPubMedCentralCrossRef
7.
Cao J, Chen L, Li H, et al. An accurate and comprehensive clinical sequencing assay for Cancer targeted and Immunotherapies. Oncologist 2019;24:e1294-e1302.PubMedPubMedCentralCrossRef
8.
9.
Teixeira VH, Pipinikas CP, Pennycuick A, et al. Deciphering the genomic, epigenomic, and transcriptomic landscapes of pre-invasive lung cancer lesions. Nat Med 2019;25:517–525.PubMedCrossRef
10.
Nikiforova MN, Wald AI, Roy S, et al. Targeted next-generation sequencing panel (ThyroSeq) for detection of mutations in thyroid cancer. J Clin Endocrinol Metab 2013;98:E1852-60.PubMedCrossRef
11.
12.
Han SW, Kim HP, Shin JY, et al. Targeted sequencing of cancer-related genes in colorectal cancer using next-generation sequencing. PLoS One 2013;8:e64271.PubMedPubMedCentralCrossRef
13.
Cai H, Jing C, Chang X, et al. Mutational landscape of gastric cancer and clinical application of genomic profiling based on target next-generation sequencing. J Transl Med 2019;17:189.PubMedPubMedCentralCrossRef
14.
15.
Zhao S, Zhang Z, Zhan J, et al. Utility of comprehensive genomic profiling in directing treatment and improving patient outcomes in advanced non-small cell lung cancer. BMC Med 2021;19:223.PubMedPubMedCentralCrossRef
16.
Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129–39.PubMedCrossRef
17.
Paez JG, Jänne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004;304:1497–500.PubMedCrossRef
18.
Pao W, Miller V, Zakowski M, et al. EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A 2004;101:13306–11.PubMedPubMedCentralCrossRef
19.
Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005;353:123–32.PubMedCrossRef
20.
Ramalingam SS, Vansteenkiste J, Planchard D, et al. Overall survival with Osimertinib in untreated, EGFR-Mutated Advanced NSCLC. N Engl J Med 2020;382:41–50.PubMedCrossRef
21.
22.
23.
Seto T, Kiura K, Nishio M, et al. CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study): a single-arm, open-label, phase 1–2 study. Lancet Oncol 2013;14:590–8.PubMedCrossRef
24.
25.
Shaw AT, Kim TM, Crinò L, et al. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol 2017;18:874–886.PubMedCrossRef
26.
Horn L, Infante JR, Reckamp KL, et al. Ensartinib (X-396) in ALK-Positive Non-Small Cell Lung Cancer: results from a first-in-human phase I/II, Multicenter Study. Clin Cancer Res 2018;24:2771–2779.PubMedPubMedCentralCrossRef
27.
28.
29.
Shaw AT, Riely GJ, Bang YJ, et al. Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001. Ann Oncol 2019;30:1121–1126.PubMedPubMedCentralCrossRef
30.
Awad MM, Oxnard GR, Jackman DM, et al. MET exon 14 mutations in Non-Small-Cell Lung Cancer are Associated with Advanced Age and Stage-Dependent MET genomic amplification and c-Met overexpression. J Clin Oncol 2016;34:721–30.PubMedCrossRef
31.
Ardeshir-Larijani F, Bhateja P, Lipka MB, et al. KMT2D mutation is Associated with Poor Prognosis in Non-Small-Cell Lung Cancer. Clin Lung Cancer 2018;19:e489-e501.PubMedCrossRef
32.
McGowan M, Hoven AS, Lund-Iversen M, et al. PIK3CA mutations as prognostic factor in squamous cell lung carcinoma. Lung Cancer 2017;103:52–57.PubMedCrossRef
33.
Chin L, Andersen JN, Futreal PA. Cancer genomics: from discovery science to personalized medicine. Nat Med 2011;17:297–303.PubMedCrossRef
34.
35.
Xie J, Yao W, Chen L, et al. Plasma ctDNA increases tissue NGS-based detection of therapeutically targetable mutations in lung cancers. BMC Cancer 2023;23:294.PubMedPubMedCentralCrossRef
36.
McKenna A, Hanna M, Banks E, et al. The genome analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 2010;20:1297–303.PubMedPubMedCentralCrossRef
37.
Koboldt DC, Chen K, Wylie T, et al. VarScan: variant detection in massively parallel sequencing of individual and pooled samples. Bioinformatics 2009;25:2283–5.PubMedPubMedCentralCrossRef
38.
39.
Jordan EJ, Kim HR, Arcila ME, et al. Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies. Cancer Discov 2017;7:596–609.PubMedPubMedCentralCrossRef
40.
Rosell R, Bivona TG, Karachaliou N. Genetics and biomarkers in personalisation of lung cancer treatment. Lancet 2013;382:720–31.PubMedCrossRef
41.
Singal G, Miller PG, Agarwala V, et al. Association of patient characteristics and Tumor Genomics with Clinical Outcomes among patients with Non-Small Cell Lung Cancer using a clinicogenomic database. Jama 2019;321:1391–1399.PubMedPubMedCentralCrossRef
42.
Comprehensive molecular Profiling of lung adenocarcinoma. Nature 2014;511:543–50.CrossRef
43.
Hagemann IS, Devarakonda S, Lockwood CM, et al. Clinical next-generation sequencing in patients with non-small cell lung cancer. Cancer 2015;121:631–9.PubMedCrossRef
44.
Liu L, Liu J, Shao D, et al. Comprehensive genomic profiling of lung cancer using a validated panel to explore therapeutic targets in east asian patients. Cancer Sci 2017;108:2487–2494.PubMedPubMedCentralCrossRef
45.
Toh CK, Wong EH, Lim WT, et al. The impact of smoking status on the behavior and survival outcome of patients with advanced non-small cell lung cancer: a retrospective analysis. Chest 2004;126:1750–6.PubMedCrossRef
46.
La Fleur L, Falk-Sörqvist E, Smeds P, et al. Mutation patterns in a population-based non-small cell lung cancer cohort and prognostic impact of concomitant mutations in KRAS and TP53 or STK11. Lung Cancer 2019;130:50–58.PubMedCrossRef
47.
Kosaka T, Yatabe Y, Onozato R, et al. Prognostic implication of EGFR, KRAS, and TP53 gene mutations in a large cohort of japanese patients with surgically treated lung adenocarcinoma. J Thorac Oncol 2009;4:22–9.PubMedCrossRef
48.
Shen R, Martin A, Ni A, et al. Harnessing clinical sequencing data for survival stratification of patients with metastatic lung adenocarcinomas. JCO Precis Oncol 2019;3.
49.
50.
51.
Saleh MM, Scheffler M, Merkelbach-Bruse S, et al. Comprehensive analysis of TP53 and KEAP1 mutations and their impact on Survival in localized- and Advanced-Stage NSCLC. Journal of Thoracic Oncology 2022;17:76–88.PubMedCrossRef
52.
Jiao XD, Qin BD, You P, et al. The prognostic value of TP53 and its correlation with EGFR mutation in advanced non-small cell lung cancer, an analysis based on cBioPortal data base. Lung Cancer 2018;123:70–75.PubMedCrossRef
53.
Molina-Vila MA, Bertran-Alamillo J, Gascó A, et al. Nondisruptive p53 mutations are associated with shorter survival in patients with advanced non-small cell lung cancer. Clin Cancer Res 2014;20:4647–59.PubMedCrossRef
54.
Labbé C, Cabanero M, Korpanty GJ, et al. Prognostic and predictive effects of TP53 co-mutation in patients with EGFR-mutated non-small cell lung cancer (NSCLC). Lung Cancer 2017;111:23–29.PubMedCrossRef
55.
Nishio M, Koshikawa T, Kuroishi T, et al. Prognostic significance of abnormal p53 accumulation in primary, resected non-small-cell lung cancers. J Clin Oncol 1996;14:497–502.PubMedCrossRef
56.
57.
58.
59.
Zhu Y, Yan C, Wang X, et al. Pan-cancer analysis of ARID family members as novel biomarkers for immune checkpoint inhibitor therapy. Cancer Biol Ther 2022;23:104–111.PubMedPubMedCentralCrossRef
60.
Chen C, Liu H, Xu Q, et al. Association of PTPRT mutations with Cancer metastasis in multiple Cancer types. Biomed Res Int 2022;2022:9386477.PubMedPubMedCentral
61.
Zhang W, Shi F, Kong Y, et al. Association of PTPRT mutations with immune checkpoint inhibitors response and outcome in melanoma and non-small cell lung cancer. Cancer Med 2022;11:676–691.PubMedCrossRef
62.
Wu W, Jia L, Zhang Y, et al. Exploration of the prognostic signature reflecting tumor microenvironment of lung adenocarcinoma based on immunologically relevant genes. Bioengineered 2021;12:7417–7431.PubMedPubMedCentralCrossRef
63.
Veluswamy R, Mack PC, Houldsworth J, et al. KRAS G12C-Mutant Non-Small Cell Lung Cancer: Biology, Developmental therapeutics, and Molecular Testing. J Mol Diagn 2021;23:507–520.PubMedCrossRef
64.
65.
Janne PA, Riely GJ, Gadgeel SM, et al. Adagrasib in Non-Small-Cell Lung Cancer harboring a KRAS(G12C) mutation. N Engl J Med 2022;387:120–131.PubMedCrossRef
66.
Arbour KC, Jordan E, Kim HR, et al. Effects of co-occurring genomic alterations on outcomes in patients with KRAS-Mutant Non-Small Cell Lung Cancer. Clin Cancer Res 2018;24:334–340.PubMedCrossRef
67.
Wang M, Herbst RS, Boshoff C. Toward personalized treatment approaches for non-small-cell lung cancer. Nat Med 2021;27:1345–1356.PubMedCrossRef
68.
Bar-Sagi D, Knelson EH, Sequist LV. A bright future for KRAS inhibitors. Nat Cancer 2020;1:25–27.PubMedCrossRef
69.
Li T, Kung HJ, Mack PC, et al. Genotyping and genomic profiling of non-small-cell lung cancer: implications for current and future therapies. J Clin Oncol 2013;31:1039–49.PubMedPubMedCentralCrossRef
70.
Drilon A, Cappuzzo F, Ou SI, et al. Targeting MET in Lung Cancer: will expectations finally be MET? J Thorac Oncol 2017;12:15–26.PubMedCrossRef
Metadata
Title
Molecular profiling and prognostic biomarkers in chinese non-small cell lung cancer cohort
Authors
Fangfang Shen
Wei Guo
Xia Song
Bei Wang
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2023
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/s13000-023-01349-1

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