Clinical significance of BIM deletion polymorphism in chemoradiotherapy for non-small cell lung cancer.
Yu WakabayashiTakeshi MasudaKazunori FujitakaTaku NakashimaJoe OkumotoKiyofumi ShimojiYoshifumi NishimuraKakuhiro YamaguchiShinjiro SakamotoYasushi HorimasuShintaro MiyamotoHiroshi IwamotoShinichiro OhshimoHironobu HamadaNoboru HattoriPublished in: Cancer science (2020)
The standard treatment for locally advanced non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) followed by anti-programmed cell death-ligand 1 (anti-PD-L1) treatment. BIM deletion polymorphism induces the suppression of apoptosis resulting from epidermal growth factor (EGFR)-tyrosine kinase inhibitors in EGFR-mutated NSCLC patients. We aimed to examine the effects of BIM polymorphism on CRT and anti-PD-L1/PD-1 treatment in NSCLC patients. In this retrospective study of 1312 patients with unresectable NSCLC treated at Higashi-Hiroshima Medical Center and Hiroshima University Hospital between April 1994 and October 2019, we enrolled those who underwent CRT or chemotherapy using carboplatin + paclitaxel or cisplatin + vinorelbine, or anti-PD-L1/PD-1 treatment. Of 1312 patients, 88, 80, and 74 underwent CRT, chemotherapy, and anti-PD-L1/PD-1 treatment, respectively, and 17.0%, 15.2% and 17.6% of these patients showed BIM polymorphism. Among patients receiving CRT, the progression-free survival was significantly shorter in those with BIM deletion than in those without. In the multivariate analyses, BIM polymorphism was an independent factor of poor anti-tumor effects. These results were not observed in the chemotherapy and anti-PD-L1/PD-1 treatment groups. In in vitro experiments, BIM expression suppression using small interfering RNA in NSCLC cell lines showed a significantly suppressed anti-tumor effect and apoptosis after irradiation but not chemotherapy. In conclusion, we showed that BIM polymorphism was a poor-predictive factor for anti-tumor effects in NSCLC patients who underwent CRT, specifically radiotherapy. In the implementation of CRT in patients with BIM polymorphism, we should consider subsequent treatment, keeping in mind that CRT may be insufficient.
Keyphrases
- small cell lung cancer
- advanced non small cell lung cancer
- end stage renal disease
- ejection fraction
- newly diagnosed
- locally advanced
- growth factor
- epidermal growth factor receptor
- oxidative stress
- cardiac resynchronization therapy
- healthcare
- prognostic factors
- heart failure
- clinical trial
- poor prognosis
- signaling pathway
- cell proliferation
- long non coding rna
- replacement therapy
- phase ii study
- binding protein