Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 21, 2019; 25(15): 1828-1839
Published online Apr 21, 2019. doi: 10.3748/wjg.v25.i15.1828
Lysyl oxidase and hypoxia-inducible factor 1α: biomarkers of gastric cancer
Ya-Lin Han, Li Chen, Rui Qin, Guan-Qing Wang, Xiao-Hua Lin, Guang-Hai Dai
Ya-Lin Han, Li Chen, Rui Qin, Guan-Qing Wang, Guang-Hai Dai, Department of Medical Oncology, Chinese PLA General Hospital, Beijing 100853, China
Xiao-Hua Lin, Department of Oncology, the General Hospital of PLA Rocket Force, Beijing 100088, China
Author contributions: Dai GH and Chen L designed and provided ideas for the project; Han YL wrote and edited the manuscript; Han YL, Chen L and Qin R performed immunohistochemical staining; Han YL analyzed all the data; Han YL and Lin XH conducted RNA separation, cDNA synthesis and qRT-PCR analysis; Han YL, Qin R and Wang GQ collected clinical samples from our hospital.
Supported by the grants from the Military Medical Science and Technology Youth Training Program Project (16QNP146).
Institutional review board statement: This study was conducted with permission from the Institutional Research Ethics Committee of Chinese PLA General Hospital.
Institutional animal care and use committee statement: This study did not include the animal experiments.
Conflict-of-interest statement: The authors declare no potential conflicts of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: This study did not include the animal experiments.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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:
Corresponding author: Guang-Hai Dai, PhD, Professor, Department of Medical Oncology, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China.
Telephone: +86-10-66937231
Received: January 19, 2019
Peer-review started: January 21, 2019
First decision: February13, 2019
Revised: February 21, 2019
Accepted: March 1, 2019
Article in press: March 2, 2019
Published online: April 21, 2019

Gastric cancer (GC) is one of the main causes of cancer mortality worldwide. Recent studies on tumor microenvironments have shown that tumor metabolism exerts a vital role in cancer progression.


To investigate whether lysyl oxidase (LOX) and hypoxia-inducible factor 1α (HIF1α) are prognostic and predictive biomarkers in GC.


A total of 80 tissue and blood samples were collected from 140 patients admitted to our hospital between August 2008 and March 2012. Immunohistochemical staining was performed to measure the expression of LOX and HIF1α in tumor and adjacent tissues collected from patients with GC. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was used to detect the mRNA expression levels of LOX and HIF1α in patients with GC. In addition, single-factor analysis was applied to analyze the relationship between LOX, HIF1α and prognosis of GC.


Immunohistochemical staining suggested that the expression levels of LOX and HIF1α increased in tumor tissues from patients with GC. QRT-PCR analysis indicated that mRNA expression of LOX and HIF1α was also upregulated in tumor tissues, which was in accordance with the above results. We also detected expression of these two genes in blood samples. The expression level of LOX and HIF1α was higher in patients with GC than in healthy controls. Additional analysis showed that the expression level of LOX and HIF1α was related to the clinicopathological characteristics of GC. Expression of LOX and HIF1α increased with the number of lymph node metastases, deeper infiltration depth and later tumor–node–metastasis stages. Single-factor analysis showed that high expression of LOX and HIF1α led to poor prognosis of patients with GC.


LOX and HIF1α can be used as prognostic and predictive biomarkers for GC.

Keywords: Lysyl oxidase, Hypoxia-inducible factor 1α, Gastric cancer, Biomarker, Prognosis

Core tip: Lysyl oxidase (LOX) is a secreted extracellular matrix protein that plays an important role in remodeling the extracellular matrix and promoting tumor progression. The LOX family comprises the prototypic LOX, as well as the LOX-like proteins that are involved in carcinogenesis. Hypoxia-inducible factor 1α (HIF1α) is a type of transcription factor complex that has the capacity to regulate oxygen tension. In addition, HIF1α is able to activate or bind to multiple target genes and participates in inflammatory and other diseases. HIF1α accelerates the growth and metastasis of hepatocellular carcinoma.