Abstract
The 2021 WHO classification proposed a pattern-based grading system for early-stage invasive non-mucinous lung adenocarcinoma. Lung adenocarcinomas with high-grade patterns have poorer outcomes than those with lepidic-predominant patterns. This study aimed to establish genetic prognostic signatures by comparing differences in gene expression profiles between low- and high-grade adenocarcinomas. Twenty-six (9 low- and 17 high-grade adenocarcinomas) patients with histologically “near-pure” patterns (predominant pattern comprising >70% of tumor areas) were selected retrospectively. Using RNA sequencing, gene expression profiles between the low- and high-grade groups were analyzed, and genes with significantly different expression levels between these two groups were selected for genetic prognostic signatures. In total, 196 significant candidate genes (164 upregulated and 32 upregulated in the high- and low-grade groups, respectively) were identified. After intersection with The Cancer Genome Atlas–Lung Adenocarcinoma prognostic genes, three genes, exonuclease 1 (EXO1), family with sequence similarity 83, member A (FAM83A), and disks large-associated protein 5 (DLGAP5), were identified as prognostic gene signatures. Two independent cohorts were used for validation, and the areas under the time-dependent receiver operating characteristic were 0.784 and 0.703 in the GSE31210 and GSE30219 cohorts, respectively. Our result showed the feasibility and accuracy of this novel three-gene prognostic signature for predicting the clinical outcomes of lung adenocarcinoma.
Highlights
The investigations were performed in a retrospective cohort of 26 individuals with surgically resected lung adenocarcinoma who were managed at the National Taiwan
Of the 26 patients included in the study cohort, 9 (34.6%) and 17 (65.4%) had low-grade subtype and high-grade subtype lung adenocarcinomas, respectively (Table 1)
Gene signatures for prognostic prediction based on gene expression profiles of patients with lung cancer have been reported in several previous studies
Summary
The International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society proposed a new classification system for lung adenocarcinoma in 2011 [1]. The new classification system divides lung adenocarcinoma into five subtypes (lepidic, acinar, papillary, micropapillary, and solid), and the effect of the new classification on the prediction of survival rate and recurrence has been reported [2,3]. Patients with micropapillary- and solid-predominant adenocarcinomas have a higher recurrence rate than patients with lepidic-predominant adenocarcinomas. Patients with early-stage lung adenocarcinoma with high-grade subtypes (solid and micropapillary) have higher recurrence rate and poorer prognosis than those with
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