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Review
. 2022 Feb 24;14(5):1171.
doi: 10.3390/cancers14051171.

The Use of miRNAs in Predicting Response to Neoadjuvant Therapy in Oesophageal Cancer

Cameron C J Lang  1 , Megan Lloyd  1 , Said Alyacoubi  1 , Saqib Rahman  1 , Oliver Pickering  1 , Tim Underwood  1 , Stella P Breininger  1
Affiliations
Review

The Use of miRNAs in Predicting Response to Neoadjuvant Therapy in Oesophageal Cancer

Cameron C J Lang et al. Cancers (Basel). .

Abstract

Oesophageal cancer (OC) is the ninth most common cancer worldwide. Patients receive neoadjuvant therapy (NAT) as standard of care, but less than 20% of patients with oesophageal adenocarcinoma (OAC) or a third of oesophageal squamous cell carcinoma (OSCC) patients, obtain a clinically meaningful response. Developing a method of determining a patient's response to NAT before treatment will allow rational treatment decisions to be made, thus improving patient outcome and quality of life. (1) Background: To determine the use and accuracy of microRNAs as biomarkers of response to NAT in patients with OAC or OSCC. (2) Methods: MEDLINE, EMBASE, Web of Science and the Cochrane library were searched to identify studies investigating microRNAs in treatment naïve biopsies to predict response to NAT in OC patients. (3) Results: A panel of 20 microRNAs were identified as predictors of good or poor response to NAT, from 15 studies. Specifically, miR-99b, miR-451 and miR-505 showed the strongest ability to predict response in OAC patients along with miR-193b in OSCC patients. (4) Conclusions: MicroRNAs are valuable biomarkers of response to NAT in OC. Research is needed to understand the effects different types of chemotherapy and chemoradiotherapy have on the predictive value of microRNAs; studies also require greater standardization in how response is defined.

Keywords: chemoradiotherapy; chemotherapy; microRNAs; neoadjuvant therapy; oesophageal adenocarcinoma; oesophageal squamous cell carcinoma; predicting response.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Current treatment strategies for oesophageal cancer as outlined by the European Society of Medical Oncology. TNM staging: T describes tumour size and any cancer spread into adjacent tissue; N describes cancer spread to adjacent lymph nodes; M describes metastasis (Adapted from “Oesophageal Cancer: ESMO clinical Practice Guidelines” (2016) [27]. Created with BioRender.com, accessed on 17 February 2022).
Figure 2
Figure 2
Synthesis and action of miRNA in post-transcriptional gene regulation. Transcription of miRNA gene via RNA Polymerase II forms pri-miRNA, DROSHA (class 2 ribonuclease III enzyme) and DGCR8 cleave the terminal end of the miRNA hairpin to form pre-miRNA. This is exported via RAN and XPO1/5. The miRNA hairpin is then cleaved by Dicer. AGO-2 binds to the double stranded miRNA, unwinds and dissociates the strands then forms a complex with RISC. This leads to either miRNA degradation or inhibition of ribosome binding. Abbreviations: pri-miRNA: primary-miRNA, pre-miRNA: precursor-miRNA, DGCR8: DiGeorge syndrome critical region gene 8, XPO 1/5: Exportin 1/5, RISC: RNA-induced silencing complex. (Created with BioRender.com, accessed on 16 January2022).
Figure 3
Figure 3
Schematic illustration of review articles included in this manuscript.
Figure 4
Figure 4
Overview of results produced by all 15 discussed articles. The NAT regimen utilised and how this relates to pre-treatment expression profiles in responders to nChemo or nCRT is shown. Abbreviations: OSCC; Oesophageal Squamous Cell Carcinoma, OAC; Oesophageal Adenocarcinoma, nChemo; Neopadjuvant chemotherapy, nCRT; Neoadjuvant Chemoradiotherapy. (Created with BioRender.com, accessed on 17 February 2022).
See this image and copyright information in PMC

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