Dataset Information

Comprehensive analysis of circular RNA in oral leukoplakia: upregulated circHLA-C as a potential biomarker for diagnosis and prognosis.

ABSTRACT:

Background

Emerging evidence indicates that circular RNAs (circRNAs) play an indispensable role in a variety of tumors, yet the function of circRNAs in premalignant lesions is still obscure. Oral leukoplakia (OLK) is one of the most common premalignant lesions of the oral mucosa. Our study aimed to comprehensively investigate whether circRNAs contribute to the occurrence and development of OLK.

Methods

We obtained six pairs of OLK and normal oral mucosal (NOM) tissue samples and subjected them to high-throughput sequencing to detect the expression of circRNA. In total, 26 pairs of NOM and OLK tissues were used for validation. Key circRNAs were selected and further validated by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), ribonuclease (RNase) R digestion, and Sanger sequencing. Visualization analysis of circular human leukocyte antigen-C (circHLA-C) was performed in the UCSC Genome Browser (genome.ucsc.edu). Functional analysis of differentially expressed (DE) circRNAs were processed by Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Furthermore, TargetScan (www.targetscan.org) was applied to predict targeted micro RNAs (miRNAs) and messenger RNAs (mRNAs) of circRNAs and a competing endogenous RNA (ceRNA) network related with identified circRNAs was constructed in Cytoscape (v2.8.0).

Results

Profile data showed that 366 circRNAs were significantly altered in OLK tissues, including 65 upregulated and 301 downregulated circRNA transcripts. Compared with sequencing results, seven selected circRNAs expressed the same changing tendency. The amplest upregulated circRNA in our sequencing data, circHLA-C, was confirmed through back-splice junction sequences by Sanger sequencing after RNase R digestion. Correlation analysis demonstrated that circHLA-C correlated positively with the degree of dysplasia. Furthermore, receiver operating characteristic (ROC) curve analysis indicated that circHLA-C had potential diagnostic value with excellent accuracy and specificity.

Conclusions

According to the literature, we were the first to uncover the expression profiles of circRNAs in OLK. Our research performed a comprehensive bioinformatics analysis of DE circRNAs in OLK and identified circHLA-C as a promising diagnostic biomarker with potential as a therapeutic genetic target for OLK.

SUBMITTER: Xu S

PROVIDER: S-EPMC7723659 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

Comprehensive analysis of circular RNA in oral leukoplakia: upregulated circHLA-C as a potential biomarker for diagnosis and prognosis.

Xu Siming S Song Yuhan Y Shao Yanxiong Y Zhou Haiwen H

Annals of translational medicine 20201101 21

<h4>Background</h4>Emerging evidence indicates that circular RNAs (circRNAs) play an indispensable role in a variety of tumors, yet the function of circRNAs in premalignant lesions is still obscure. Oral leukoplakia (OLK) is one of the most common premalignant lesions of the oral mucosa. Our study aimed to comprehensively investigate whether circRNAs contribute to the occurrence and development of OLK.<h4>Methods</h4>We obtained six pairs of OLK and normal oral mucosal (NOM) tissue samples and s ...[more]

PMID: 33313120

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Project description:PurposeThe morbidity and mortality of gastric cancer (GC) remain high worldwide. In recent years, circular RNAs (circRNAs) have attracted widespread attention among cancer researchers due to the stable ring structure. The present work aims to find serum circRNA biomarkers that can be used in clinical applications and effective diagnosis.MethodsHsa_circ_0007507 was extracted through circRNA sequencing. Exonuclease digestion assay, actinomycin D, agarose gel electrophoresis (AGE), and Sanger sequencing verified the potential of hsa_circ_0007507 as a biomarker. Besides, a real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was established to detect the level of expression of hsa_circ_0007507. Twenty cases of GC and the paired adjacent tissues were collected to verify its overexpression. Then, serum samples from 30 cases of colorectal cancer, 30 cases of thyroid cancer, and 30 cases of breast cancer were collected to verify their organ specificity. Additionally, serum samples from 80 healthy people, 62 gastritis patients, 31 intestinal metaplasia patients, and 100 GC patients were collected, and the diagnostic efficacy was evaluated through analysis of the receiver operating characteristic (ROC) curve. Furthermore, 16 post-operative GC samples, samples of 65 relapsed patients and 36 non-relapsed patients were collected to evaluate the prognosis of GC.ResultsThe level of expression of hsa_circ_0007507 in GC tissues was up-regulated (p = 0.0121), which was consistent with the results of circRNA sequencing. Exonuclease digestion assay and actinomycin D confirmed that hsa_circ_0007507 had a stable structure and a longer half-life. In the analysis of organ specificity experiments, serum hsa_circ_0007507 did not have specificity for patients with colorectal cancer (p = 0.5319), thyroid cancer (p = 0.5422), or breast cancer (p = 0.5178). Analysis of diagnostic efficacy indicated that the expression of hsa_circ_0007507 was significantly higher than that of normal people (p <0.0001); the area under the ROC (AUC) was 0.832 (95% CI: 0.771-0.892); the diagnostic power of hsa_circ_0007507 was higher than that of CEA (AUC = 0.765, 95% CI: 0.697-0.833) and CA199 (AUC = 0.587, 95% CI: 0.504-0.67). Through diagnosis using a combination of the three, GC patients could be distinguished from normal people (AUC = 0.849), and higher diagnostic efficiency could be achieved. The expression of serum hsa_circ_0007507 in GC patients significantly decreased after surgery (p = 0.001). Besides, the expression of serum hsa_circ_0007507 in patients with post-operative recurrence was significantly up-regulated again (p = 0.0139).ConclusionsSerum hsa_circ_0007507 is differentially expressed in GC patients, post-operative GC patients, gastritis patients, intestinal metaplasia patients and relapsed patients, suggesting that serum hsa_circ_0007507 can be used as a new diagnostic and dynamic monitoring biomarker for GC.

Dataset Information

Comprehensive analysis of circular RNA in oral leukoplakia: upregulated circHLA-C as a potential biomarker for diagnosis and prognosis.

Background

Methods

Results

Conclusions

Publications

Comprehensive analysis of circular RNA in oral leukoplakia: upregulated circHLA-C as a potential biomarker for diagnosis and prognosis.

Similar Datasets

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