Gene amplification of ACTN4 is a predictive biomarker for the adjuvant chemotherapy with Uracil-Tegaful in stage-I patients with adenocarcinoma of the lung.

Author(s)：

Rintaro Noro¹, Kazufumi Honda^8,9, Kengo Nagashima³, Noriko Motoi², Shinobu Kunugi⁴, Jun Matsubayashi⁵,
Susumu Takeuchi⁶, Hideaki Shiraishi⁹, Tetsuya Okano⁶, Jitsuo Usuda⁶, Shunichi Watanabe⁷, Norihiko Ikeda⁶, Masahiro Seike¹,
Akihiko Gemma¹, Kaoru Kubota¹

Affiliation(s)：

¹Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, School of Medicine, Nippon Medical School, ²Pathology & Clinical Laboratory Division, National Cancer Center Hospital,³The Institute of Statistical Mathematics,, Research Center for Medical and Health Data Science,⁴Department of Analytic Human Pathology, Graduate School of Medicine, Graduate School, Nippon Medical School,⁵Department of Anatomical Pathology, Hospital, Tokyo Medical University,⁶Department of Thoracic Surgery, Hospital, Tokyo Medical University,⁷Department of Thoracic Surgery, National Cancer Center Hospital,⁸.Department of Bioregulation, Graduate School of Medicine, Graduate School, Nippon Medical School,⁹Department of Biomarkers for Early Detection of Cancer, National Cancer Center Research Institute

Introduction: Although the adjuvant tegafur/uracil (UFT) chemotherapy is recommended for patients with completely resected patients with stage I non-small cell lung cancer (NSCLC) in Japan, only one-third received adjuvant chemotherapy according to real-world data. Therefore the robust predictive biomarkers for selecting adjuvant chemotherapy (ADJ) or observation (OBS) without ADJ, would be needed.
Methods: The patients who underwent the adjuvant with UFT administration or observation after complete resection of stage I lung adenocarcinoma, were enrolled in this study. The status of ACTN4 gene amplification analyzed by Fluorescence in situ hybridization (FISH). The statistical analyses whether the status of ACTN4 gene amplification affected the progression free survival (RFS), has been performed.
Results: The formalin-fixed paraffin-embedded (FFPE) samples from 1136 lung adenocarcinomas were submitted to analyze of ACTN4 gene amplification. Ninety-nine (8.9%) and 1015 (91.1%) of 1114 cases had positive and negative of ACTN4 gene amplification, respectively. The RFS of ADJ group tended to be better than one of OBS group in ACTN4 positive cases (HR: 0.686, 95%CI: 0.234, 2.012, p=0.492, N = 97). In the subgroup analysis of ≧65 years, ADJ group had significant better RFS than OBS group in ACTN4 positive cohort (HR: 0.084, 95%CI: 0.009, 0.806, p=0.032, N = 64 ). On the other hand, the significant difference recognized between ADJ group and OBS group in all cohort and the subgroup of ≧65 years, respectively (HR: 1.162, 95%CI: 0.835, 1.618; p= 0.373, N = 1086, HR: 0.923; 95% CI0.566, 1.506; p= 0.748, N=649)
Conclusion: The analyses of ACTN4 gene amplification in clinical setting, contributed to the decision of postoperative adjuvant chemotherapy with stage I lung adenocarcinomas, preventing the recurrence, improving the quality of medical care, prevent the useless side effect by adjuvant chemotherapy, and saving the medical costs.