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.
Highlights
As per the recent GLOBOCAN 2020 data, esophageal cancer (EC) is the eighth most common cancer and the sixth leading cause of death globally [1]
Our pilot study revealed 296 differentially expressed long non-coding RNAs (lncRNAs) in esophageal squamous cell carcinoma (ESCC) blood samples compared to healthy control individuals
Out of these 296 lncRNAs, LINC00324 and LOC100507053 were significantly up and downregulated respectively in ESCC patients compared to healthy individuals
Summary
As per the recent GLOBOCAN 2020 data, esophageal cancer (EC) is the eighth most common cancer and the sixth leading cause of death globally [1]. A hospital-based analysis of 2088 patients in Northern India revealed esophageal cancer as the fourth (10.39%) most prevalent cancer [2]. Because of the substantial increase in the incidence and mortality rates along with the decrease in the 5-year survival rate of EC (~18%), esophageal cancer has become a severe global public health challenge [3]. Based on EC histology, it is classified into adenocarcinoma (AC) and esophageal squamous cell carcinoma (ESCC). Our previous hospital-based study demonstrated 96.5% of esophagus tumors were squamous cell carcinoma, whereas 1.7% were adenocarcinoma [2]. It is imperative to identify blood-based minimally invasive agents, which can be used as potential diagnostic and prognostic markers for ESCC patients. Despite 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. Long non-coding RNAs (lncRNAs) have emerged as essential players in the diagnosis and prognosis of various cancers
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