The Expression Patterns and Prognostic Value of the Proteasome Activator Subunit Gene Family in Gastric Cancer Based on Integrated Analysis

Increasing evidence supports that proteasome activator subunit (PSME) genes play an indispensable role in multiple tumors. The diverse expression patterns, prognostic value, underlying mechanism, and the role in the immunotherapy of PSME genes in gastric cancer (GC) have yet to be fully elucidated. We systematically demonstrated the functions of these genes in GC using various large databases, unbiased in silico approaches, and experimental validation. We found that the median expression levels of all PSME genes were significantly higher in GC tissues than in normal tissues. Our findings showed that up-regulated PSME1 and PSME2 expression significantly correlated with favorable overall survival, post-progression survival, and first progression survival in GC patients. The expression of PSME1 and PSME2 was positively correlated with the infiltration of most immune cells and the activation of anti-cancer immunity cycle steps. Moreover, GC patients with high PSME1 and PSME2 expression have higher immunophenoscore and tumor mutational burden. In addition, a receiver operating characteristic analysis suggested that PSME3 and PSME4 had high diagnostic performance for distinguishing GC patients from healthy individuals. Moreover, our further analysis indicated that PSME genes exert an essential role in GC, and the present study indicated that PSME1 and PSME2 may be potential prognostic markers for enhancing survival and prognostic accuracy in GC patients and may even act as potential biomarkers for GC patients indicating a response to immunotherapy. PSME3 may serve as an oncogene in tumorigenesis and may be a promising therapeutic target for GC. PSME4 had excellent diagnostic performance and could serve as a good diagnostic indicator for GC.

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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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An Integrated Analysis of The Prognosis And Immune Cell Infiltration of ITGB Superfamily Members In Gastric Cancer

10.21203/rs.3.rs-689050/v1 ◽

2021 ◽

Author(s):

Chuan-hong Li ◽

Lei Meng ◽

Zhang-ming Chen ◽

Wan-nian Sui ◽

Pei-feng Chen ◽

...

Keyword(s):

Gastric Cancer ◽

T Cells ◽

Cell Adhesion ◽

Mrna Expression ◽

Cell Lines ◽

Survival Data ◽

Expression Patterns ◽

Expression Level ◽

Integrated Analysis ◽

Expression Levels

Abstract Background:Members of the integrin β superfamily(ITGBs) have been shown to be aberrantly expressed in various human cancers and involved in tumorigenesis and progression. However, the diverse expression patterns and prognostic values of the entire ITGB family members in gastric cancer(GC) has not been systematically investigated.Methods:In the current study, Oncomine, GEPIA, Kaplan Meier plotter, TIMER, GeneMANIA, STRING and Metascape database were employed to explore the transcriptional and survival data of ITGB superfamily members in GC. Moreover, we confirmed the mRNA expression levels of ITGB superfamily members in GC cell lines by qRT-PCR.Results:The mRNA expression level of ITGB1/2/4/5/8 was upregulated in GC, while the expression level of ITGB7 was downregulated. Higher expression of ITGB2/7 was significantly associated with the tumor stage of patients with GC. However, we found that the expression level of ITGB1/2/4/5/6/7/8 was remarkably increased in GC cell lines compared to stomach normal cell lines, while ITGB3 expression was decreased in the former than in the latter. Meanwhile,higher expression levels of ITGB2/6/7 were closely correlated with better overall clinical survival (OS) and recurrence-free survival (RFS) in GC patients, while higher ITGB3/4/5 expression were strongly associated with poorer OS and RFS.We also discovered that the functions of ITGBs and their adjacent genes are mainly related to protein complexes involved in cell adhesion. the functions of ITGBs and their adjacent proteins are mainly related to focal adhesion, cell adhesion molecules, proteoglycans in cancer, small cell lung cancer, rap1 signaling pathway, IgA production by intestinal immune network, and microRNAs in cancer.In addition, the expression of ITGBs was significantly correlated with the infiltration of multiple immune cells, including B cells, CD8+ T cells, CD4+ T cells, neutrophils, macrophages, and dendritic cells.Conclusions:Our results suggested that abnormal expression of ITGBs plays a key role in the progression of GC and that ITGBs may be potential prognostic biomarkers and therapeutic targets for GC.

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Integrated Analysis of the Expression, Prognostic Value, and Relationship with Immune Infiltration of CMTMs in Human Hepatocellular Carcinoma

10.21203/rs.3.rs-891032/v1 ◽

2021 ◽

Author(s):

shitao jiang ◽

Junwei Zhang ◽

Yaoge Liu ◽

Ting Zhang ◽

Lei Zhang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Prognostic Value ◽

Transmembrane Domain ◽

Bioinformatic Analysis ◽

Tumor Stage ◽

Integrated Analysis ◽

Immune Infiltration ◽

Normal Tissues ◽

Precision Therapy ◽

High Level

Abstract The chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing (CMTM) family refers to an updated gene family involved in diverse pathophysiological processes. However, the effect exerted by CMTM family members (CMTMs) in hepatocellular carcinoma (HCC) is still elusive. Herein, to elucidate the expression, prognostic value, and immune roles of CMTMs in HCC, a comprehensive bioinformatic analysis was carried out. Our findings showed that CKLF, CMTM1, CMTM3-4, and CMTM7-8 displayed higher mRNA expression levels in HCC tissues than in normal tissues, yet CMTM2, CMTM5, and CMTM6 were lower in HCC tissues. The levels of CMTM1, CMTM2, and CMTM4 were related to tumor stage. Survival analysis showed that high levels of CKLF, CMTM1, CMTM4, and CMTM6-7 were associated with shorter overall survival (OS). Conversely, a high level of CMTM5 in HCC patients was associated with improved OS. We also found that CKLF, CMTM1-4, and CMTM6-7 were closely correlated with immune infiltration in the HCC microenvironment. In conclusion, this study indicates that CMTMs exert a crucial effect on HCC microenvironment remodeling. CKLF, CMTM1, CMTM4, and CMTM6-7 are potential targets of precision therapy, and CMTM5 is a tumor-suppressive gene that was associated with improved survival in HCC patients.

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A risk score model with five long non-coding RNAs for predicting prognosis in gastric cancer: an integrated analysis combining TCGA and GEO datasets

PeerJ ◽

10.7717/peerj.10556 ◽

2021 ◽

Vol 9 ◽

pp. e10556

Author(s):

Yiguo Wu ◽

Junping Deng ◽

Shuhui Lai ◽

Yujuan You ◽

Jing Wu

Keyword(s):

Gastric Cancer ◽

Risk Score ◽

Prognostic Value ◽

Therapeutic Targets ◽

The Cancer Genome Atlas ◽

Stage Ii ◽

Differentially Expressed ◽

Integrated Analysis ◽

Non Coding Rnas ◽

Score Model

Background Gastric cancer (GC) is one of the most common carcinomas of the digestive tract, and the prognosis for these patients may be poor. There is evidence that some long non-coding RNAs(lncRNAs) can predict the prognosis of patients with GC. However, few lncRNA signatures have been used to predict prognosis. Herein, we aimed to construct a risk score model based on the expression of five lncRNAs to predict the prognosis of patients with GC and provide new potential therapeutic targets. Methods We performed differentially expressed and survival analyses to identify differentially expressed survival-ralated lncRNAs by using GC patient expression profile data from The Cancer Genome Atlas (TCGA) database. We then established a formula including five lncRNAs to predict the prognosis of patients with GC. In addition, to verify the prognostic value of this risk score model, two independent Gene Expression Omnibus (GEO) datasets, GSE62254 (N = 300) and GSE15459 (N = 200), were employed as validation groups. Results Based on the characteristics of five lncRNAs, patients with GC were divided into high or low risk subgroups. The prognostic value of the risk score model with five lncRNAs was confirmed in both TCGA and the two independent GEO datasets. Furthermore, stratification analysis results showed that this model had an independent prognostic value in patients with stage II–IV GC. We constructed a nomogram model combining clinical factors and the five lncRNAs to increase the accuracy of prognostic prediction. Enrichment analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) suggested that the five lncRNAs are associated with multiple cancer occurrence and progression-related pathways. Conclusion The risk score model including five lncRNAs can predict the prognosis of patients with GC, especially those with stage II-IV, and may provide potential therapeutic targets in future.

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Prognostic and immunological role of Fam20C in pan-cancer

Bioscience Reports ◽

10.1042/bsr20201920 ◽

2021 ◽

Vol 41 (1) ◽

Author(s):

Xinpeng Liu ◽

Yuanbo Zhan ◽

Wenxia Xu ◽

Xiaoyao Liu ◽

Yawei Geng ◽

...

Keyword(s):

Prognostic Value ◽

Sequence Similarity ◽

Expression Patterns ◽

The Cancer Genome Atlas ◽

Lower Grade ◽

Tumor Cell Migration ◽

Immune Infiltration ◽

Normal Tissues ◽

Kaplan Meier ◽

Pan Cancer

Abstract Background: The family with sequence similarity 20-member C (Fam20C) kinase plays important roles in physiopathological process and is responsible for majority of the secreted phosphoproteome, including substrates associated with tumor cell migration. However, it remains unclear whether Fam20C plays a role in cancers. Here, we aimed to analyze the expression and prognostic value of Fam20C in pan-cancer and to gain insights into the association between Fam20C and immune infiltration. Methods: We analyzed Fam20C expression patterns and the associations between Fam20C expression levels and prognosis in pan-cancer via the ONCOMINE, TIMER (Tumor Immune Estimation Resource), PrognoScan, GEPIA (Gene Expression Profiling Interactive Analysis), and Kaplan–Meier Plotter databases. After that, GEPIA and TIMER databases were applied to investigate the relations between Fam20C expression and immune infiltration across different cancer types, especially BLCA (bladder urothelial carcinoma), LGG (brain lower grade glioma), and STAD (stomach adenocarcinoma). Results: Compared with adjacent normal tissues, Fam20C was widely expressed across many cancers. In general, Fam20C showed a detrimental role in pan-cancer, it was positively associated with poor survival of BLCA, LGG, and STAD patients. Specifically, based on TCGA (The Cancer Genome Atlas) database, a high expression level of Fam20C was associated with worse prognostic value in stages T2–T4 and stages N0–N2 in the cohort of STAD patients. Moreover, Fam20C expression had positive associations with immune infiltration, including CD4+ T cells, macrophages, neutrophils, and dendritic cells, and other diverse immune cells in BLCA, LGG, and STAD. Conclusion: Fam20C may serve as a promising prognostic biomarker in pan-cancer and has positive associations with immune infiltrates.

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Expression and Prognostic Analysis of Integrins in Gastric Cancer

Journal of Oncology ◽

10.1155/2020/8862228 ◽

2020 ◽

Vol 2020 ◽

pp. 1-19

Author(s):

Jun-Fu Wang ◽

Ye Wang ◽

Si-Wen Zhang ◽

Ye-Yang Chen ◽

Yue Qiu ◽

...

Keyword(s):

Gastric Cancer ◽

Mrna Expression ◽

Prognostic Value ◽

Diagnostic Marker ◽

Receptor Interaction ◽

Sequencing Data ◽

Normal Tissues ◽

Diagnosis And Prognosis ◽

Prognostic Analysis ◽

Kaplan Meier

Background. Integrins are involved in the biological process of a variety of cancers, but their importance in the diagnosis and prognosis of gastric cancer (GC) is still unclear. Therefore, this study aimed at exploring the significance of ITG gene expression in GC to evaluate its diagnosis and prognosis. Methods. GEPIA data were used to evaluate the mRNA expression of ITG genes in GC patients. The prognostic value of these genes was assessed by analyzing their mRNA expression using the Kaplan–Meier curve. The biological function of ITG genes was evaluated by GC tissue sequencing combined with GSEA bioinformatics. Based on the sequencing data, ITGA5 with the largest expression difference was selected for verification, and RT-PCR was used to verify its mRNA expression level in 40 pairs of GC and normal tissues. Results. ITG (A2, A3, A4, A5, A6, A11, AE, AL, AM, AV, AX, B1, B2, B4, B5, B6, and B8) was highly expressed in GC tissues, while ITGA8 was low, compared with their expression in normal tissues. RNA-seq data shows that ITG (A2, A5, A11, AV, and B1) expression was associated with poor prognosis and overall survival. In addition, combined with the results of GC tissue mRNA sequencing, it was further found that the differentially expressed genes in the ITGs genes. ITGA5 was highly expressed in GC tissues compared with its expression in normal tissues, as evaluated by qRT–PCR ( P < 0.001 ) and ROC ( P < 0.001 , AUC (95% CI) = 0.747 (0.641–0.851)), and confirmed that ITGA5 expression was a potential diagnostic marker for GC. Bioinformatics analysis revealed that the signaling pathway involved in ITGA5 was mainly enriched in focal adhesion, ECM-receptor interaction, and PI3K-AKT and was mainly involved in biological processes such as cell adhesion, extracellular matrix, and cell migration. Conclusion. This study suggested that ITGs were associated with the diagnosis and prognosis of GC and discovered the prognostic value and biological role of ITGA5 in GC. Thus, ITGA5 might be used as a potential diagnostic marker for GC.

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Effect of GPC1 on epithelial-to-mesenchymal transition and stemness and interaction with ITGB1 in gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15580 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15580-e15580

Author(s):

Shiqing Wang ◽

Zhenzhen Wu ◽

Minyu Zhou ◽

Wangjun Liao

Keyword(s):

Gastric Cancer ◽

Western Blot ◽

Poor Prognosis ◽

Tumor Metastasis ◽

Epithelial To Mesenchymal Transition ◽

Underlying Mechanism ◽

Mesenchymal Transition ◽

Normal Tissues ◽

Epithelial Marker

e15580 Background: Gastric cancer is the fourth frequently diagnosed cancer worldwide and tumor metastasis plays an important role in its poor prognosis. EMT, which occurs during embryonic development and carcinoma progression, contributes to metastasis and regulates stemness. GPC1, a member of the heparan sulfate proteoglycans family, is overexpressed in many types of cancer, and associates with metastasis and tumor progression. However, it is unknown that the functions of GPC1 and its underlying mechanism in gastric cancer. Methods: Immunohistochemistry analysis was performed in 245 GC tissues to explore the relationship between GPC1 and tumor metastasis. Transwell migration and wound-healing assay were conducted to evaluate the effects of GPC1 on migration and invasiveness. Epithelial marker and mesenchymal markers expression in GC cells were detected by Western blot and immunofluorescence. GPC1 expression induced by TGF-β was detected by Western Blot. After GPC1 was knock downed, the metastatic effect and EMT markers induced by TGF-β were detected. Co-Immunoprecipitation was used to detect the interaction between ITGB1 and GPC1. Results: The expression of GPC1 was higher in GC tissues than in adjacent normal tissues and associated with poor prognosis. Knocking down GPC1 suppressed EMT and stemness which reduced metastasis in vivo and vitro by inhibiting Erk1/2 MAPK and FAK/Akt pathways. TGF-β stimulation significantly upregulated the expression of GPC1 whereas knocking down of GPC1 reversed TGF-β-mediated EMT and stemness. Moreover, we found that knocking down GPC1 could downregulate ITGB1 which was known to promote EMT in gastric cancer. Overexpression of ITGB1 counteracted the influence of knocking down GPC1 on EMT and stemness. Furthermore, GPC1 formed a complex with ITGB1, which indicated that the ability of GPC1 to stimulate EMT is ITGB1-dependent. Conclusions: We conclude that GPC1, through its interaction with ITGB1, plays an important role in regulating TGF-β-mediated EMT and stemness, and could be a potential future therapeutic target to prevent progression of gastric cancer.

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Comprehensive Analysis of IGFBPs as Biomarkers in Gastric Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.723131 ◽

2021 ◽

Vol 11 ◽

Author(s):

Qi Liu ◽

Jianwu Jiang ◽

Xiefu Zhang ◽

Meixiang Zhang ◽

Yang Fu

Keyword(s):

Gastric Cancer ◽

Extracellular Matrix ◽

Overall Survival ◽

Prognostic Value ◽

Expression Patterns ◽

Rectal Adenocarcinoma ◽

Disease Free Survival ◽

Comprehensive Analysis ◽

Free Survival ◽

Disease Free

ObjectiveGastric cancer is the fifth most common cancer worldwide and the third leading cause of cancer-related deaths. Insulin-like growth-factor-binding proteins (IGFBPs) were initially identified as passive inhibitors that combined with insulin-like growth factors (IGFs) in serum. However, more recent data have shown that they have different expression patterns and a variety of functions in the development and occurrence of cancers. Thus, their various roles in cancer still need to be elucidated. This study aimed to explore the IGFBPs and their prognostic value as markers in gastric cancer.MethodsOncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan–Meier Plotter, cBioPortal, GeneMANIA, and TIMER were used to analyze the differential expression, prognostic value, genetic alteration, and association with immune cell infiltration of IGFPBs in gastric cancer.ResultsExpression levels of IGFBP3, IGFBP4, and IGFBP7 were significantly elevated in gastric cancer tissues, whereas those of IGFBP1 were reduced in normal tissues. IGFBP1/5/7 expression was significantly associated with overall survival whereas IGFBP6/7 expression was significantly correlated with disease-free survival in gastric cancer patients. IGFBP3/5/6/7 were associated with clinical cancer stage. Gene ontology and Kyoto Encyclopedia of Genes and Genome analyses showed that IGFBP3/5/7 were mainly enriched in focal adhesion, extracellular matrix structural constituent, cell-substratist junction, extracellular structure, and matrix organization. Stomach adenocarcinoma (STAD) and gastric cancer had more IGFBP1–7 mutations than other tumor types. Hub gene analysis showed that TP53 and IGF2 expression was significantly elevated in STAD patients; PLG, PAPPA, AFP, and CYR61 were associated with overall survival rate; and IGFALS, PLG, IGF1, AHSG, and FN1 were associated with disease-free survival. Finally, IGFBP3–7 were all associated with cancer-associated fibroblast infiltration in STAD, colon adenocarcinoma, and rectal adenocarcinoma.ConclusionOur study provides a comprehensive analysis and selection of IGFBPs as prognostic biomarkers in STAD. This was the first bioinformatic analysis study to describe the involvement of IGFBPs, especially IGFBP7, in gastric cancer development through the extracellular matrix.

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Identification of INHBA as a Potential Biomarker for Gastric Cancer by Comprehensive Analysis

10.21203/rs.3.rs-92167/v2 ◽

2021 ◽

Author(s):

Guangjie Liu ◽

Xiao-jie Hu ◽

Yuxuan Jia ◽

Bing-jie Huo ◽

Cheng Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Signaling Pathway ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Immune Cell ◽

Underlying Mechanism ◽

Bioinformatic Analysis ◽

Tgf Beta ◽

Normal Tissues ◽

Potential Biomarker

Abstract Inhibin subunit beta A (INHBA) is a member of the TGF-beta (transforming growth factor-beta) superfamily proteins, which plays a fundamental role in various cancers. However, little is known about the exact role of INHBA in patients with gastric cancer (GC). The present study aims to explore the relationship between INHBA and GC and detect the underlying mechanisms. Multiple bioinformatic approaches were first preformed basing on TIMER, GEPIA2, GEO, Oncomine and UALCAN databases, which revealed that INHBA was highly elevated in GC. This result was proved by Immunohistochemistry (IHC) and real time polymerase chain reaction (RT-PCR) in 65 cases of GC tissues in our study. The bioinformatic analysis also revealed that high expression of INHBA was significantly related to unfavorable prognosis of GC. To detect the underlying mechanism, further analysis was performed basing on Kaplan Meier plotter database and found that poor prognosis of GC was related to infiltration of different enriched immune-cell subgroups. That was INHBA being negatively correlated with B cell while positively correlated with CD8 + T cells, macrophage, neutrophil and dendritic cell infiltration. However, there was week significant methylation level change between tumor and normal tissues. Moreover, INHBA mainly enriched on cancer-related signaling pathways, including TGF-beta signaling pathway, ECM-receptor signaling pathway, PID ALK1/2 pathway, and AGE-RAGE signaling pathway, which provide a new insight for future in-depth study.

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Prognostic Values for the mRNA Expression of the ADAMTS Family of Genes in Gastric Cancer

Journal of Oncology ◽

10.1155/2020/9431560 ◽

2020 ◽

Vol 2020 ◽

pp. 1-24

Author(s):

Liang Liang ◽

Jin-hui Zhu ◽

Gang Chen ◽

Xin-gan Qin ◽

Jun-qiang Chen

Keyword(s):

Gastric Cancer ◽

Extracellular Matrix ◽

Mrna Expression ◽

Prognostic Value ◽

Kegg Pathway ◽

Meta Analysis ◽

Mrna Level ◽

Expression Levels ◽

Go Annotation ◽

Normal Tissues

The “A Disintegrin and Metalloproteinase with Thrombospondin Motif” (ADAMTS) family of genes is involved in the occurrence and development of different cancers. However, the prognostic value of these genes in gastric cancer (GC) has not been revealed. The present study was thus conducted to determine the prognostic value for the ADAMTS family of genes in GC. First, we evaluated the mRNA expression levels of the ADAMTS family in GC patients using a GEPIA dataset. Thereafter, we determined the prognostic value of these genes by analyzing their mRNA level using the Kaplan–Meier Plotter database. The mRNA expression level of ADAMTS12 was randomly validated by qRT-PCR and meta-analysis while its coexpression genes were derived using Coexpedia. Finally, we performed Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses using the OmicShare Tools. Compared to normal tissues, expression of ADAMTS2 and 12 was significantly higher while that of ADAMTS1, 13, and 15 was significantly lower in GC tissues. According to the RNA-seq and gene chip data, the ADAMTS family (6, 7, 12, 15, and 18) of genes was closely related to the prognosis of GC, and their high expression levels were associated with poor prognosis and survival time. In addition, ADAMTS12 was highly expressed in 20 pairs of GC tissues based on RT-PCR (P=0.016) and meta-analysis (SMD: 0.73, 95% CI: 0.32–1.14, P<0.001). GO and KEGG pathway analyses indicated that the ADAMTS12 coexpressed genes were enriched in the pathways of extracellular matrix organization, extracellular matrix structural constituent, extracellular matrix, and protein digestion and absorption. Herein, we discovered the prognostic values and biological roles of the ADAMTS genes in GC.

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