TEP linc-GTF2H2-1, RP3-466P17.2, and lnc-ST8SIA4-12 as novel biomarkers for lung cancer diagnosis and progression prediction.

Abstract

Platelets contain a rich repertoire of RNA species, such as mRNAs and long non-coding RNAs. During the development of tumors, platelets are "educated" by cancer cells, altering their transcriptome and molecular content, thereby, tumor educated platelet (TEP) lncRNA profile has the potential to diagnose lung cancer. The current study was aimed to examine whether TEPs might be a potential biomarker for lung cancer. Platelet precipitation was obtained by low-speed centrifugation. TEP linc-GTF2H2-1, RP3-466P17.2, and lnc-ST8SIA4-12 were selected by lncRNA microarray and validated by qPCR in a large cohort of lung cancer patients and healthy donors. Besides, we analyzed the association of their expression levels with clinicopathological features. TEP linc-GTF2H2-1 and RP3-466P17.2 were significantly downregulated, while lnc-ST8SIA4-12 was significantly upregulated in patients with lung cancer or with early-stage lung cancer as compared to healthy donors, possessing AUCs of 0.781, 0.788, 0.725 for lung cancer and 0.704, 0.771, 0.768 for early-stage lung cancer, respectively. Notably, their combination demonstrated the markedly elevated AUCs of 0.921 for lung cancer and 0.895 for early-stage lung cancer. Besides, the combination of TEP linc-GTF2H2-1 was capable to facilitate diagnostic efficiencies of CEA, Cyfra21-1, or NSE to distinguish advanced-stage lung cancer patients from early ones, with an AUC of 0.899 based on the integration of these four factors. Our data suggested that lncRNAs sequestered in TEPs enabled blood-based lung cancer diagnosis and progression prediction.