Discovery of a novel linc01125 isoform in serum exosomes as a promising biomarker for NSCLC diagnosis and survival assessment.

Abstract

A non-invasive method to distinguish potential lung cancer patients would improve lung cancer prevention. We employed the RNA-sequencing analysis to profile serum exosomal long non-coding RNAs (lncRNAs) from non-small cell lung cancer (NSCLC) patients and pneumonia controls, and then determined the diagnostic and prognostic value of a promising lncRNA in four datasets. We identified 90 dysregulated lncRNAs for NSCLC and found the most significant lncRNA was a novel isoform of linc01125. Serum exosomal linc01125 could distinguish NSCLC cases from disease-free and tuberculosis controls, with the area under the curve values as 0.662 [95% confidence interval (CI) = 0.614-0.711] and 0.624 (95% CI = 0.522-0.725), respectively. High expression of exosomal linc01125 was also correlated with an unfavorable overall survival of NSCLC (hazard ratio = 1.48, 95% CI = 1.05-2.08). Clinic treatment decreased serum exosomal linc01125 in NSCLC patients (P = 0.036). Linc01125 functions to inhibit cancer growth and metastasis via acting as a competing endogenous RNA to up-regulate tumor necrosis factor alpha-induced protein 3 (TNFAIP3) expression by sponging miR-19b-3p. Notably, the oncogenic transformation of 16HBE led to decreased linc01125 in cells but increased linc01125 in cell-derived exosomes. The expression of linc01125 in total exosomes was highly correlated with that in tumor-associated exosomes in serum. Moreover, lung cancer cells were capable of releasing linc01125 into exosomes in vitro and in vivo. Our analyses suggest serum exosomal linc01125 as a promising biomarker for non-invasively diagnosing NSCLC and predicting the prognosis of NSCLC.

• Authors: Jianfeng Xian, Yuyuan Zeng, Shizhen Chen, Liming Lu, Li Liu, Jinbin Chen, Boqi Rao, Zhuxiang Zhao, Jun Liu, Chenli Xie, Lingling Zhu, Duo Zhang, Fuman Qiu, Jiachun Lu, Lei Yang
• Journal: Carcinogenesis (Carcinogenesis) Vol. 42 Issue 6 Pg. 831-841 (06 21 2021) ISSN: 1460-2180 [Electronic] England
• PMID: 33928340 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Biomarkers, Tumor
• Protein Isoforms
• RNA, Long Noncoding

Topics

• Biomarkers, Tumor (blood, genetics)
• Carcinoma, Non-Small-Cell Lung (blood, mortality, pathology, surgery)
• Case-Control Studies
• Exosomes (genetics)
• Female
• Follow-Up Studies
• Gene Expression Regulation, Neoplastic
• Humans
• Lung Neoplasms (blood, mortality, pathology, surgery)
• Male
• Prognosis
• Protein Isoforms
• RNA, Long Noncoding (blood, genetics)
• Survival Rate