ACTN4 gene amplification is a predictive biomarker for adjuvant chemotherapy with UFT in stage I lung adenocarcinomas

This article was originally published here

Cancer Sci. 2021 Nov 29. doi: 10.1111/cas.15228. Online ahead of print.


Although adjuvant tegafur/uracil (UFT) is recommended for patients with completely resected stage I non-small cell lung cancer (NSCLC) in Japan, only one-third of cases has received adjuvant chemotherapy according to real-world data. Therefore, robust predictive biomarkers for selecting adjuvant chemotherapy (ADJ) or observation (OBS) without ADJ are needed. Patients who underwent complete resection of stage I lung adenocarcinoma with or without adjuvant UFT were enrolled. The status of ACTN4 gene amplification was analyzed by fluorescence in situ hybridization (FISH). Statistical analyses to determine whether the status of ACTN4 gene amplification affected recurrence-free survival (RFS) were performed. Formalin-fixed, paraffin-embedded (FFPE) samples from 1,136 lung adenocarcinomas were submitted for analysis of ACTN4 gene amplification. Ninety-nine (8.9%) of 1114 cases were positive for ACTN4 gene amplification. In the subgroup analysis of patients ≥ 65 years, the ADJ group had better RFS than the OBS group in the ACTN4-positive cohort (HR: 0.084, 95% CI: 0.009, 0.806; P = 0.032). The difference in RFS between the ADJ group and the OBS group was not significant in ACTN4-negative cases (all ages, HR: 1.214, 95% CI: 0.848, 1.738; P = 0.289). Analyses of ACTN4 gene amplification contributed to the decision regarding postoperative adjuvant chemotherapy for stage I lung adenocarcinomas, preventing recurrence, improving the quality of medical care, preventing the unnecessary side effects of adjuvant chemotherapy, and saving medical costs.

PMID:34845792 | DOI:10.1111/cas.15228