Case Control Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Mar 16, 2021; 9(8): 1785-1792
Published online Mar 16, 2021. doi: 10.12998/wjcc.v9.i8.1785
Association between homeobox protein transcript antisense intergenic ribonucleic acid genetic polymorphisms and cholangiocarcinoma
Dimitra Ioanna Lampropoulou, Konstantinos Laschos, Gerasimos Aravantinos, Konstantinos Georgiou, Konstantinos Papiris, George Theodoropoulos, Maria Gazouli, Dimitrios Filippou
Dimitra Ioanna Lampropoulou, Konstantinos Laschos, Gerasimos Aravantinos, Medical Oncology, General Oncology Hospital of Kifissia “Agioi Anargiroi”, Athens 14564, Greece
Konstantinos Georgiou, George Theodoropoulos, 1st Department of Propaedeutic Surgery, Hippokration General Hospital of Athens, Athens Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
Konstantinos Papiris, Endoscopic Surgery Department, Hippokration General Hospital, Athens 11527, Greece
Maria Gazouli, Basic Medical Sciences, Athens Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
Dimitrios Filippou, Anatomy and Surgical Anatomy, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
Author contributions: Lampropoulou DI and Laschos K performed the majority of the writing and were involved in the execution of the experiments; Gazouli M conceived the study, performed the majority of experiments, made critical revisions and writing; Papiris K, Aravantinos G, Georgiou K, Theodoropoulos G participated in the collection of the human samples and provided substantial contributions to the conception and design of the study; Filippou D made critical revisions and provided approval of the final version of the manuscript to be published.
Supported by The Hellenic Society of Medical Oncology, No. 8021/25.09.2020.
Institutional review board statement: The study was reviewed and approved by the Ippokrateion General Hospital Institutional Review Board (8798/12-6-2020).
Informed consent statement: All patients gave informed consent.
Conflict-of-interest statement: No conflict of interest to declare.
Data sharing statement: Not applicable.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Dimitrios Filippou, MD, PhD, Assistant Professor, Anatomy and Surgical Anatomy, Medical School, National and Kapodistrian University of Athens, M Asias 75 Gousi, Athens 11527, Greece. d_filippou@hotmail.com
Received: December 16, 2020
Peer-review started: December 16, 2020
First decision: December 31, 2020
Revised: January 4, 2021
Accepted: February 12, 2021
Article in press: February 12, 2021
Published online: March 16, 2021
Abstract
BACKGROUND

Cholangiocarcinoma (CCA) represents a rare but highly aggressive malignancy that is often challenging to diagnose, especially in early stages. The role of existing tumor biomarkers for CCA diagnosis, remains controversial due to their low sensitivity and specificity. Increasing evidence has implicated long non-coding ribonucleic acid polymorphisms with cancer susceptibility in a variety of tumor types. The association between long non-coding ribonucleic acid homeobox protein transcript antisense intergenic ribonucleic acid (HOTAIR) polymorphisms and CCA risk has not been reported yet.

AIM

To investigate the influence of HOTAIR variants on the risk of CCA development.

METHODS

We conducted a case-control study in which three HOTAIR single nucleotide polymorphisms (rs920778, rs4759314 and rs7958904) were genotyped in a Greek cohort. Our study population included 122 CCA patients (80 males and 42 females) and 165 healthy controls. The polymorphisms under investigation were examined in peripheral blood samples.

RESULTS

HOTAIR rs4759314 AG and GG genotypes were associated with a significantly increased CCA risk [P = 0.004, odds ratio: 3.13; 95% confidence interval: 1.65-5.91 and P = 0.005, odds ratio: 12.31; 95% confidence interval: 1.48-101.87, respectively]. However, no significant associations of HOTAIR rs920778, and rs7958904 were detected. Similarly, we found no significant associations between rs4759314 AA genotype and CCA susceptibility.

CONCLUSION

HOTAIR rs4759314 AG and GG genotypes may be implicated with CCA development and may serve as a potential diagnostic biomarker.

Keywords: Cholangiocarcinoma, Homeobox protein transcript antisense intergenic ribonucleic acid polymorphisms, Rs920778, Rs4759314, Rs7958904

Core Tip: The late-stage diagnosis and chemoresistance of cholangiocarcinoma has led to an urgent need to identify new diagnostic biomarkers for the early detection of this aggressive malignancy. Homeobox protein transcript antisense intergenic ribonucleic acid polymorphisms have emerged as potential diagnostic biomarkers for several types of cancers. We conducted a case-control study in order to investigate possible associations between three homeobox protein transcript antisense intergenic ribonucleic acid polymorphisms and risk for cholangiocarcinoma development.