Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2020; 26(22): 3024-3033
Published online Jun 14, 2020. doi: 10.3748/wjg.v26.i22.3024
High plasma levels of COL10A1 are associated with advanced tumor stage in gastric cancer patients
Laura Necula, Lilia Matei, Denisa Dragu, Ioana Pitica, Ana Iulia Neagu, Coralia Bleotu, Simona Dima, Irinel Popescu, Carmen C Diaconu, Mihaela Chivu-Economescu
Laura Necula, Lilia Matei, Denisa Dragu, Ioana Pitica, Ana Iulia Neagu, Coralia Bleotu, Carmen C Diaconu, Mihaela Chivu-Economescu, Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
Laura Necula, Titu Maiorescu University, Faculty of Medicine, Bucharest 040441, Romania
Simona Dima, Irinel Popescu, Fundeni Clinical Institute, Bucharest 022328, Romania
Author contributions: Necula L and Matei L equally contributed to this paper. Necula L, Chivu-Economescu M, and Matei L designed research; Dima S and Popescu I treated patients and collected material and clinical data from patients; Necula L, Matei L, Dragu D, and Pitica I performed the assays; Necula L, Matei L, Bleotu C, Diaconu CC, Chivu-and Economescu M analysed data; Necula L, Matei L, Neagu AI, and Chivu-Economescu M wrote the paper.
Supported by the Romanian National Authority for Scientific Research and Innovation, CNCS - UEFISCDI, No. PN-III-P4-ID-PCCF-2016-0158 (contract PCCF 17/2018), within PNCDI III.
Institutional review board statement: The study was reviewed and approved by the Stefan S. Nicolau Institute of Virology.
Conflict-of-interest statement: This work was supported by a grant of the Romanian Authority for Scientific Research and Innovation, CNCS - UEFISCDI, No. PN-III-P4-ID-PCCF-2016-0158 (contract PCCF 17/2018), within PNCDI III. All other authors have nothing to disclose.
Data sharing statement: No additional data are available.
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: Mihaela Chivu-Economescu, PhD, Research Assistant Professor, Research Scientist, Senior Researcher, Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, 285 Mihai Bravu Ave, Bucharest 030304, Romania. mihaela.economescu@virology.ro
Received: December 24, 2019
Peer-review started: December 28, 2019
First decision: January 19, 2020
Revised: May 14, 2020
Accepted: May 28, 2020
Article in press: May 28, 2020
Published online: June 14, 2020
Processing time: 169 Days and 5.9 Hours
ARTICLE HIGHLIGHTS
Research background

Despite the major advances in the field of personalized medicine, gastric cancer (GC) remains an aggressive malignancy with a high rate of mortality, being the third leading cause of cancer-related death. The main issue in the management of this disease is represented by the high molecular heterogeneity that results in the phenotypical aggressiveness of GC and limits the antitumor efficacy of the targeted therapy.

Research motivation

GC is still characterized by late diagnosis, limited effective treatment options, and lack of reliable biomarkers for the patient outcome prediction and response to therapy. The discovery of new circulating biomarkers useful in the early diagnosis of GC is mandatory.

Research objectives

The present study aimed to evaluate the potential of COL10A1 as a circulating biomarker for the diagnosis and prognosis of gastric adenocarcinoma patients.

Research methods

Plasma and tissue samples obtained from 49 patients with gastric adenocarcinoma have been used in exploring the expression of COL10A1. Real-time PCR and western blot techniques were used to evaluate COL10A1 level in gastric tumor tissue compared to normal adjacent tissue. The circulating level of COL10A1 was also evaluated by ELISA in plasma of gastric adenocarcinoma patients. Survival analysis was made in order to evaluate the potential of COL10A1 as a biomarker for the diagnosis and prognosis of gastric adenocarcinoma patients.

Research results

Our results showed a significant increase in COL10A1 gene expression and protein levels in gastric tumor tissue compared to adjacent normal tissue. COL10A1 seems to show an elevated expression from the beginning of carcinogenesis, in the early stages, and its increased level remains elevated during cancer progression. This significant increase of COL10A1 was observed also in plasma of gastric adenocarcinoma patients. Moreover, increased COL10A1 plasma level was associated with poor survival. Plasma COL10A1 performed a diagnostic value in GC with an area under the receiver operating characteristic curve (AUC) of 0.9171 (P = 0.0002), sensitivity of 87.76%, and specificity of 100.0%. Furthermore, this study demonstrated the potential role of plasma COL10A1 in the early detection of GC, as in the early stage we obtained an AUC of 0.8789 (P = 0.0030), sensitivity of 81.25%, and specificity of 100.0%. If confirmed in further studies, circulating COL10A1 level could be considered for treatment decisions in these patients.

Research conclusions

We reported for the first time an increased circulating expression level of COL10A1 in gastric adenocarcinoma patients that is associated with poor survival. The high sensitivity and specificity obtained suggest that COL10A1 could represent a potential biomarker for early detection of GC.

Research perspectives

The identification of circulating biomarkers is important since their detection is non-invasive and can be easily implemented in daily clinical practice without higher costs, being based on such techniques as ELISA. On the other hand, the use of a cheap and specific test for population screening could improve early diagnosis rate and contribute to the decrease of the GC burden.