The Potential Diagnostic Value of Exosomal Long Noncoding RNAs in Solid Tumors: A Meta-Analysis and Systematic Review

Abstract

Background: Exosomes are defined as small membranous vesicles. After RNA content was discovered in exosomes, they emerged as a novel approach for the treatment and diagnosis of cancer. Long noncoding RNAs (lncRNA), a kind of specific RNA transcript, have been reported to function as tumor growth, metastasis, invasion, and prognosis by regulating the tumor microenvironment in exosomes. This study aims at exploring the potential diagnostic of exosomal lncRNA in solid tumors.

Methods: A meta-analysis conducted from January 2000 to October 2019 identified publications in the English language. We searched all relevant English literature from the Web of Science, EMBASE, and PubMed databases through October 1, 2019. The articles were strictly screened by our criteria and critiqued using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Results: There were 28 studies with 19 articles (4017 patients) identified, including studies on gastric cancer, laryngeal squamous cell carcinoma, colorectal cancer, cholangiocarcinoma, breast cancer, esophageal squamous cell carcinoma, hepatocellular carcinoma, nonsmall cell lung cancer, and prostate cancer. A meta-analysis showed that the combined value of sensitivity in 29 studies was 0.74 (95% confidence interval [CI], 0.7-0.78), and the combined value of specificity in the studies was 0.81 (95% CI, 0.78-0.83). This suggests the high diagnostic efficacy of liquid exosomes in cancer patients. It is statistically insignificant in terms of sex, ethnicity, and year. The diagnostic power of urinary system tumors was found to be higher than that of digestive system tumors by several subgroup analyses.

Conclusions: We performed a meta-analysis and literature review of 28 studies that included 4017 patients with 10 malignant cancer types. Mechanistically, our study demonstrated that lncRNAs in exosomes could be a promising bioindicator for the diagnosis and prognosis of solid tumors. INPLASY Registration Number: INPLASY202060083.

Figure 1

Overall quality assessment of the included articles using the QUADAS-2 tool.

Figure 2

Forest plot of sensitivity and specificity for the diagnosis of lncRNA of liquid exosomes in tumor among 28 studies.

Figure 3

Forest plot of DLR+ and DLR- (DLR: degrees of freedom) for diagnosis of lncRNA of liquid exosomes in tumor among 28 studies.

Figure 4

Forest plot of DOR (DOR: diagnostic OR) for diagnosis of lncRNA of liquid exosomes in tumor among 28 studies.

Figure 5

The SROC of the liquid exosomes lncRNA for the diagnosis of cancer. (AUC: area under the curve; SROC: summary receiver operator characteristic).

Figure 6

Deek's funnel plot asymmetry test for assessing publication bias.

Figure 7

Fagan plot to show the clinical significance in the cancer diagnosis of lncRNA of liquid exosomes.

Figure 8

The dot plot of negative likelihood ratio to show the clinical significance in the cancer diagnosis of lncRNA of liquid exosomes.

Figure 9

The potential biological mechanisms of exosomal lncRNA. Exosomes can directly promote tumor growth, invasion, migration, and drug resistance. And indirectly promote tumor growth, invasion, migration by promoting angiogenesis, and regulate microenvironment.