Analysis of tumor cell proliferation (Ki-67) and cell cycle regulator proteins in lung adenocarcinoma with different radiological subtypes.

Background: The prognosis of ground glass opacity featured lung adenocarcinomas (GGO-LUAD) is significantly better than that of solid nodule featured lung adenocarcinomas (SN-LUAD), but the underlying reasons remain unclear. Ki-67 and cell cycle regulator proteins are highly expressed in many cancers and linked to prognosis. This study aims to investigate their differential expression in LUAD with different radiological subtypes.

Methods: Patients with resected pathological stage 0-III LUAD in our department between July 2019 and March 2022 were retrospectively reviewed. All included patients were divided into four groups based on different consolidation-to-tumour ratio (CTR), we focuses on evaluating the differential expression of Ki-67 and cell cycle regulatory proteins (CCNA2, CCNB1, CCND1, P16, P21, TOP2A, TP53, and pRb) in LUAD with different CTR.

Results: A total of 481 patients were included, 108 in the pure ground glass opacity (PGGO, CTR = 0) group, 103 in the GGO-dominant (GGO-D, 0 < CTR ≤ 0.5) group, 74 in the SN-dominant (SN-D, 0.5 < CTR < 1) group, and 196 in the pure solid nodule (SN, CTR = 1) group. The expression of Ki-67 was significantly higher in elderly patients (P < 0.05), former or current smokers (P < 0.0001), males (P < 0.05), poorly differentiated tumors (P < 0.0001), and tumors with spread through air spaces (STAS) (P < 0.0001), and advanced stage tumors (P < 0.0001). Regardless of age, gender, smoking status and epidermal growth factor receptor (EGFR) mutation status, GGO-LUAD demonstrated significantly lower expression of Ki-67 compared to SN-LUAD. The expression of Ki-67 and cell cycle regulatory proteins (except P21) were significantly lower in the PGGO, GGO-D, SN-D than in the SN group. However, there was no significant difference in the expression of Ki-67 and cell cycle regulatory proteins among the PGGO, GGO-D, and SN-D groups.

Conclusions: GGO-LUAD demonstrated significantly lower expression of Ki-67 and cell cycle regulatory proteins compared to SN-LUAD, which may explain the reasons behind the excellent prognosis of GGO-LUAD.