Clinical Investigation of Chemotherapeutic Resistance and miRNA Expressions in Head and Neck Cancers: A Thorough PRISMA Compliant Systematic Review and Comprehensive Meta-Analysis

Abstract

Chemoresistance is a significant barrier to combating head and neck cancer, and decoding this resistance can widen the therapeutic application of such chemotherapeutic drugs. This systematic review and meta-analysis explores the influence of microRNA (miRNA) expressions on chemoresistance in head and neck cancers (HNC). The objective is to evaluate the theragnostic effects of microRNA expressions on chemoresistance in HNC patients and investigate the utility of miRNAs as biomarkers and avenues for new therapeutic targets. Methods: We performed a comprehensive bibliographic search that included the SCOPUS, PubMed, and Science Direct bibliographic databases. These searches conformed to a predefined set of search strategies. Following the PRISMA guidelines, inclusion and exclusion criteria were framed upon completing the literature search. The data items extracted were tabulated and collated in MS Excel. This spreadsheet was used to determine the effect size estimation for the theragnostic effects of miRNA expressions on chemoresistance in HNC, the hazard ratio (HR), and 95% confidence intervals (95% CI). The comprehensive meta-analysis was performed using the random effects model. Heterogeneity among the data collected was assessed using the Q test, Tau2, I2, and Z measures. Publication bias of the included studies was checked using the Egger’s bias indicator test, Orwin and classic fail-safe N test, Begg and Mazumdar rank collection test, and Duval and Tweedie’s trim and fill methods. Results: After collating the data from 23 studies, dysregulation of 34 miRNAs was observed in 2189 people. These data were gathered from 23 studies. Out of the 34 miRNAs considered, 22 were up-regulated, while 12 were down-regulated. The TaqMan transcription kits were the most used miRNA profiling platform, and miR-200c was seen to have a mixed dysregulation. We measured the overall pooled effect estimate of HR to be 1.516 for the various analyzed miRNA at a 95% confidence interval of 1.303–1.765, with a significant p-value. The null hypothesis test’s Z value was 5.377, and the p-value was correspondingly noted to be less than 0.0001. This outcome indicates that the risk of death is determined to be higher in up-regulated groups than in down-regulated groups. Among the 34 miRNAs that were investigated, seven miRNAs were associated with an improved prognosis, especially with the overexpression of these seven miRNAs (miR15b-5p, miR-548b, miR-519d, miR-1278, miR-145, miR-200c, Hsa- miR139-3p). Discussion: The findings reveal that intricate relationships between miRNAs’ expression and chemotherapeutic resistance in HNC are more likely to exist and can be potential therapeutic targets. This review suggests the involvement of specific miRNAs as predictors of chemoresistance and sensitivity in HNC. The examination of the current study results illustrates the significance of miRNA expression as a theragnostic biomarker in medical oncology.

Differential Expression of MicroRNA MiR-145 and MiR-155 Downstream Targets in Oral Cancers Exhibiting Limited Chemotherapy Resistance

“…These results confirmed the upregulation of miR-145 among this chemosensitive cell line previously reported by this group [47]. This supports other research that demonstrates that the downregulation of miR-145 expression was associated with oral cancer diagnosis and progression, while miR-145 upregulation correlated with improved prognosis and increased survival [31,39].…”

“…More specifically, systematic reviews and meta-analyses have established microRNA expression profiles for oral cancers including miR-21, miR-31, miR-155, and miR-196 [35][36][37][38]. In addition, many studies have revealed that microRNA expression also functions to mediate chemotherapy resistance among oral cancers [24,39]. For example, increased tumor resistance to Cisplatin has been linked with the upregulation of miR-21, but resistance among oral cancer has also been linked with miR-24, miR-218, and miR-629 upregulation, while miR-15b, miR-27b, and miR-155 upregulation may be associated with decreased resistance to Cisplatin within these same tumors [40][41][42][43][44][45].…”

Downstream Target Analysis for miR-365 among Oral Squamous Cell Carcinomas Reveals Differential Associations with Chemoresistance

“…However, this treatment may also be combined with radiation or chemotherapy to eliminate other potential cancerous cells that may not have been removed through surgical resection [ 9 , 10 ]. New evidence suggests that radiation and chemotherapy resistance are growing concerns within the field of oral oncology treatment, and more research is focused on determining the mechanisms that mediate these phenomena [ 11 , 12 ].…”