Molecular Alterations in Lung Adenocarcinoma With Ground-Glass Nodules: A Systematic Review and Meta-Analysis

Zihan Wei; Ziyang Wang; Yuntao Nie; Kai Zhang; Haifeng Shen; Xin Wang; Manqi Wu; Fan Yang; Kezhong Chen

doi:10.3389/fonc.2021.724692

Molecular Alterations in Lung Adenocarcinoma With Ground-Glass Nodules: A Systematic Review and Meta-Analysis

Front Oncol. 2021 Sep 13:11:724692. doi: 10.3389/fonc.2021.724692. eCollection 2021.

Authors

Zihan Wei^{1

2}, Ziyang Wang^{1

2}, Yuntao Nie¹, Kai Zhang¹, Haifeng Shen¹, Xin Wang^{1

2}, Manqi Wu^{1

2}, Fan Yang¹, Kezhong Chen¹

Affiliations

¹ Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China.
² Health Science Center, Peking University, Beijing, China.

Abstract

Background and aims: Nodular ground-glass lesions have become increasingly common with the increased use of computed tomography (CT), while the genomic features of ground-glass opacities (GGOs) remain unclear. This study aims to comprehensively investigate the molecular alterations of GGOs and their correlation with radiological progression.

Methods: Studies from PubMed, Embase, Cochrane Library, and Web of Science, using PCR, targeted panel sequencing, whole exosome sequencing, and immunohistochemistry, and reporting genomic alterations or PD-L1 expressions in lung nodules presenting as GGOs until January 21, 2021 were included in this study. Chi-square test, random-effects model, and Z-test analysis were adopted to analyze the data.

Results: A total of 22 studies describing mutations in lung adenocarcinoma (LUAD) with GGOs were analyzed. EGFR was the most frequently mutative gene (51%, 95%CI 47%-56%), followed by TP53 (18%, 95%CI 6%-31%), HER2 (10%, 95%CI 0%-21%), ROS1 (6%, 95%CI 0%-18%), and KRAS (6%, 95%CI 3%-9%). The correlation between the frequency of EGFR mutation and radiological was observed and the differences were found to be not statistically significant in the subgroups, which are listed as below: radiological: gGGO 47.40%, 95%CI [38.48%; 56.40%]; sGGO 51.94%, 95%CI [45.15%; 58.69%]. The differences of the frequency of KRAS mutation in the different subgroups were also consistent with this conclusion, which are listed as: radiological gGGO 3.42, 95%CI [1.35%; 6.13%]; sGGO 12.27%, 95%CI [3.89%; 23.96%]. The pooled estimated rate of PD-L1 was 8.82%, 95%CI [5.20%-13.23%]. A total of 11.54% (3/26) of the SMGGNs were confirmed to be intrapulmonary spread by WES.

Conclusions: Somatic genetic alterations are considered in early-stage GGO patients without distinct changes of the frequency following the progress of the tumor. This review sheds insight on molecular alterations in LUAD with GGOs.

Keywords: EGFR; PD-L1; ground-glass-opacity; lung cancer; molecular alteration; systematic review.

Publication types

Systematic Review