Tumor-educated platelet RNA as a diagnostic biomarker for ground-glass opacity-related lung adenocarcinoma.

BACKGROUND

Ground-glass opacities (GGOs) are a common computed tomography (CT) imaging feature in various pulmonary diseases, including early-stage lung adenocarcinoma (LUAD). The investigation of tumor-specific biomarkers for the diagnosis of early LUAD holds significant clinical importance. The aim of this study was to integrate highly specific tumor-educated platelet (TEP)-derived biomarkers to optimize preoperative evaluation.

METHODS

After identifying differentially expressed genes (DEGs), six machine learning methods were applied to the sequencing results of cohort 1, generating a DEG-TEP data set. The DEGs in cohort 2 were considered to be the DEG-TISSUES data set. The intersection of these two gene sets was designated as the intersection-17 data set. Validation of the genes in intersection-17 was conducted in cohort 3 (tissues) and cohort 4 (platelets) via real-time reverse-transcription quantitative polymerase chain reaction (RT-qPCR). si- cell lines were established in PC9 and H1299 cell lines to validate the role of in LUAD . Finally, a single-gene gene set enrichment analysis (GSEA) was carried out for .

RESULTS

A total of 7,753 DEGs were identified in cohort 1. After machine learning was applied, the DEG-TEP data set, consisting of 108 DEGs, was established, while the DEG-TISSUES data set contained 1,909 genes. The RT-qPCR results in cohort 3 indicated that the messenger RNA expression of , , and in tissues was consistent with the sequencing results. In cohort 4, only exhibited differential expression, with an area under receiver operative characteristic curve of 0.78 (95% confidence interval: 0.61-0.95; P<0.01). We found that has a suppressive effect on the proliferation, invasion, and metastatic abilities of LUAD. The single-gene GSEA was applied to preliminarily characterize the biological functions of in tumors, revealing that is predominantly enriched in ribosome-related pathways.

CONCLUSIONS

We found that is significantly downregulated in tumor tissues and TEPs and that the low expression of promotes the proliferation, invasion, and metastatic abilities of tumor cells. We further discovered that had a low expression in the tissues and TEPs of patients with LUAD presenting as GGOs, and we further validated its diagnostic efficacy and tumor-suppressive effects. The downregulation in AHNAK may be associated with changes in the ribosomal pathway, affecting the malignancy of tumors.