Circulating Long Non-Coding RNAs LINC00324 and LOC100507053 as Potential Liquid Biopsy Markers for Esophageal Squamous Cell Carcinoma: A Pilot Study

Abstract

BackgroundDespite the availability of advanced technology to detect and treat esophageal squamous cell carcinoma (ESCC), the 5-year survival rate of ESCC patients is still meager. Recently, long non-coding RNAs (lncRNAs) have emerged as essential players in the diagnosis and prognosis of various cancers.ObjectiveThis pilot study focused on identifying circulating lncRNAs as liquid biopsy markers for the ESCC.MethodologyWe performed next-generation sequencing (NGS) to profile circulating lncRNAs in ESCC and healthy individuals’ blood samples. The expression of the top five upregulated and top five downregulated lncRNAs were validated through quantitative real-time PCR (qRT-PCR), including samples used for the NGS. Later, we explored the diagnostic/prognostic potential of lncRNAs and their impact on the clinicopathological parameters of patients. To unravel the molecular target and pathways of identified lncRNAs, we utilized various bioinformatics tools such as lncRnome, RAID v2.0, Starbase, miRDB, TargetScan, Gene Ontology, and KEGG pathways.ResultsThrough NGS profiling, we obtained 159 upregulated, 137 downregulated, and 188 neutral lncRNAs in ESCC blood samples compared to healthy individuals. Among dysregulated lncRNAs, we observed LINC00324 significantly upregulated (2.11-fold; p-value = 0.0032) and LOC100507053 significantly downregulated (2.22-fold; p-value = 0.0001) in ESCC patients. Furthermore, we found LINC00324 and LOC100507053 could discriminate ESCC cancer patients’ from non-cancer individuals with higher accuracy of Area Under the ROC Curve (AUC) = 0.627 and 0.668, respectively. The Kaplan-Meier and log-rank analysis revealed higher expression levels of LINC00324 and lower expression levels of LOC100507053 well correlated with the poor prognosis of ESCC patients with a Hazard ratio of LINC00324 = 2.48 (95% CI: 1.055 to 5.835) and Hazard ratio of LOC100507053 = 4.75 (95% CI: 2.098 to 10.76)]. Moreover, we also observed lncRNAs expression well correlated with the age (>50 years), gender (Female), alcohol, tobacco, and hot beverages consumers. Using bioinformatics tools, we saw miR-493-5p as the direct molecular target of LINC00324 and interacted with the MAPK signaling pathway in ESCC pathogenesis.ConclusionThis pilot study suggests that circulating LINC00324 and LOC100507053 can be used as a liquid biopsy marker of ESCC; however, multicentric studies are still warranted.

Identification of mitophagy-related hub genes during the progression of spinal cord injury by integrated multinomial bioinformatics analysis

“…We predicted that lncRNA LINC00324 and small nucleolar RNA host gene 16 (SNHG16) regulate BAP1 and SKP1 through miRNAs. LINC00324 is an autophagy-related long non-coding RNA that can be used as a liquid biopsy marker for esophageal squamous cell carcinoma [ 56 ]. In patients with intervertebral disk degeneration (IDD), LINC00324 is upregulated and correlated with IDD development [ 57 ].…”

The crucial role of long non-coding RNAs in the pathogenesis, therapeutic response, and clinical implications of esophageal cancer

“…Nowadays, it is critical to develop non-invasive diagnostic methods to diagnose EC rather than invasive techniques. Besides, myriad published studies are addressing the circulating value of lncRNAs in ESCC as a potential non-invasive diagnostic biomarker for EC (105). The results of different reports summarize the diagnostic/prognostic value of lncRNAs in EC in Table 3.…”

Long Non-Coding RNAs: The New Frontier into Understanding the Etiology of Alcohol Use Disorder

“…This suggest that while in EA the most likely contributor of the association signal is coming from the ADH1B cluster, in the AA population, there are two independent association signals from the ADH1B cluster and LOC100507053 [63]. LOC100507053, an antisense lncRNA, is located in the same genomic region as ADH1B and therefore shares the same locus [73]. For reference, the spatial orientations of antisense lncRNAs are outlined in Figure 2.…”