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REG4 is an indicator for KRAS mutant lung adenocarcinoma with TTF-1 low expression

Si Sun1,2, Zhihuang Hu1,2, Shenglin Huang3

  • 1Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, China.

Journal of Cancer Research and Clinical Oncology
|August 21, 2019
PubMed
Abstract

Insights

Researchers identified REG4 as a key biomarker in KRAS-driven lung adenocarcinoma, particularly the KC subtype. Silencing REG4 reduced tumor growth, suggesting its therapeutic potential.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Lung adenocarcinoma (LUAD) with KRAS mutation is classified into KP, KL, and KC subtypes based on co-occurring genetic events.
  • The KC subtype is characterized by CDKN2A/B inactivation and low TTF-1 expression.
  • Identifying specific molecular drivers is crucial for understanding LUAD pathogenesis, especially in the KC subtype.

Purpose of the Study:

  • To identify novel biomarkers contributing to lung adenocarcinoma pathogenesis.
  • To investigate the role of candidate molecules, particularly in the KC subtype of KRAS-mutant LUAD.

Main Methods:

  • Analysis of public datasets (E-GEOD-31210, TCGA) to identify candidate molecules.
  • Validation using quantitative real-time PCR in an independent cohort of 55 clinical samples.
  • Functional studies including in vitro and in vivo assays after REG4 silencing, coupled with RNA sequencing and Gene Set Enrichment Analysis (GSEA).

Main Results:

  • REG4, a regulator of gastrointestinal carcinogenesis, was found to be highly expressed in KRAS-mutant LUAD with low TTF-1 expression (KC subtype).
  • Gene expression analysis and immunohistochemistry confirmed high REG4 expression in an independent clinical cohort.
  • Silencing REG4 significantly reduced cancer cell proliferation and tumorigenesis, potentially by inducing cell cycle arrest via G2/M checkpoint and E2F targets.

Conclusions:

  • REG4 plays a significant role in the pathogenesis of KRAS-driven lung cancer.
  • REG4 is identified as a novel biomarker for a specific lung adenocarcinoma subtype.
  • Further research is warranted to elucidate REG4's mechanisms in KC tumor division and proliferation and its therapeutic potential.
Keywords:
KRASLung adenocarcinomaREG4SubtypeTTF-1

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