Cancer driver gene and non-coding RNA alterations as biomarkers of brain metastasis in lung cancer: A review of the literature

Biomed Pharmacother. 2021 Nov:143:112190. doi: 10.1016/j.biopha.2021.112190. Epub 2021 Sep 21.

Abstract

Brain metastasis (BM) is the most common event in patients with lung cancer. Despite multimodal treatments and advances in systemic therapies, development of BM remains one of the main factors associated with poor prognosis and mortality in patients with lung cancer. Therefore, better understanding of mechanisms involved in lung cancer brain metastasis (LCBM) is of great importance to suppress cancer cells and to improve the overall survival of patients. Several cancer-related genes such as EGFR and KRAS have been proposed as potential predictors of LCBM. In addition, there is ample evidence supporting crucial roles of non-coding RNAs (ncRNAs) in mediating LCBM. In this review, we provide comprehensive information on risk assessment, predictive, and prognostic panels for early detection of BM in patients with lung cancer. Moreover, we present an overview of LCBM molecular mechanisms, cancer driver genes, and ncRNAs which may predict the risk of BM in lung cancer patients. Recent clinical studies have focused on determining mechanisms involved in LCBM and their association with diagnosis, prognosis, and treatment outcomes. These studies have shown that alterations in EGFR, KRAS, BRAF, and ALK, as the most frequent coding gene alterations, and dysregulation of ncRNAs such as miR-423, miR-330-3p, miR-145, piR-651, and MALAT1 can be considered as potential biomarkers of LCBM.

Keywords: Biomarker; Brain metastasis; LncRNA; Lung cancer; MiRNA; Non-coding RNA.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / secondary
  • Gene Expression Regulation, Neoplastic
  • Genetic Variation*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Predictive Value of Tests
  • Prognosis
  • RNA, Untranslated / genetics*
  • RNA, Untranslated / metabolism
  • Risk Assessment
  • Risk Factors
  • Signal Transduction

Substances

  • Biomarkers, Tumor
  • RNA, Untranslated