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Expression of Oncostatin M in Early Gastric Cancer and Precancerous Lesions.

ABSTRACT: Objective:To detect the expression of the Oncostatin M (OSM) gene and encoded protein in the mucosal epithelium of chronic gastritis, intestinal metaplasia (IM), low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), early gastric cancer (EGC), and advanced gastric cancer (AGC) samples and to explore the correlation and clinicopathological significance of OSM expression in the process of gastric carcinogenesis. Methods:The expression levels of OSM in chronic gastritis, IM, LGIN, HGIN, EGC, and AGC samples were detected by gene chip, real-time quantitative PCR, and immunohistochemical methods. The expression levels of OSM in the gastric mucosa were analyzed, and its correlation with clinical pathology was studied. Results:The expression level of OSM in gastric HGIN and EGC tissues was significantly higher than that in LGIN tissues based on expression profiling (P < 0.001). The expression of the OSM gene in EGC was higher than that in HGIN (unpaired t test, P < 0.05) and LGIN (unpaired t test, P < 0.01) by qPCR. The expression of OSM in LGIN was significantly lower than that in HGIN (P = 0.008) and EGC (P = 0.044) by immunohistochemical staining. The expression of OSM in HGIN tissues was significantly higher than that in AGC (P = 0.007). Conclusion:Alterations in the expression of the OSM gene may be involved in the malignant transformation of the gastric mucosal epithelium. Because of the significant difference in the cancerization rate and clinical management between LGIN and HGIN, the difference in the staining intensity of OSM between LGIN and HGIN may be one of the early markers of gastric intraepithelial neoplasia.

SUBMITTER: Shi J

PROVIDER: S-EPMC6913316 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Expression of Oncostatin M in Early Gastric Cancer and Precancerous Lesions.

Shi Jihua J Xu Xue X Du Jun J Cui Haimeng H Luo Qingfeng Q

Gastroenterology research and practice 20191201

<h4>Objective</h4>To detect the expression of the Oncostatin M (OSM) gene and encoded protein in the mucosal epithelium of chronic gastritis, intestinal metaplasia (IM), low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), early gastric cancer (EGC), and advanced gastric cancer (AGC) samples and to explore the correlation and clinicopathological significance of OSM expression in the process of gastric carcinogenesis.<h4>Methods</h4>The expression levels of OSM ...[more]

PMID: 31871447

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Project description:BackgroundAngiogenesis is a pathobiological hallmark of gastric cancer. However, rare studies focus on angiogenesis in gastric precancerous lesions (GPL). Weipixiao (WPX), a Chinese herbal preparation, is proved clinically effective in treating GPL. Here, we evaluated WPX's anti-angiogenic potential for GPL, and also investigated the possibility of its anti-angiogenic mechanisms.MethodsHPLC analysis was applied to screen the major chemical components of WPX. After modeling N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced GPL in male Sprague-Dawley rats, different doses of WPX were administrated orally for 10 weeks. Next, we performed histopathological examination using routine H&E staining and HID-AB-PAS staining. In parallel, we assessed angiogenesis revealed by microvessel density (MVD) using CD34 immunostaining, and subsequently observe microvessel ultrastructure in gastric mucosa under Transmission Electron Microscope. Finally, we detect expression of angiogenesis-associated markers VEGF and HIF-1α using immunohistochemistry. Moreover, mRNA expressions of ERK1, ERK2, Cylin D1 as well as HIF-1α in gastric mucosa were determined by quantitative real-time reverse transcription- polymerase chain reaction.ResultsWe observed the appearance of active angiogenesis in GPL rats, and demonstrated that WPX could reduce microvascular abnormalities and attenuate early angiogenesis in most of GPL specimens with a concomitant regression of most intestinal metaplasia (IM) and a portion of gastric epithelial dysplasia (GED). In parallel, WPX could suppress HIF-1α mRNA expression (P < 0.01) as well as protein expression (although without statistical significance), and could markedly inhibit VEGF protein expression in GPL rats. Mechanistically, WPX intervention, especially at low dose, caused a significant decrease in the ERK1 and Cylin D1 mRNA levels. However, WPX might probably have no regulatory effect on ERK2 amplification.ConclusionsWPX could attenuate early angiogenesis and temper microvascular abnormalities in GPL rats. This might be partly achieved by inhibiting on the angiogenesis-associated markers HIF-1α and VEGF, and on the ERK1/Cylin D1 aberrant activation.

Project description:ObjectiveMicroRNA (miR)-421 plays a key role in cancer progression. It has been reported that circulating miR-421may be a potential tumor marker for the diagnosis of several cancers. However, the role of miR-421 in plasma as a potential biomarker in the diagnosis of precancerous gastric lesions (Pre) and early-stage gastric cancer (GC) remains poorly understood. In this study, we investigated miR-421 in plasma as a novel potential biomarker for the detection of precancerous gastric lesions and early-stage (GC).Materials & methodsThe miRNA content was determined by quantitative real-time polymerase chain reaction (qRT-PCR). MiR-421 content in all subjects was normalized by endogenous miRNA (miR-16). The diagnostic value of miR-421 for Pre and GC was assessed by comparing receiver operating characteristic (ROC) analysis with traditional tumor markers, including CEA, CA125, CA153, CA211 and CA50. The correlation between the expression of miR-421 and the pathological characteristics of Pre and GC was analyzed.ResultsElevated expression of miR-421 in plasma can robustly distinguish the normal population from Pre and GC cases, especially in the early stages of gastric cancer cases (all p < 0.05). The ROC analyses showed that the area under the ROC curve (AUC), sensitivity, accuracy and Youden index of miR-421 were superior to traditional tumor markers (CEA, CA125, CA153, CA211, and CA50) in GC diagnosis, while its specificity was higher than CEA, CA153 and CA50 (all p < 0.05). MiR-421 in plasma had higher AUC value than AFP, CA153, CA211 and CA50 in the diagnosis of Pre (all p < 0.05), while specificity, accuracy and Youden index of miR-421 was only lower than CA211. The efficiency of miR-421 in the diagnosis of GC was significantly higher than that of CA211 and CA50, and it was significantly higher than CA153, CA211 and CA50 in the diagnosis of Pre (all p < 0.05). In addition, up-regulation of miR-421 occurred initially in precancerous gastric lesions as well as in the early stage of GC.ConclusionsOverexpression of plasma miR-421 is a novel biomarker for the detection of precancerous lesions and early gastric cancer.

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Expression of Oncostatin M in Early Gastric Cancer and Precancerous Lesions.

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Expression of Oncostatin M in Early Gastric Cancer and Precancerous Lesions.

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