Research Article: Correlation between macrophage migration inhibitory factor and autophagy in Helicobacter pylori-associated gastric carcinogenesis

Date Published: February 11, 2019

Publisher: Public Library of Science

Author(s): Kichul Yoon, Nayoung Kim, Youngmi Park, Bo Kyung Kim, Ji Hyun Park, Cheol Min Shin, Dong Ho Lee, Young-Joon Surh, Masaru Katoh.

http://doi.org/10.1371/journal.pone.0211736

Abstract

The role of macrophage migration inhibitory factor (MIF) and autophagy in gastric cancer is not clear. We determined H. pylori infection status of the subjects and investigated the expression of MIF and autophagy markers (Atg5, LC3A and LC3B) in human gastric tissue at baseline. Then H. pylori eradication was done for H. pylori positive patients and MIF and Atg5 levels were investigated on each follow-up for both H. pylori-eradicated and H. pylori negative patients. Baseline tissue mRNA expression of MIF, Atg5, LC3A and LC3B was measured by real-time PCR in 453 patients (control 165, gastric dysplasia 82, and gastric cancer 206). Three hundred three patients (66.9%) had H. pylori infection at the time of enrollment. Only within H. pylori-positive group, MIF level was significantly elevated in patients with cancer than in control or dysplasia groups (P<0.05). LC3A and LC3B levels also showed significant differences within H. pylori-positive subgroups. H. pylori-positive dysplasia subgroup showed significantly lower (LC3A) (P<0.05) and higher (LC3B) mRNA levels (P<0.05) than in other subgroups. On follow-up, within H. pylori-eradicated group, Atg5 expression increased sequentially from control to dysplasia and cancer subgroups. Multiple linear regression showed autophagy markers (LC3A, LC3B, and Atg5) directly predicted MIF level (adjusted R2 = 0.492, P<0.001). Serial follow-up showed longitudinal increase in Atg5 level in general, with constantly higher levels in H. pylori-eradicated group than in -negative group. Intestinal metaplasia (IM) group initially showed higher Atg5 expression than the IM-negative group. However, it was reversed between the groups eventually because of the lower rate of increase in IM group. These results suggest a role of MIF and autophagy markers and their interaction in H. pylori-associated gastric carcinogenesis.

Partial Text

Gastric cancer is one of the most prevalent cancer types worldwide, particularly in East Asian populations [1]. Gastric dysplasia is a direct precancerous lesion representing the penultimate stage in gastric carcinogenesis [2]. The role of Helicobacter pylori (H. pylori) in the development of gastric dysplasia and cancer has been extensively studied. However, the underlying mechanism in human tissue still remains elusive [3].

MIF level was significantly elevated in cancer subgroup than in control or dysplasia subgroups of patients, only within H. pylori-positive group. Within the H. pylori-positive group, the LC3A and LC3B levels showed significant differences within H. pylori-positive subgroups. Similarly, Atg5 expression increased sequentially from control to dysplasia, and to cancer subgroups within the H. pylori-positive group. Multiple linear regression analysis showed autophagy markers (LC3A, LC3B, and Atg5) directly predicted MIF level (adjusted R2 = 0.492, P < 0.001). Serial follow-up showed longitudinal increase in Atg5 level in general, with constantly higher levels in H. pylori-eradicated group than in -negative group. Taken together, our results suggest the role of MIF and autophagy markers and their interaction in H. pylori-associated gastric carcinogenesis. Indeed, this is the first report suggesting an important distinction between H. pylori-positive and -negative gastric tumorigenesis in terms of MIF and autophagy.   Source: http://doi.org/10.1371/journal.pone.0211736

 

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