Identification and Exploration of Serine Peptidase Inhibitor Kazal Type I (SPINK1) as a Potential Biomarker Correlated with the Progression of Non-Small Cell Lung Cancer

Cell Biochem Biophys. 2022 Dec;80(4):807-818. doi: 10.1007/s12013-022-01098-w. Epub 2022 Oct 4.

Abstract

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Although significant advances have been achieved in the treatment of NSCLC during the past two decades, the 5-year survival rate of patients with NSCLC remains <20%. Thus, there is an urgent requirement to further understand the molecular mechanisms that promote NSCLC development and to identify novel therapeutic targets. In the present study, the gene expression profiles of patients with NSCLC from The Cancer Genome Atlas database were carefully analyzed and SPINK1 was identified as a tumor-inducing factor. SPINK1 expression level was found to be increased in both NSCLC tissues and cell lines. Moreover, SPINK1 promoted cell proliferation in A549 and H1299 cells. Knockdown of SPINK1 could activate cell autophagy and apoptosis. Mechanistically, SPINK1 was demonstrated to induce the proliferation of NSCLC via activating the MEK/ERK signaling pathway. In conclusion, these findings suggested that SPINK1 may serve as a potential biomarker in NSCLC.

Keywords: NSCLC; Proliferation; SPINK1; Signaling pathway.

MeSH terms

  • Biomarkers
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms* / genetics
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Protease Inhibitors
  • Serine / metabolism
  • Trypsin Inhibitor, Kazal Pancreatic / genetics
  • Trypsin Inhibitor, Kazal Pancreatic / metabolism

Substances

  • Biomarkers
  • Protease Inhibitors
  • SPINK1 protein, human
  • Serine
  • Trypsin Inhibitor, Kazal Pancreatic
  • Mitogen-Activated Protein Kinase Kinases