Oncological Effects and Prognostic Value of AMAP1 in Gastric Cancer

PurposeWe examined the diagnostic significance, prognostic value, and potential function of AMAP1 in gastric cancer (GC).MethodsComprehensive bioinformatic analysis was conducted to investigate differential expression of AMAP1 mRNA and protein in GC. Meta-analyses were utilized to determine the overall prognostic correlation of AMAP1 mRNA in patients with GC. A panel of vitro assays was applied to assess target microRNA and AMAP1 protein in GC cell lines and tissues, respectively.ResultsAMAP1 mRNA and protein levels were upregulated in GC specimens, compared to matched normal tissues. AMAP1 mRNA exhibited promising results regarding differential diagnosis of GC and normal tissue. Meta-analysis based on the TCGA and GEO databases revealed that high AMAP1 mRNA abundance was associated with poor overall survival (HR = 1.42; 95% CI: 1.06–1.89) and was correlated with reduced progression-free survival (HR = 1.89; 95% CI: 1.51–2.36) in GC patients. Moreover, AMAP1 was negatively correlated with miR-192-3p (r = −0.3843; P < 0.0001). A dual-luciferase assay revealed that miR-192-3p targeted AMAP1. Levels of miR-192-3p were significantly higher in GC tissues and GC cells than in normal tissues and cells. Moreover, AMAP1 silencing resulted in reduced GC proliferation, migration, and invasion.ConclusionAMAP1 is a novel oncogene in GC and is negatively correlated with by miR-192-3p. AMAP1 may act as a diagnostic and prognostic marker of GC.

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Prognostic Role of the Circulating Tumor Cells Detected by Cytological Methods in Gastric Cancer: A Meta-Analysis

BioMed Research International ◽

10.1155/2016/2765464 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Kun Zou ◽

Shuailong Yang ◽

Liang Zheng ◽

Shuyi Wang ◽

Bin Xiong

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Prognostic Value ◽

Meta Analysis ◽

Progression Free Survival ◽

High Status ◽

Poor Overall Survival ◽

Free Survival ◽

Gastric Cancer Patients

Objective. We performed a meta-analysis of available studies to assess the prognostic value of circulating tumor cells detected by cytological methods for patients with gastric cancer. Methods. Two authors systematically searched the studies independently with key words in PubMed, MEDLINE, EMBASE, Science Citation Index Expanded, and Cochrane Library (from inception to April 2016). The estimated hazard ratio, risk ratio, odds ratio, and their 95% confidence intervals were set as effect measures. All analyses were performed by STATA 12.0. Results. Sixteen studies were included in this meta-analysis. CTCs-high status was significantly associated with poor overall survival (HR=2.23, 95% CI: 1.86–2.66) and progression-free survival (HR=2.02, 95% CI: 1.36–2.99). CTCs-high status was also associated with depth of infiltration (OR = 2.07, 95% CI: 1.16–3.70), regional lymph nodes metastasis (OR = 1.85, 95% CI: 1.26–2.71), and distant metastasis (OR = 2.83, 95% CI: 1.77–4.52). For unresectable gastric cancer patients, CTCs-high status was significantly associated with poor overall survival, progression-free survival, and disease control rate before and during chemotherapy group. Conclusions. Our meta-analysis has evidenced the significant prognostic value of CTCs detected for both PFS and OS in gastric cancer patients. For patients treated with chemotherapy alone, we proved that CTCs detected by cytological method showed a significant prognostic value and poor response to chemotherapy.

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Distinctive Prognostic Value and Cellular Functions of Osteopontin Splice Variants in Human Gastric Cancer

Cells ◽

10.3390/cells10071820 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1820

Author(s):

Chengcheng Hao ◽

Yuxin Cui ◽

Jane Lane ◽

Shuqin Jia ◽

Jiafu Ji ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Prognostic Value ◽

Splice Variants ◽

Tnm Staging ◽

Migration And Invasion ◽

Ros Production ◽

Gastric Cancer Cells ◽

Normal Tissues

Background: Osteopontin (OPN) splice variants are identified as predictors of tumour progression and therapeutic resistance in certain types of solid tumours. However, their roles in gastric cancer (GC) remain poorly characterized. The current study sought to assess the prognostic value of the three OPN splice variants (namely OPN-a, OPN-b, and OPN-c) in gastric cancer and their potential functions within gastric cancer cells. Methods: RNA extraction and reverse transcription were performed using our clinical cohort of gastric carcinomas and matched normal tissues (n = 324 matched pairs). Transcript levels were determined using real-time quantitative PCR. Three OPN splice variants overexpressed cell lines were created from the gastric cancer cell line HGC-27. Subsequently, biological functions, including cell growth, adhesion, migration, and invasion, were studied. The potential effects of OPN isoforms on cisplatin and 5-Fu were evaluated by detecting cellular reactive oxygen species (ROS) levels in the HGC-27-derived cell lines. Results: Compared with normal tissues, the expression levels of three splice variants were all elevated in gastric cancer tissues in an order of OPN-a > OPN-b > OPN-c. The OPN-a level significantly increased with increasing TNM staging and worse clinical outcome. There appeared to be a downregulation for OPN-c in increasing lymph node status (p < 0.05), increasing TNM staging, and poor differentiation. High levels of OPN-a and OPN-b were correlated with short overall survival and disease-free survival of gastric cancer patients. However, the low expression of OPN-c was significantly associated with a poor prognosis. Functional analyses further showed that ectopic expression of OPN-c suppressed in vitro proliferation, adhesiveness, migration, and invasion properties of HGC-27 cells, while the opposite role was seen for OPN-a. Cellular ROS detection indicated that OPN-a and OPN-c significantly promoted ROS production after treatment with 5-Fu comparing to OPN-vector, while only OPN-a markedly induced ROS production after treatment with cisplatin. Conclusion: Our results suggest that OPN splice variants have distinguished potential to predict the prognosis of gastric cancer. Three OPN variants exert distinctive functions in gastric cancer cells. Focusing on specific OPN isoforms could be a novel direction for developing diagnostic and therapeutic approaches in gastric cancer.

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circLMTK2 acts as a sponge of miR-150-5p and promotes proliferation and metastasis in gastric cancer

Molecular Cancer ◽

10.1186/s12943-019-1081-4 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 15

Author(s):

Sen Wang ◽

Dong Tang ◽

Wei Wang ◽

Yining Yang ◽

Xiaoqing Wu ◽

...

Keyword(s):

Gastric Cancer ◽

Bioinformatic Analysis ◽

Migration And Invasion ◽

Circular Rnas ◽

Normal Tissues ◽

Tumour Metastasis ◽

Genome Wide ◽

Proliferation And Metastasis

Abstract Background As a novel class of non-coding RNAs, circular RNAs (circRNAs) are key regulators of the development and progression of different cancers. However, little is known about the function and biological mechanism of circLMTK2, also named hsa_circ_0001725, in gastric cancer (GC) tumourigenesis. Methods circLMTK2 was identified in ten paired cancer specimens and adjacent normal tissues by RNA sequencing and genome-wide bioinformatic analysis and verified by quantitative real-time PCR (qRT-PCR). Knockdown or exogenous expression of circLMTK2 combined with in vitro and in vivo assays were performed to prove the functional significance of circLMTK2. The molecular mechanism of circLMTK2 was demonstrated by searching the CircNet database and confirmed by RNA in vivo precipitation assays, western blotting, luciferase assays and rescue experiments. Results circLMTK2 was frequently upregulated in GC tissues, and high circLMTK2 expression was associated with poor prognosis, lymph node metastasis and poor TNM stage in GC patients. Functionally, circLMTK2 overexpression promoted GC cell proliferation and tumourigenicity in vitro and in vivo. Furthermore, ectopic circLMTK2 expression enhanced GC cell migration and invasion in vitro and tumour metastasis in vivo. In addition, we demonstrated that circLMTK2 could sponge miR-150-5p, thus indirectly regulating the c-Myc expression and contributing to GC tumourigenesis. Conclusion Our findings demonstrate that circLMTK2 functions as a tumour promoter in GC through the miR-150-5p/c-Myc axis and could thus be a prognostic predictor and therapeutic target for GC.

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Identification of MATN3 as a Novel Prognostic Biomarker for Gastric Cancer through Comprehensive TCGA and GEO Data Mining

Disease Markers ◽

10.1155/2021/1769635 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Pan Wang ◽

Wei-sheng Xiao ◽

Yue-hua Li ◽

Xiao-ping Wu ◽

Hong-bo Zhu ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Poor Prognosis ◽

Prognostic Value ◽

Prognostic Biomarker ◽

Meta Analysis ◽

Progression Free Survival ◽

Free Survival ◽

The World ◽

Diagnostic And Prognostic Value

Gastric cancer (GC) is still a vital malignant cancer across the world with unsatisfactory prognostic results. Matrilin-3 (MATN3) is a member of the extracellular matrix (ECM) protein family. The present research intends to explore the expression level of MATN3 in patients with GC and to explore the prognosis significance of MATN3. In this study, we observed that the MATN3 expression was remarkably upregulated in GC samples in contrast to noncancer samples. Clinical analyses unveiled that high MATN3 expression was related to age, tumor status, and clinical stages. Survival analyses unveiled that patients with high MATN3 expression displayed a poorer overall survival and progression-free survival than those with low MATN3 expression. The AUC of the relevant ROC curve for 1 year, 3 years, and 5 years of survival is 0.571, 0.596, and 0.720, separately. Multivariate assays revealed that MATN3 expression and stage were independent predictors of poor prognosis of GC patients. A meta-analysis unveiled that high MATN3 expression was tightly associated with better overall survival. Overall, our data indicated that MATN3 may have a diagnostic and prognostic value for patients with advanced gastric cancer and assist to improve clinical outcomes for GC patients.

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Prognostic value of the C-reactive protein to albumin ratio in colorectal cancer: an updated systematic review and meta-analysis

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02253-y ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Chun-Kai Liao ◽

Yen-Lin Yu ◽

Yueh-Chen Lin ◽

Yu-Jen Hsu ◽

Yih-Jong Chern ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Prognostic Value ◽

Meta Analysis ◽

Disease Free Survival ◽

Progression Free Survival ◽

Poor Overall Survival ◽

Free Survival ◽

Pre Treatment ◽

Disease Free

Abstract Backgrounds The inflammatory biomarker “C-reactive protein to albumin ratio (CAR)” has been reported to significantly correlate to a variety of human cancers. However, there are conflicting results regarding the prognostic value of CAR in colorectal cancer. Previous studies mainly assessed patients in Eastern countries, so their findings may not be applicable to the Western population. Therefore, this updated meta-analysis aimed to investigate the prognostic value of pre-treatment CAR and outcomes of patients with colorectal cancer. Methods We conducted a systematic search for eligible literature until October 31, 2020, using PubMed and Embase databases. Studies assessing pre-treatment CAR and outcomes of colorectal cancer were included. Outcome measures included overall survival, disease-free survival, progression-free survival, and clinicopathological features. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used as effective values. Results A total of 15 studies involving 6329 patients were included in this study. The pooled results indicated that a high pre-treatment CAR was associated with poor overall survival (HR 2.028, 95% CI 1.808−2.275, p < 0.001) and poor disease-free survival/progression-free survival (HR 1.768, 95% CI 1.321–2.365, p < 0.001). Subgroup analysis revealed a constant prognostic value of the pre-treatment CAR despite different study regions, sample size, cancer stage, treatment methods, or the cut-off value used. We also noted a correlation between high pre-treatment CAR and old age, male sex, colon cancer, advanced stage (III/IV), large tumor size, poor differentiation, elevated carcinoembryonic antigen levels, neutrophil-to-lymphocyte ratio, and the modified Glasgow prognostic score. Conclusions High pre-treatment CAR was associated with poor overall survival, disease-free survival, and progression-free survival in colorectal cancer. It can serve as a prognostic marker for colorectal cancer in clinical practice.

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Circular RNA _0008278 acts as a sponge of miR-378 and promotes proliferation and metastasis in gastric cancer

10.21203/rs.3.rs-335561/v1 ◽

2021 ◽

Author(s):

Xuan Li ◽

Haisheng Qian ◽

Hao Dong ◽

Yini Dang ◽

Lei Peng ◽

...

Keyword(s):

Gastric Cancer ◽

Bioinformatic Analysis ◽

Potential Method ◽

Circular Rna ◽

Migration And Invasion ◽

Normal Tissues ◽

Tumour Metastasis ◽

Regulatory Molecule

Abstract Background: Circular RNA (circRNA) is rising as an indispensable regulatory molecule in the progression of various kinds of malignant growth. However, little is known about the capacity and instruments of circRNA_0008727 in gastric cancer (GC). Our point was to recognize a novel circRNA-microRNA-mRNA useful system in gastric cancer. Method: CircRNA_0008278 was identified in three paired cancer specimens and adjacent normal tissues by RNA sequencing and genome-wide bioinformatic analysis and verified by quantitative real-time PCR (qRT-PCR). Knockdown or exogenous expression of circRNA_0008278 combined with in vitro and in vivo assays were performed to prove the functional significance of circRNA_0008278. The molecular mechanism of circRNA_0008278 was demonstrated by searching the CircNet database and confirmed by RNA in vivo precipitation assays, western blotting, luciferase assays and rescue experiments.Results: CircRNA_0008278 was frequently upregulated in GC tissues, and high circRNA_0008278 expression was associated with poor prognosis, lymph node metastasis and poor TNM stage in GC patients. Functionally, circRNA_0008278 overexpression promoted GC cell proliferation and tumourigenicity in vitro and in vivo. Furthermore, circRNA_0008278 over-expression enhanced GC cell migration and invasion in vitro and tumour metastasis in vivo. In addition, we demonstrated that circRNA_0008278 could sponge miR-378, thus indirectly regulating theYY1 expression and contributing to GC tumourigenesis.Conclusion: Our findings demonstrate that circRNA_0008278 functions as a tumour promoter in GC, and a new pathway circRNA_0008278/miR-378/YY1 which may be potential method for gastric cancer treatment.

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Identification CXCL9 is a Potential Prognostic Biomarker in Ovarian and Gastric Cancer and is Correlated with Immune Infiltrates

10.21203/rs.3.rs-350037/v1 ◽

2021 ◽

Author(s):

Tinghui Wu ◽

Yongchao Li ◽

Shujuan Gong ◽

Ruijun Shi ◽

Hangzheng Zhou ◽

...

Keyword(s):

Gastric Cancer ◽

Dendritic Cells ◽

Immune Cell ◽

Mrna Level ◽

Progression Free Survival ◽

Cytotoxic Lymphocytes ◽

Poor Overall Survival ◽

Normal Tissues ◽

Microarray Database ◽

Kaplan Meier

Abstract Background CXCL9 also known as an interferon gamma-inducible chemokine that belonging to the CXC chemokine family. It plays a role in promoting chemotaxis, inducing leukocyte differentiation and multiplication, and triggering tissue extravasation. Methods The TIMER (Tumor Immune Estimation Resource) and cancer microarray database Oncomine were used to dig at CXCL9 expression. The clinic prognostic level of CXCL9 was evaluated via Kaplan-Meier plotter. Then, Using TIMER and GEPIA, we investigated whether CXCL9 expression impacted cancer immune infiltrates. Results CXCL9 expression has been found to be significantly lower in ovarian and gastric cancers relative to normal tissues. In patients with ovarian cancer (OS HR = 0.78, P = 0.0017; PFS HR = 0.85, R = 0.015) and gastric cancer (OS HR = 0.55, P = 1.1e-08; PFS HR = 0.58, R = 7.6e-07), low CXCL9 expression was correlation to PFS (progression-free survival) and OS (poor overall survival). Furthermore, in OV and GC, CXCL9 was shown to have a close interaction with tumor-infiltrating immunity cells (B cells, CD4 + and CD8 + T cells, macrophages, neutrophils, and dendritic cells). CXCL9 expression, on the other hand, was shown to be closely related to several immune markers. Conclusion In OV and GC, CXCL9 mRNA level is strongly associated with prognosis and levels of penetration tumor-infiltrating immunity cell. The CXCL9 expression may also play a role in controlling TAMs (tumor-associated macrophages), DCs (Dendritic cells), CTLs (cytotoxic lymphocytes), and NK (natural killer) cells in OV and GC. CXCL9 may be seen as an independent marker that assesses the prognosis in OV and GC patients. Besides, CXCL9 expression level also can assess the immune cell subtypes of tumor microenvironment in OV and GC.

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The Cancer-Testis Long Non-coding RNA PCAT6 Facilitates the Malignant Phenotype of Ovarian Cancer by Sponging miR-143-3p

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.593677 ◽

2021 ◽

Vol 9 ◽

Author(s):

Xiaofang Tan ◽

Yang Shao ◽

Yue Teng ◽

Siyu Liu ◽

Weijian Li ◽

...

Keyword(s):

Ovarian Cancer ◽

Transforming Growth Factor ◽

Progression Free Survival ◽

Bioinformatic Analysis ◽

Migration And Invasion ◽

Small Rna Sequencing ◽

Loss Of Function ◽

Poor Overall Survival ◽

Inhibition Of Proliferation ◽

Skov3 Cells

Background: It has been reported that long non-coding RNAs (lncRNAs) play critical roles in tumorigenesis. However, their roles in ovarian cancer (OC) remain to be elucidated. The aim of this study was to uncover the function and underlying mechanisms of PCAT6 in OC.Methods: The expression pattern of PCAT6 in OC was analyzed in the GSE137238, GSE143897 and Gene Expression Profile Interactive Analysis (GEPIA) datasets. Kaplan–Meier Plotter online software was used for survival analysis. Loss-of-function assays and gain-of-function assays were used to assess the function of PCAT6 in OC development. Moreover, small-RNA sequencing, bioinformatic analysis, luciferase assays and rescue experiments were carried out to clarify the potential mechanism of PCAT6 in OC.Results: PCAT6 expression was significantly increased in OC tissues and positively correlated with advanced stages and with poor overall survival, progression-free survival and post-progression survival. Knockdown of PCAT6 in A2780 and SKOV3 cells inhibited OC cell proliferation, migration and invasion. In contrast, Overexpression of PCAT6 exerted the opposite effects on OC cells. Notably, PCAT6 bound to miR-143-3p and affected the expression of transforming growth factor (TGF)-β-activated kinase 1 (TAK1). Subsequent rescue assays confirmed that upregulation of miR-143-3p decreased the PCAT6 overexpression-induced promotion of proliferation, migration and invasion. Moreover, downregulation of miR-143-3p reversed the PCAT6 knockdown-induced inhibition of proliferation, migration, and invasion.Conclusions: Our findings demonstrate that PCAT6 plays an oncogenic role in OC and may be useful as a therapeutic target for OC.

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The Clinical Significance and Prognostic Value of HER2 Expression in Bladder Cancer: A Meta-Analysis and a Bioinformatic Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.653491 ◽

2021 ◽

Vol 11 ◽

Author(s):

Kai Gan ◽

Yue Gao ◽

Kuangzheng Liu ◽

Bin Xu ◽

Weijun Qin

Keyword(s):

Bladder Cancer ◽

Clinical Significance ◽

Prognostic Value ◽

Meta Analysis ◽

Growth Factor Receptor ◽

Bioinformatic Analysis ◽

Tumor Stage ◽

Her2 Expression ◽

Large Tumor ◽

Normal Tissues

ObjectiveHuman Epidermal Growth Factor Receptor 2 (HER2) is highly expressed in multiple malignancies and associated with patients’ prognosis, but its role in bladder cancer (BCa) remains elusive. We conducted this meta-analysis to explore the clinical significance and prognostic value of HER2 in BCa.MethodsPubMed was searched for studies published between January 1, 2000 and January 1, 2020. The odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95%CIs) were used to investigate the relationship between HER2 and BCa pathological features. TCGA was mined for the information regarding as well.ResultsOur study included 14 articles enrolling 1398 people. Expression of HER2 is higher in bladder cancer than in normal tissues. HER2 over-expression is associated with CIS, multifocal tumor, large tumor size, high tumor stage and grade, lymph node metastasis, progression, recurrence and papillary tumor. We could not find a significant association between HER2 expression and survival time in BCa patients.ConclusionsOur meta and bioinformatic analysis indicated that HER2 expression was related to pathological malignancy and poor prognosis in BCa.

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Identification CXCL9 is a Potential Prognostic Biomarker in Ovarian and Gastric Cancer and is Correlated with Immune Infiltrates

10.21203/rs.3.rs-350037/v2 ◽

2021 ◽

Author(s):

Shuwei Li ◽

Ruijun Shi ◽

Hangzheng Zhou ◽

Dongyang Wang ◽

Kunlong Zhu ◽

...

Keyword(s):

Gastric Cancer ◽

Dendritic Cells ◽

Immune Cell ◽

Mrna Level ◽

Progression Free Survival ◽

Cytotoxic Lymphocytes ◽

Poor Overall Survival ◽

Normal Tissues ◽

Microarray Database ◽

Kaplan Meier

Abstract Background: CXCL9 also known as an interferon gamma-inducible chemokine that belonging to the CXC chemokine family. It plays a role in promoting chemotaxis, inducing leukocyte differentiation and multiplication, and triggering tissue extravasation. Methods: The TIMER (Tumor Immune Estimation Resource) and cancer microarray database Oncomine were used to dig at CXCL9 expression. The clinic prognostic level of CXCL9 was evaluated via Kaplan-Meier plotter. Then, Using TIMER and GEPIA, we investigated whether CXCL9 expression impacted cancer immune infiltrates. Results: CXCL9 expression has been found to be significantly lower in ovarian and gastric cancers relative to normal tissues. In patients with ovarian cancer (OS HR = 0.78, P = 0.0017; PFS HR = 0.85, R = 0.015) and gastric cancer (OS HR = 0.55, P = 1.1e-08; PFS HR = 0.58, R = 7.6e-07), low CXCL9 expression was correlation to PFS (progression-free survival) and OS (poor overall survival). Furthermore, in OV and GC, CXCL9 was shown to have a close interaction with tumor-infiltrating immunity cells (B cells, CD4+ and CD8+ T cells, macrophages, neutrophils, and dendritic cells). CXCL9 expression, on the other hand, was shown to be closely related to several immune markers.Conclusion: In OV and GC, CXCL9 mRNA level is strongly associated with prognosis and levels of penetration tumor-infiltrating immunity cell. The CXCL9 expression may also play a role in controlling TAMs (tumor-associated macrophages), DCs (Dendritic cells), CTLs (cytotoxic lymphocytes), and NK (natural killer) cells in OV and GC. CXCL9 may be seen as an independent marker that assesses the prognosis in OV and GC patients. Besides, CXCL9 expression level also can assess the immune cell subtypes of tumor microenvironment in OV and GC.

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