Clinicopathological features and prognosis of gastric cancer in young patients

Liu, Shushang; Feng, Fan; Xu, Guanghui; Liu, Zhen; Tian, Yangzi; Guo, Man; Lian, Xiao; Cai, Lei; Fan, Daiming; Zhang, Hongwei

doi:10.1186/s12885-016-2489-5

Cited by 77 publications

(99 citation statements)

References 33 publications

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“…Studies have demonstrated that among these ncRNAs, ~18% of lncRNAs are associated with human tumors, compared with only 9% of human protein-coding genes [31], suggesting that lncRNAs could act as major contributors to carcinogenesis and cancer progression. The roles of dysregulated lncRNAs in the proliferation, invasion and migration of many kinds of cancers have garnered increased scientific interest in recent years [32–34]. …”

Section: Discussionmentioning

confidence: 99%

The long non-coding RNA TP73-AS1 modulates HCC cell proliferation through miR-200a-dependent HMGB1/RAGE regulation

Huang

et al. 2017

J Exp Clin Cancer Res

127

115

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BackgroundP73 antisense RNA 1 T (non-protein coding), also known as TP73-AS1, is a long non-coding RNA (lncRNA) which is involved in cell proliferation and the development of tumors. However, the exact effects and molecular mechanisms of TP73-AS1 in hepatocellular carcinoma (HCC) progression are still unknown. The present study is aimed to investigate the detailed functions and the mechanism of TP73-AS1 in regulation of HCC cell proliferation.MethodsTP73-AS1 expression in HCC tissues and cell lines was determined using real-time PCR assays; the correlation of TP73-AS1 expression with clinicopathological features of HCC was analyzed. The functions of TP73-AS1 in regulation of HCC cell proliferation was evaluated using MTT and BrdU assays. The candidate upstream miRNAs of HMGB1 were screened using miRcode, miRWalk, miRanda and Target scan, verified using real-time PCR assays. The interaction between TP73-AS1 and miR-200a was confirmed using Luciferase report gene assays. The proten levels of HMGB1 signaling-related factors in response to co-processing TP73-AS1 knockdown and miR-200a inhibition were determined using Western blot assays and ELISA. Further, miR-200a, HMGB1 mRNA and RAGE mRNA and their correlations in HCC tissues were determined.ResultsTP73-AS1 was upregulated in HCC tissues and cell lines. High TP73-AS1 expression was correlated with worse clinicopathological features, poorer prognosis and shorter survival. Knockdown of TP73-AS1 inhibited the HCC proliferation and the expression levels of HMGB1, RAGE and NF-κB in HCC cells. By using online tools, we screened out several candidate upstream miRNAs of HMGB1, among which miR-200a overexpression inhibited HMGB1 mRNA expression the most significantly. By using luciferase assays, we confirmed that miR-200a could directly bind to TP73-AS1 and the 3’UTR of HMGB1; TP73-AS1 competed with HMGB1 for miR-200a binding. MiR-200a inhibition could up-regulate HMGB1, RAGE, NF-κB expression as well as NF-κB regulated cytokines levels, which could be partially restored by si-TP73-AS1. In HCC tissues, miR-200a was down-regulated while HMGB1 and RAGE were up-regulated; TP73-AS1 was inversely correlated with miR-200a, while positively correlated with HMGB1 and RAGE, respectively.ConclusionOur data indicated that TP73-AS1 might be an oncogenic lncRNA that promoted proliferation of HCC and could be regarded as a therapeutic target in human HCC.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-017-0519-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

The long non-coding RNA TP73-AS1 modulates HCC cell proliferation through miR-200a-dependent HMGB1/RAGE regulation

Huang

et al. 2017

J Exp Clin Cancer Res

127

115

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“…[18,20,21] We found that high HOTAIR expression was related to poor differentiation in estrogen-dependent cancers and OSCCs, although the correlation was not identified in previous studies. [18–21] Our results showed that HOTAIR expression correlated with a larger tumor size, though the statistical significance was only found in cancers of the respiratory system and there was a publication bias, suggesting that large-scale investigations were required. There are several explanations for the discrepancy in predictive role of HOTAIR expression in various types of cancers.…”

Section: Discussionmentioning

confidence: 94%

“…[18–21] Elevated HOTAIR expression is reported to be associated with advanced clinical stage and lymph node metastasis in gastric cancer from a meta-analysis involving 10 studies. [18] However, the relationship between HOTAIR expression and clinical stage is not identified when the data on hepatocellular and gastric cancers are pooled in 4 studies. [20] The clinicopathological value of HOTAIR expression is controversial, and most studies have focused primarily on malignancies of the digestive system.…”

Section: Discussionmentioning

confidence: 99%

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Clinicopathological and prognostic significance of homeobox transcript antisense RNA expression in various cancers

et al. 2017

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Background:Increased expression of the homeobox (HOX) transcript antisense RNA (HOTAIR) has been reported in multiple types of malignancies and enhances the proliferation and migration of cancer cells. However, the association between HOTAIR expression and tumor progression and prognosis remains controversial. We performed a meta-analysis to clarify the association between the expression of HOTAIR and the clinicopathological features and prognosis in different cancers.Methods:A systematic search of the PubMed, Web of Science, EMBASE, and Ovid databases was conducted, up to September 2016, for eligible studies involving HOTAIR expression and malignancies. The odds ratios (ORs), hazard ratios (HRs), and corresponding 95% confidence intervals (CIs) were calculated using fixed- or random-effect models. Any publication bias was evaluated using Begg and Egger tests, and adjusted using the trim and fill method if a bias existed.Results:A total of 4116 patients from 44 studies were included in our meta-analysis. The results showed that high HOTAIR expression was associated with an advanced clinical tumor stage (OR = 3.90, 95% CI = 3.02–5.03, P < .001), lymph node metastasis (OR = 3.11, 95% CI = 2.15–4.49, P < .001), poor differentiation of the tumor (OR = 1.56, 95% CI = 1.01–2.41, P = .03), and worse prognosis (HR = 2.16, 95% CI = 1.73–2.69, P < .001) in different cancer types. HOTAIR expression was more predictive in monitoring the clinical tumor stage of patients and there was no significant heterogeneity or publication bias found in the analysis.Conclusion:Our meta-analysis suggests that HOTAIR is positively correlated with tumor development and negatively correlated with clinical outcome. Thus, an increase in HOTAIR expression may be a potential biomarker for tumor progression and evaluation of prognosis.

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“…Gastric cancer (GC) is the third most frequent cause of cancer‐related deaths worldwide . The incidence of GC increases after the age of 50 years and peaks in the 60s to 70s . Aging is one of the major factors for GC, like other cancers, yet a substantial subgroup of GCs occurs in younger individuals; this cohort is referred to as GC in young adults (GCYA) .…”

Section: Introductionmentioning

confidence: 99%

Enrichment of CLDN18‐ARHGAP fusion gene in gastric cancers in young adults

et al. 2019

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Gastric cancer in young adults has been pointed out to comprise a subgroup associated with distinctive clinicopathological features, including an equal gender distribution, advanced disease, and diffuse‐type histology. Comprehensive molecular analyses of gastric cancers have led to molecular‐based classifications and to specific and effective treatment options. The molecular traits of gastric cancers in young adults await investigations, which should provide a clue to explore therapeutic strategies. Here, we studied 146 gastric cancer patients diagnosed at the age of 40 years or younger at the Cancer Institute Hospital (Tokyo, Japan). Tumor specimens were examined for Helicobacter pylori infection, Epstein‐Barr virus positivity, and for the expression of mismatch repair genes to indicate microsatellite instability. Overexpression, gene amplifications, and rearrangements of 18 candidate driver genes were examined by immunohistochemistry and FISH. Although only a small number of cases were positive for Epstein‐Barr virus and microsatellite instability (n = 2 each), we repeatedly found tumors with gene fusion between a tight‐junction protein claudin, CLDN18 , and a regulator of small G proteins, ARHGAP , in as many as 22 cases (15.1%), and RNA sequencing identified 2 novel types of the fusion. Notably, patients with the CLDN18‐ARHGAP fusion revealed associations between aggressive disease and poor prognosis, even when grouped by their clinical stage. These observations indicate that a fusion gene between CLDN18 and ARHGAP is enriched in younger age‐onset gastric cancers, and its presence could contribute to their aggressive characteristics.

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Clinicopathological features and prognosis of gastric cancer in young patients

Cited by 77 publications

References 33 publications

The long non-coding RNA TP73-AS1 modulates HCC cell proliferation through miR-200a-dependent HMGB1/RAGE regulation

The long non-coding RNA TP73-AS1 modulates HCC cell proliferation through miR-200a-dependent HMGB1/RAGE regulation

Clinicopathological and prognostic significance of homeobox transcript antisense RNA expression in various cancers

Enrichment of CLDN18‐ARHGAP fusion gene in gastric cancers in young adults

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