**Dohun Kim 1, Yujin Kim 2, Bo Bin Lee 2, Dongho Kim 2, Ok-Jun Lee 3, Pildu Jeong 4, Wun-Jae Kim 4, Eun Yoon Cho 5, Joungho Han 5, Young Mog Shim <sup>6</sup> and Duk-Hwan Kim 2,\***


Received: 3 September 2020; Accepted: 21 September 2020; Published: 23 September 2020

**Abstract:** This study aimed to understand whether the effect of non-metastatic cells 1 (NME1) on recurrence-free survival (RFS) in early stage non-small cell lung cancer (NSCLC) can be modified by β-catenin overexpression and cisplatin-based adjuvant chemotherapy. Expression levels of NME1 and β-catenin were analyzed using immunohistochemistry in formalin-fixed paraffin-embedded tissues from 425 early stage NSCLC patients. Reduced NME1 expression was found in 39% of samples. The median duration of follow-up was 56 months, and recurrence was found in 186 (44%) of 425 patients. The negative effect of reduced NME1 expression on RFS was worsened by cisplatin-based adjuvant chemotherapy (adjusted hazard ratio = 3.26, 95% CI = 1.16–9.17, *p* = 0.03). β-catenin overexpression exacerbated the effect of reduced NME1 expression on RFS and the negative effect was greater when receiving cisplatin-based adjuvant chemotherapy: among patients treated with cisplatin-based adjuvant chemotherapy, hazard ratios of patients with reduced NME1 expression increased from 5.59 (95% confidence interval (CI) = 0.62–50.91, *p* = 0.13) to 15.52 (95% CI = 2.94–82.38, *p* = 0.001) by β-catenin overexpression, after adjusting for confounding factors. In conclusion, the present study suggests that cisplatin-based adjuvant chemotherapy needs to be carefully applied to early stage NSCLC patients with overexpressed β-catenin in combination with reduced NME1 expression.

**Keywords:** adjuvant chemotherapy; β-catenin; lung neoplasms; nucleotide-diphosphate kinase; recurrence
