Peran Mutasi KRAS dan TP53 sebagai Faktor Prognostik Kanker Paru

Abstract

Background: Currently, the development of lung cancer therapy has entered the era of targeted therapy based on its molecular profile, where smoking-associated malignancies show a varied and interrelated genomic mutation profile. KRAS mutations and TP53 mutations are mutations that occur in smoking-related lung cancer and affect the low rate of therapeutic success and survival of lung cancer patients. This study aims to assess the role of KRAS and TP53 mutations as prognostic factors for lung cancer Methods: This study is a retrospective cohort study conducted in 2020-2021 and involved 107 subjects with certain inclusion and exclusion criteria. However, only 52 paraffin blocks from bronchoscopy, Trans Thoracal Lung Biopsy (TTLB), and open surgery procedures were successfully extracted using the FFPE Quick-DNA mini preparation. KRAS gene and TP53 gene were amplified using PCR with specific primers for exon 2 (KRAS) and exon 5- 9 (TP53). Sequencing analysis was performed using Unipro Ugene software and compared with reference sequences. Protein base changes were then analyzed by BLASTn application. All clinical characteristics were obtained from medical records. The patient's prognosis was assessed for overall survival (OS) and progression free survival (PFS) by survival analysis with Kaplan Meier and Logrank analysis to assess the associations between OS and PFS with TP53 and KRAS mutations. Results: The majority of the subjects were men with the age of more than 60 years, heavy smokers, with adenocarcinoma lung cancer. KRAS mutations were not detected in all study subjects. TP53 mutations were detected in 5 subjects at exons 5, 6, and 8. During the analysis, it was seen that the median OS of patients with TP53 mutations was 7 months while those without mutations was 9 months. Meanwhile, the median PFS of patients with TP53 mutations was 3 months while those without mutations was 6 months. In statistical tests, there is no associations between TP53 mutations and OS and PFS of lung cancer patients with p-value > 0.05 Conclusion: TP53 and KRAS mutations do not have a significant effect on the prognosis of lung cancer patients.