Abstract: Background and purpose: Adenylate kinase 4 (AK4) is a key regulation enzyme that regulates the metabolism of adenylate and maintains homeostasis in vivo. Some studies show that AK4 promotes the invasion and metastasis of lung cancer cells and correlates with the poor prognosis of patients with lung carcinoma. However, the role of AK4 in the occurrence and development of early-stage lung adenocarcinoma is not clear. The purpose of this study was to investigate the change of AK4 expression in the carcinogenesis of early-stage lung adenocarcinoma and its relationship with clinicopathologic features, and to explore the role of AK4 in the carcinogenesis and progression of early-stage lung adenocarcinoma. Methods: Immunohistochemical EnVision method was used to detect the expression of AK4 in 297 cases of lung adenocarcinoma at different stages treated in Jiangdu People’s Hospital of Yangzhou from Jan. 2017 to Dec. 2019, including invasive adenocarcinoma (IA) (n=152), minimally invasive adenocarcinoma (MIA) (n=52), adenocarcinoma in situ (AIS) (n=60) and atypical adenomatous hyperplasia (AAH) (n=33), and normal tissues (n=30). Results: The expression rates of AK4 in AAH, AIS, MIA, and IA were 63.6%, 75.0%, 71.1%, and 81.6%, respectively, which were higher than in normal lung tissues, and the difference was statistically significant (P<0.01). However, there was no significant difference in expression of AK4 among AAH, AIS, MIA and IA (P>0.05). The expression rate of AK4 in lung adenocarcinoma with lymph node metastasis was higher compared with those without lymph node metastasis (P<0.05), and expression of AK4 was related to pTNM stage (P<0.05). However, expression of AK4 was related to gender, age, smoking status, tumor location and size, vascular invasion and pleura invasion (P>0.05). Conclusion: AK4 may be involved in not only early occurrence of lung adenocarcinoma, but also the progression of lung adenocarcinoma. AK4 may be a biomarker for the early diagnosis of lung adenocarcinoma and evaluation of disease progression.

Key words: Lung neoplasm, Adenocarcinoma, Adenylate Kinase, Clinical pathological features