Common Bacteria Associated With Gastric Cancer and New Biomarkers

Researchers investigated the expression of two lncRNAs in gastric cancer tissues and evaluated their association with a common strainbacteria.

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Gastric cancer (GC) is the fifth most common cancer worldwide. Risk factors include alcohol, salt-preserved foods, obesity, smoking, red meat, and helicobacter pylori (H. pylori). H. pylori is a gram-negative bacterium and the strongest risk factor for developing GC. These are not uncommon bacteria. H. pylori can be found in the stomachs of approximately half the world’s population.

“It was reported that treatment of H. pylori infection in patients with early gastric cancer reduced the risk of developing gastric cancer by 50% [6]. A meta-analysis of six randomized trials revealed that treatment of H. pylori infection in general population may prevent developing of gastric cancer by a cancer relative risk of 0.66 [7].”

Aside from H. pylori infection, certain long non-protein coding RNAs (lncRNAs) have been implicated in the pathogenesis of GC. The maternally expressed gene 3 (MEG3) lncRNA is a tumor suppressor gene. Downregulation of MEG3 has been observed in many types of cancer, including GC. Transversely, the Hox transcript antisense intergenic RNA (HOTAIR) lncRNA acts as a tumor oncogene and has been shown to be upregulated in primary and metastatic GC. MEG3 and HOTAIR are two well-studied lncRNAs that have a demonstrated association with GC development and progression. However, neither 1) the diagnostic potential of MEG3 and HOTAIR nor 2) the association between MEG3 and HOTAIR expression and H. pylori infection in GC have been fully investigated.

The Study

In a new study, researchers Farnaz Amini, Mohammad Khalaj-Kondori, Amin Moqadami, and Ali Rajabi from the University of Tabriz aimed to investigate MEG3 and HOTAIR expression in a cohort of GC patients and explore their association with H. pylori infection. They also explored potential correlations between lncRNA expression and clinicopathological features of GC. On February 10, 2022, Genes & Cancer published their research paper, entitled, “Expression of HOTAIR and MEG3 are negatively associated with H. pylori positive status in gastric cancer patients.”

“Here we aimed to investigate the expression of MEG3 and HOTAIR in gastric cancer tissues and evaluate their association with the H. pylori status.”

The researchers obtained 100 gastric tumor and adjacent non-tumor tissue samples from Noor-E-Nejat Hospital in Tabriz, Iran. The majority of patients were H. pylori positive (55%), female (68%) and half were younger than 50 years old. The team extracted total RNA from the samples and cDNA was synthesized. Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) analysis was used to assess the expression levels of MEG3 and HOTAIR in the GC tissues. To evaluate the biomarker potency of MEG3 and HOTAIR, they used receiver operating characteristic (ROC) curve analysis. The association of MEG3 and HOTAIR expression with H. pylori status and other GC clinicopathological characteristics were investigated. 

“Furthermore, sensitivity and specificity of the MEG3 and HOTAIR expression levels for discrimination of the tumor and non-tumor samples were evaluated by Receiver operating characteristic (ROC) curve analysis.”

Results

Compared to the non-tumor tissues, the researchers found that HOTAIR was upregulated and MEG3 was downregulated in the tumor tissues. Samples were investigated to determine a potential correlation between HOTAIR and MEG3 expression in GC. Their results suggested that a higher expression level of HOTAIR might lead to the downregulation of MEG3. There was also a significant negative association between the expression levels of these lncRNAs and H. pylori positive status. Interestingly, only the expression level of HOTAIR was significantly associated with the size and stage of GC tumors. The ROC curve analysis revealed that the expression levels of MEG3 and HOTAIR may be capable of discerning GC tumor tissues from non-tumor tissues.

“Furthermore, the diagnostic potential of the two lncRNAs was investigated by ROC curve analysis. The results showed that MEG3 and HOTAIR expression levels could discriminate tumor from non-tumor tissues with specificities 86% and 74%, and sensitivities 79% and 84% respectively.”

Conclusion

This study revealed a negative association between H. pylori infection and MEG3 and HOTAIR expression. Additionally, the researchers observed a negative association between MEG3 and HOTAIR expression. The findings of this study add to the current understanding of the role of lncRNAs in cancer pathogenesis, specifically in GC development and progression. Furthermore, this research suggests that MEG3 and HOTAIR expression may serve as potential diagnostic biomarkers for GC. Future studies are warranted to validate these findings in larger cohorts of GC patients.

Click here to read the full research paper, published by Genes & Cancer.

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