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

Apr 14, 2025

Experts: Rirong Qu,Yang Zhang,Shenghui Qin,Jing Xiong,Xiangning Fu,Lequn Li,Dehao Tu,Yixin Cai

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.
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.
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.
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.

© 2025. The Author(s).

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ABOUT THE EXPERTS

Rirong Qu,Yang Zhang,Shenghui Qin,Jing Xiong,Xiangning Fu,Lequn Li,Dehao Tu,Yixin Cai

Rirong Qu

Thoracic Surgery Laboratory, Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jiefang Avenue, Wuhan, 430030, China.

Yang Zhang

Department of Pelvic Floor Rehabilitation, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Shenghui Qin

Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Jing Xiong

Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Xiangning Fu

Thoracic Surgery Laboratory, Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jiefang Avenue, Wuhan, 430030, China.

Lequn Li

Thoracic Surgery Laboratory, Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jiefang Avenue, Wuhan, 430030, China.

Dehao Tu

Department of Thoracic Surgery, Yueyang Central Hospital, Yueyang, 41400, Hunan, China. tudehao@hotmail.com.

Yixin Cai

Thoracic Surgery Laboratory, Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jiefang Avenue, Wuhan, 430030, China. caiyixin@tjh.tjmu.edu.cn.