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Poor response to platinum-based chemotherapy is associated with KRAS mutation and concomitant low expression of BRAC1

Hongxuan Zhou1, Yun Dai2, Liqun Zhu3

  • 1Department of Oncology, Liyang People's Hospital, Liyang, Jiangsu, China.

The Journal of International Medical Research
|January 8, 2016
PubMed
Abstract

Insights

KRAS mutations in non-small cell lung cancer (NSCLC) patients correlate with shorter survival. Lower BRCA1 and TYMS expression was observed in KRAS-mutated tumors, with BRCA1 expression predicting outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality.
  • Platinum-based doublet chemotherapy is a standard treatment for NSCLC.
  • Identifying predictive biomarkers is crucial for optimizing NSCLC treatment strategies.

Purpose of the Study:

  • To investigate the prognostic value of KRAS mutation status in NSCLC patients treated with platinum-based chemotherapy.
  • To assess the association between tumor expression levels of BRCA1, TYMS, and SRC and treatment outcomes.
  • To explore the relationship between KRAS mutation status and the expression of these genes.

Main Methods:

  • Retrospective analysis of a cohort of NSCLC patients.
  • KRAS mutation status determined by amplification refractory mutation and quantitative polymerase chain reaction (PCR).
  • Tumor expression levels of BRCA1, TYMS, and SRC quantified using real-time quantitative PCR.

Main Results:

  • Patients with KRAS mutations exhibited significantly shorter survival compared to those with wild-type KRAS.
  • Tumor expression of BRCA1 and TYMS was significantly lower in patients with KRAS mutations.
  • Tumor expression of BRCA1 showed a positive correlation with survival duration, while SRC expression did not.
  • SRC expression levels did not differ significantly between patients with and without KRAS mutations.

Conclusions:

  • KRAS mutation status is a potential predictive biomarker for survival in NSCLC patients.
  • Tumor BRCA1 expression is a promising biomarker for predicting clinical outcomes in NSCLC.
  • Combined assessment of KRAS status and BRCA1 expression may aid in tailoring chemotherapy regimens for NSCLC.
Keywords:
BCA1KRASNonsmall cell lung cancer (NSCLC)TYMSdrug responseoverall survivalplatinum doublets

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