Clinical Significance and Prospective Mechanism of Increased CDKN2A Expression in Small Cell Lung Cancer

Overview

Journal Clin Transl Oncol

Specialty Oncology

Date 2024 Jan 11

PMID 38206516

Authors

Dong-Ming Li

Guo-Sheng Li

Jian-Di Li

Feng Chen

Hong Huang

Wan-Ying Huang

Zhi-Guang Huang

Yi-Wu Dang

Yu-Lu Tang

Zhong-Qing Tang

Wen-Jia Tang

Gang Chen

Hui-Ping Lu

Affiliations

Soon will be listed here.

Abstract

Background: Although it has been shown that cyclin dependent kinase inhibitor 2A (CDKN2A) plays a significant role in a number of malignancies, its clinicopathological value and function in small cell lung cancer (SCLC) is unclear and warrants additional research.

Methods: The clinical significance of CDKN2A expression in SCLC was examined by multiple methods, including comprehensive integration of mRNA level by high throughput data, Kaplan-Meier survival analysis for prognostic value, and validation of its protein expression using in-house immunohistochemistry.

Results: The expression of CDKN2A mRNA in 357 cases of SCLC was evidently higher than that in the control group (n = 525) combing the data from 20 research centers worldwide. The standardized mean difference (SMD) was 3.07, and the area under the curve (AUC) of summary receiver operating characteristic curve (sROC) was 0.97 for the overexpression of CDKN2A. ACC, COAD, KICH, KIRC, PCPG, PRAD, UCEC, UVM patients with higher CDKN2A expression had considerably worse overall survival rates than those with lower CDKN2A expression with the hazard ratio (HR) > 1.

Conclusion: CDKN2A upregulation extensively enhances the carcinogenesis and progression of SCLC.

Citing Articles

Epigenetic modifications in early stage lung cancer: pathogenesis, biomarkers, and early diagnosis.

Bi L, Wang X, Li J, Li W, Wang Z MedComm (2020). 2025; 6(3):e70080.

PMID: 39991629 PMC: 11843169. DOI: 10.1002/mco2.70080.

References

Zhou Y, Wang X, Qiu X, Zhang S, Wang C, Zheng F . CDKN2A promoter methylation and hepatocellular carcinoma risk: A meta-analysis. Clin Res Hepatol Gastroenterol. 2018; 42(6):529-541. DOI: 10.1016/j.clinre.2017.07.003. View

Yu G, Wang L, Han Y, He Q . clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012; 16(5):284-7. PMC: 3339379. DOI: 10.1089/omi.2011.0118. View

Ritchie M, Phipson B, Wu D, Hu Y, Law C, Shi W . limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015; 43(7):e47. PMC: 4402510. DOI: 10.1093/nar/gkv007. View

Qiao J, Tian Y, Cheng X, Liu Z, Zhou J, Gu L . Deletion Leading to Hematogenous Metastasis of Human Gastric Carcinoma. Front Oncol. 2022; 11:801219. PMC: 8733704. DOI: 10.3389/fonc.2021.801219. View

Chen P, Liu Y, Wen Y, Zhou C . Non-small cell lung cancer in China. Cancer Commun (Lond). 2022; 42(10):937-970. PMC: 9558689. DOI: 10.1002/cac2.12359. View

Duma N, Santana-Davila R, Molina J . Non-Small Cell Lung Cancer: Epidemiology, Screening, Diagnosis, and Treatment. Mayo Clin Proc. 2019; 94(8):1623-1640. DOI: 10.1016/j.mayocp.2019.01.013. View

Liu W, Zhuang C, Huang T, Yang S, Zhang M, Lin B . Loss of CDKN2A at chromosome 9 has a poor clinical prognosis and promotes lung cancer progression. Mol Genet Genomic Med. 2020; 8(12):e1521. PMC: 7767555. DOI: 10.1002/mgg3.1521. View

Chen Z, Guo Y, Zhao D, Zou Q, Yu F, Zhang L . Comprehensive Analysis Revealed that is a Biomarker for Immune Infiltrates in Multiple Cancers. Front Cell Dev Biol. 2022; 9:808208. PMC: 8733648. DOI: 10.3389/fcell.2021.808208. View

Leek J, Johnson W, Parker H, Jaffe A, Storey J . The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics. 2012; 28(6):882-3. PMC: 3307112. DOI: 10.1093/bioinformatics/bts034. View

10.

Oliver A . Lung Cancer: Epidemiology and Screening. Surg Clin North Am. 2022; 102(3):335-344. DOI: 10.1016/j.suc.2021.12.001. View

11.

Jiao Y, Feng Y, Wang X . Regulation of Tumor Suppressor Gene CDKN2A and Encoded p16-INK4a Protein by Covalent Modifications. Biochemistry (Mosc). 2018; 83(11):1289-1298. DOI: 10.1134/S0006297918110019. View

12.

Chan S, Chiang J, Ngeow J . CDKN2A germline alterations and the relevance of genotype-phenotype associations in cancer predisposition. Hered Cancer Clin Pract. 2021; 19(1):21. PMC: 7992806. DOI: 10.1186/s13053-021-00178-x. View

13.

Gutiontov S, Turchan W, Spurr L, Rouhani S, Chervin C, Steinhardt G . CDKN2A loss-of-function predicts immunotherapy resistance in non-small cell lung cancer. Sci Rep. 2021; 11(1):20059. PMC: 8501138. DOI: 10.1038/s41598-021-99524-1. View

14.

Muss H, Smitherman A, Wood W, Nyrop K, Tuchman S, Randhawa P . p16 a biomarker of aging and tolerance for cancer therapy. Transl Cancer Res. 2022; 9(9):5732-5742. PMC: 8797727. DOI: 10.21037/tcr.2020.03.39. View

15.

Merkle J, Breunig M, Schmid M, Allgower C, Kruger J, Melzer M . -Mutated Pancreatic Ductal Organoids from Induced Pluripotent Stem Cells to Model a Cancer Predisposition Syndrome. Cancers (Basel). 2021; 13(20). PMC: 8533699. DOI: 10.3390/cancers13205139. View

16.

Aftab A, Shahzad S, Hussain H, Khan R, Irum S, Tabassum S . CDKN2A/P16INK4A variants association with breast cancer and their in-silico analysis. Breast Cancer. 2018; 26(1):11-28. DOI: 10.1007/s12282-018-0894-0. View

17.

Luan Y, Zhang W, Xie J, Mao J . CDKN2A inhibits cell proliferation and invasion in cervical cancer through LDHA-mediated AKT/mTOR pathway. Clin Transl Oncol. 2020; 23(2):222-228. DOI: 10.1007/s12094-020-02409-4. View

18.

Thai A, Solomon B, Sequist L, Gainor J, Heist R . Lung cancer. Lancet. 2021; 398(10299):535-554. DOI: 10.1016/S0140-6736(21)00312-3. View

19.

Herzog B, Devarakonda S, Govindan R . Overcoming Chemotherapy Resistance in SCLC. J Thorac Oncol. 2021; 16(12):2002-2015. DOI: 10.1016/j.jtho.2021.07.018. View

20.

Serra S, Chetty R . . J Clin Pathol. 2018; 71(10):853-858. DOI: 10.1136/jclinpath-2018-205216. View