Clinical significance and prospective mechanism of increased CDKN2A expression in small cell lung cancer

Clin Transl Oncol. 2024 Jun;26(6):1519-1531. doi: 10.1007/s12094-023-03376-2. Epub 2024 Jan 11.

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.

Keywords: Clinical significance; Cyclin dependent kinase inhibitor 2A; Immunohistochemistry; Kaplan–Meier survival analysis; Small cell lung cancer.

MeSH terms

  • Aged
  • Biomarkers, Tumor* / genetics
  • Biomarkers, Tumor* / metabolism
  • Case-Control Studies
  • Clinical Relevance
  • Cyclin-Dependent Kinase Inhibitor p16* / metabolism
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • ROC Curve
  • Small Cell Lung Carcinoma* / genetics
  • Small Cell Lung Carcinoma* / metabolism
  • Small Cell Lung Carcinoma* / mortality
  • Small Cell Lung Carcinoma* / pathology
  • Survival Rate

Substances

  • CDKN2A protein, human