Circulating Long Noncoding RNAs Act as Diagnostic Biomarkers in Non-Small Cell Lung Cancer

Abstract

Identification of novel effective early diagnostic biomarkers may provide alternative strategies to reduce the mortality for non-small cell lung cancer (NSCLC) patients. Circulating long non-coding RNAs (lncRNAs) have emerged as a new class of promising cancer biomarkers. Our study aimed to identify circulating lncRNAs for diagnosing NSCLC. A total 528 plasma samples were continuously collected and allocated to four progressive phases: discovery, training, verification, and expansion phases. The expression of candidate lung cancer related lncRNAs were detected using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). We identified a 4-lncRNA panel (RMRP, NEAT1, TUG1, and MALAT1) that provided a high diagnostic value in NSCLC (AUC = 0.86 and 0.89 for training and verification phase, respectively). Subgroup analyses showed that the 4-lncRNA panel had a sensitivity of 78.95% [95% confidence interval (CI) = 62.22%–89.86%] in stage I-II patients and 75.00% (95% CI = 52.95%–89.40%) in patients with small tumor size (≤3cm). Notably, the sensitivity of 4-lncRNA panel was significantly higher than that of routine protein panels in adenocarcinoma (CEA, CA125, and CYFRA21-1, 86.30% vs. 73.96%). Adding 4-lncRNA to protein markers significantly improved the diagnostic capacity in both adenocarcinoma (AUC=0.85, 95% CI = 0.78–0.91) and squamous cell carcinoma (AUC=0.93, 95% CI = 0.86–0.97). In conclusion, we identified a plasma 4-lncRNA panel that has considerable clinical value in diagnosing NSCLC. The 4-lncRNA panel could improve the diagnostic values of routine tumor protein markers in diagnosing NSCLC. Circulating lncRNAs could be used as promising candidates for NSCLC diagnosis.

LncRNA RNA Component of Mitochondrial RNA-Processing Endoribonuclease Promotes AKT-Dependent Breast Cancer Growth and Migration by Trapping MicroRNA-206

“…The oncogenic transcription factors, such as β-catenin, YAP, and c-MYC, can activate the transcription of RMRP ( Park and Jeong, 2015 ; Xiao et al, 2019 ) that promotes tumor cell survival and propagation by regulating the expression of, for example, Cyclin D2 and KRAS ( Meng et al, 2016 ; Shao et al, 2016 ). Importantly, the existence of RMRP in the blood plasma exhibits a diagnostic value for detection of lung cancer ( Leng et al, 2018 ; Yuan et al, 2020 ). However, the role of RMRP in breast cancer remains unclear.…”

The Effect of Genomic DNA Contamination on the Detection of Circulating Long Non-Coding RNAs: The Paradigm of MALAT1

“…NEAT1overexpression was associated with poor prognosis in several types of cancer, like breast [ 44 ] and digestive system tumors [ 9 ], and it was suggested that it could be used as a promising biomarker for diagnosis [ 45 ]. NORAD is another lncRNA, which is reported to be overexpressed in many cancers and several studies have explored its involvement in numerous processes associated with carcinogenesis [ 10 ].…”

Molecular Mechanisms and Functions of lncRNAs in the Inflammatory Reaction of Diabetes Mellitus

“…Increasing evidence shows that lncRNAs are involved in the development of common diseases. More importantly, lncRNAs are present in extracellular fluids (e.g., serum and urine) [ 94 ] and can be used as novel biomarkers for a variety of diseases, including diabetes [ 95 , 96 ]. Zhao et al [ 97 ] found that high expression of the lncRNA PANDAR is related to the development of DN in T2DM patients, and it may be a predictive biomarker of the prognosis of DN in patients.…”