RNF128 expression in lung adenocarcinoma is a favorable prognostic factor associated with decreased tumor-associated macrophages.

Objectives: Molecular-level research has linked RING finger (RNF) protein family members to carcinogenesis and tumor progression. Among them, RNF128 is related to tumor progression, but reports on its association with lung cancer are few. This study aimed to clarify the unknown association between RNF128 expression and clinical outcomes in patients with lung adenocarcinoma.

Methods: Clinical data of 545 patients with therapy-naïve lung adenocarcinoma who underwent lobectomy with systematic lymph node dissection between 1999 and 2016 were retrospectively reviewed. Histological and immunohistochemical analyses were conducted to evaluate the relationship between RNF128 expression and prognosis.

Results: Among adenocarcinoma histologic types, acinar, micropapillary, and solid tumors did not express RNF128 compared with other histologic types (p < 0.001). Patients with high RNF128 expression exhibited fewer clusters of differentiated (CD) 68+ tumor-associated macrophages (TAMs) and CD163+ TAMs. Multivariate analysis of relapse-free survival (RFS) and overall survival (OS) revealed that the lack of RNF128 expression was an independent prognostic factor for poor RFS (hazard ratio [HR] 1.60, p = 0.029) and OS (HR 1.83, p = 0.041), suggesting that RNF128 expression is a favorable prognostic factor.

Conclusion: RNF128 expression may be an independent predictor of favorable outcomes in Japanese patients with untreated lung adenocarcinoma who undergo surgical resection. Further elucidation of the role of TAM-related E3 ubiquitin ligase in immune function may facilitate the development of effective immunomodulatory therapies for lung adenocarcinoma.