Clinical Features and Prognostic Biomarkers in Patients with -mutated Non-small Cell Lung Cancer

Overview

Journal Transl Lung Cancer Res

Date 2024 Sep 12

PMID 39263013

Authors

Jinyu Long

Ying Chen

Xingguang Luo

Ruiying Rao

Chenxi Wang

Yuxin Guo

Jinhe Xu

Ping Lin

Yingfang Song

Lijuan Qu

Qinghong Liu

Jun Lu

Chengzhi Zhou

Zhengbo Song

Xiandong Lin

Hiroyuki Adachi

Jacek Jassem

Masatsugu Hamaji

Zongyang Yu

Affiliations

Soon will be listed here.

Abstract

Background: Patients with non-small cell lung cancer (NSCLC) carrying mutations (-Mut) tend to have more advanced disease and a poor prognosis. However, due to the rarity of this mutation and the lack of related studies, the characteristics of -Mut NSCLC patients remains poorly determined. To clarify the clinical characteristics and prognostic factors of -Mut NSCLC, we initiated the present study to provide a clinical reference.

Methods: We used data from two cohorts of NSCLC--mutated samples: The Cancer Genome Atlas (TCGA) database and our center's clinical data. The TCGA database was used to obtain 481 NSCLC--Mut samples for clinical characterization. The center collected data on 224 consecutive NSCLC patients treated between December 2020 to July 2022. Among them, 26 harbored mutations, and 20 were eligible for inclusion in the study. Clinical, pathological, and molecular features, as well as prognostic role of mutations were analyzed. Additionally, we analyzed the prognostic impact of Napsin A expression in -Mut patients.

Results: The TCGA database included 480 patients with -Mut NSCLC, 311 males (64.8%) and 169 females (35.2%), with a median age of 67 years. Among the 20 -Mut patients in our center series, 12 (60%) were males and 8 (40%) females, with a median age of 63. The intergroup prognostic correlation analysis showed that -Mut patients had significantly worse prognosis than those the wild-type (-WT) (P=0.04). Within the -Mut group, patients with Napsin A expression had longer overall survival (OS) (P=0.03) than those without expression. Median survival in the Napsin A-positive and negative groups was 32 and 15 months, respectively. According to time-dependent receiver operating curve analysis, patients with Napsin A expression had significantly longer first-line treatment progression-free survival (PFS1) [area under the curve (AUC) =0.748] and OS (AUC =0.586). No prognostic value of Napsin A was found in patients -WT patients.

Conclusions: -Mut is an adverse prognostic feature in NSCLC patients. Napsin A expression in -Mut patients is associated with prolonged OS.

Citing Articles

/BRG1-deficient non-small cell lung cancer: clinical, imaging, pathological features, and follow-up results of 23 patients.

Wumener X, Ye X, Zhang Y, E T, Zhao J, Liang Y Transl Lung Cancer Res. 2025; 14(1):107-123.

PMID: 39958212 PMC: 11826276. DOI: 10.21037/tlcr-24-567.

References

Bray F, Laversanne M, Sung H, Ferlay J, Siegel R, Soerjomataram I . Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024; 74(3):229-263. DOI: 10.3322/caac.21834. View

Nambirajan A, Jain D . Recent updates in thoracic SMARCA4-deficient undifferentiated tumor. Semin Diagn Pathol. 2021; 38(5):83-89. DOI: 10.1053/j.semdp.2021.06.001. View

Deribe Y, Sun Y, Terranova C, Khan F, Martinez-Ledesma J, Gay J . Mutations in the SWI/SNF complex induce a targetable dependence on oxidative phosphorylation in lung cancer. Nat Med. 2018; 24(7):1047-1057. PMC: 6650267. DOI: 10.1038/s41591-018-0019-5. View

Li H, Gao J, Jin C, Jiang J, Ding J . Downregulation of SETBP1 promoted non-small cell lung cancer progression by inducing cellular EMT and disordered immune status. Am J Transl Res. 2020; 12(2):447-462. PMC: 7061827. View

Chen W, Zheng R, Baade P, Zhang S, Zeng H, Bray F . Cancer statistics in China, 2015. CA Cancer J Clin. 2016; 66(2):115-32. DOI: 10.3322/caac.21338. View

Tian Y, Xu L, Li X, Li H, Zhao M . SMARCA4: Current status and future perspectives in non-small-cell lung cancer. Cancer Lett. 2022; 554:216022. DOI: 10.1016/j.canlet.2022.216022. View

Mardinian K, Adashek J, Botta G, Kato S, Kurzrock R . : Implications of an Altered Chromatin-Remodeling Gene for Cancer Development and Therapy. Mol Cancer Ther. 2021; 20(12):2341-2351. PMC: 8643328. DOI: 10.1158/1535-7163.MCT-21-0433. View

Naito T, Udagawa H, Umemura S, Sakai T, Zenke Y, Kirita K . Non-small cell lung cancer with loss of expression of the SWI/SNF complex is associated with aggressive clinicopathological features, PD-L1-positive status, and high tumor mutation burden. Lung Cancer. 2019; 138:35-42. DOI: 10.1016/j.lungcan.2019.10.009. View

Li F, Wang S, Wang Y, Lv Z, Jin D, Yi H . Multi-omics analysis unravels the underlying mechanisms of poor prognosis and differential therapeutic responses of solid predominant lung adenocarcinoma. Front Immunol. 2023; 14:1101649. PMC: 9946976. DOI: 10.3389/fimmu.2023.1101649. View

10.

Schoenfeld A, Bandlamudi C, Lavery J, Montecalvo J, Namakydoust A, Rizvi H . The Genomic Landscape of Alterations and Associations with Outcomes in Patients with Lung Cancer. Clin Cancer Res. 2020; 26(21):5701-5708. PMC: 7641983. DOI: 10.1158/1078-0432.CCR-20-1825. View

11.

Jiao S, Zhang X, Wang D, Fu H, Xia Q . Genetic Alteration and Their Significance on Clinical Events in Small Cell Lung Cancer. Cancer Manag Res. 2022; 14:1493-1505. PMC: 9034895. DOI: 10.2147/CMAR.S356037. View

12.

Walter D, Venancio O, Buza E, Tobias J, Deshpande C, Gudiel A . Systematic Inactivation of Chromatin-Regulating Enzymes Identifies Setd2 as a Potent Tumor Suppressor in Lung Adenocarcinoma. Cancer Res. 2017; 77(7):1719-1729. PMC: 5380596. DOI: 10.1158/0008-5472.CAN-16-2159. View

13.

Zhu X, Fu Z, Chen S, Ong D, Aceto G, Ho R . Alanine supplementation exploits glutamine dependency induced by SMARCA4/2-loss. Nat Commun. 2023; 14(1):2894. PMC: 10199906. DOI: 10.1038/s41467-023-38594-3. View

14.

Relli V, Trerotola M, Guerra E, Alberti S . Abandoning the Notion of Non-Small Cell Lung Cancer. Trends Mol Med. 2019; 25(7):585-594. DOI: 10.1016/j.molmed.2019.04.012. View

15.

Concepcion C, Ma S, LaFave L, Bhutkar A, Liu M, DeAngelo L . Inactivation Promotes Lineage-Specific Transformation and Early Metastatic Features in the Lung. Cancer Discov. 2021; 12(2):562-585. PMC: 8831463. DOI: 10.1158/2159-8290.CD-21-0248. View

16.

Herbst R, Morgensztern D, Boshoff C . The biology and management of non-small cell lung cancer. Nature. 2018; 553(7689):446-454. DOI: 10.1038/nature25183. View

17.

Morrison A . Chromatin-remodeling links metabolic signaling to gene expression. Mol Metab. 2020; 38:100973. PMC: 7300377. DOI: 10.1016/j.molmet.2020.100973. View

18.

Carbone D, Gandara D, Antonia S, Zielinski C, Paz-Ares L . Non-Small-Cell Lung Cancer: Role of the Immune System and Potential for Immunotherapy. J Thorac Oncol. 2015; 10(7):974-84. PMC: 4618296. DOI: 10.1097/JTO.0000000000000551. View

19.

Chatzopoulos K, Boland J . Update on genetically defined lung neoplasms: NUT carcinoma and thoracic SMARCA4-deficient undifferentiated tumors. Virchows Arch. 2021; 478(1):21-30. DOI: 10.1007/s00428-020-03011-3. View

20.

Alessi J, Ricciuti B, Spurr L, Gupta H, Li Y, Glass C . SMARCA4 and Other SWItch/Sucrose NonFermentable Family Genomic Alterations in NSCLC: Clinicopathologic Characteristics and Outcomes to Immune Checkpoint Inhibition. J Thorac Oncol. 2021; 16(7):1176-1187. DOI: 10.1016/j.jtho.2021.03.024. View