Low expression of the GOPC is a poor prognostic marker in colorectal cancer

Ohara, Nobuyoshi; Haraguchi, Naotsugu; Koseki, Junichi; Nishizawa, Yujiro; Kawai, Kenji; Takahashi, Hidekazu; Nishimura, Junichi; Hata, Taishi; Mizushima, Tsunekazu; Yamamoto, Hirofumi; Ishii, Hideshi; Doki, Yuichiro; Mori, Masaki

doi:10.3892/ol.2017.6817

Cited by 8 publications

(3 citation statements)

References 33 publications

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“…Actually, studies on the role of GOPC, PAEP and IDE in STAD are mostly lacking, but they all have important roles in other cancer types. Therefore, more preliminary single-gene bioinformatics analysis is needed to validate their functions in STAD ( Yfanti et al, 2008 ; Dydensborg et al, 2009 ; Ohara et al, 2017 ). These previous studies demonstrate, from a different perspective, that the inclusion of these seven modular genes in our signature is reasonable and reliable.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Role of M6A-Associated Immune Genes and Cluster-Related Tumor Microenvironment Analysis: A Multi-Omics Practice in Stomach Adenocarcinoma

Luo

Zhang

et al. 2022

Front. Cell Dev. Biol.

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N6-methylandrostenedione (m6A) methylation plays a very important role in the development of malignant tumors. The immune system is the key point in the progression of tumors, particularly in terms of tumor treatment and drug resistance. Tumor immunotherapy has now become a hot spot and a new approach for tumor treatment. However, as far as the stomach adenocarcinoma (STAD) is concerned, the in-depth research is still a gap in the m6A-associated immune markers. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases is extremely important for our research, where we obtained gene mutation, gene expression data and relevant clinical information of STAD patients. Firstly, the samples from GEO were used as external validation groups, while the TCGA samples were divided into a training group and an internal validation group randomly. Using the way of Single factor COX-LASSO- and multi-factor Cox to construct the prognostic model. Then, all samples were subjected to cluster analysis to generate high and low expression groups of immune gene. Meanwhile, we also collected the correlation between these types and tumor microenvironment. On this basis, a web version of the dynamic nomogram APP was developed. In addition, we performed microenvironmental correlation, copy number variation and mutation analyses for model genes. The prognostic model for STAD developed here demonstrated a very strong predictive ability. The results of cluster analysis manifested that the immune gene low expression group had lower survival rate and higher degree of immune infiltration. Therefore, the immune gene low expression group was associated with lower survival rates and a higher degree of immune infiltration. Gene set enrichment analysis suggested that the potential mechanism might be related to the activation of immunosuppressive functions and multiple signaling pathways. Correspondingly, the web version of the dynamic nomogram APP produced by the DynNom package has successfully achieved rapid and accurate calculation of patient survival rates. Finally, the multi-omics analysis of model genes further enriched the research content. Interference of RAB19 was confirmed to facilitate migration of STAD cells in vitro, while its overexpression inhibited these features. The prognostic model for STAD constructed in this study is accurate and efficient based on multi-omics analysis and experimental validation. Additionally, the results of the correlation analysis between the tumor microenvironment and m6Ascore are the basics of further exploration of the pathophysiological mechanism in STAD.

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Section: Discussionmentioning

confidence: 99%

Prognostic Role of M6A-Associated Immune Genes and Cluster-Related Tumor Microenvironment Analysis: A Multi-Omics Practice in Stomach Adenocarcinoma

Luo

Zhang

et al. 2022

Front. Cell Dev. Biol.

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“…LASSO and subsequent multivariate Cox regression analyses identified a signature composed of six innate IRGs (SREBF2, GP2, BMX, NR1H4, DDX41, GOPC) as being significantly BMX, 30,31 GP2, 32 DDX41 [33][34][35] and NR1H4 [36][37][38][39] have been reported to correlate positively and GOPC negatively with tumor-related phenotypes and adverse events in several types of cancer. 40 Bone marrow X kinase (BMX) was associated with chemoresistance in SCLC through its modulation of autophagy. 30 Moreover, BMX signaling was found to mediate radiation resistance in the vascular endothelium of lung tumors in mice.…”

Section: Discussionmentioning

confidence: 99%

Identification of an Innate Immune-Related Prognostic Signature in Early-Stage Lung Squamous Cell Carcinoma

Li¹,

Xue²,

Ma³

et al. 2021

IJGM

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Background: Early-stage lung squamous cell carcinoma (LUSC) progression is accompanied by changes in immune microenvironments and the expression of immune-related genes (IRGs). Identifying innate IRGs associated with prognosis may improve treatment and reveal new immunotherapeutic targets. Methods: Gene expression profiles and clinical data of early-stage LUSC patients were obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases and IRGs from the InnateDB database. Univariate and multivariate Cox regression and LASSO regression analyses were performed to identify an innate IRG signature model prognostic in patients with early-stage LUSC. The predictive ability of this model was assessed by timedependent receiver operator characteristic curve analysis, with the independence of the model-determined risk score assessed by univariate and multivariate Cox regression analyses. Overall survival (OS) in early-stage LUSC patients was assessed using a nomogram and decision curve analysis (DCA). Functional and biological pathways were determined by gene set enrichment analysis, and differences in biological functions and immune microenvironments between the high-and low-risk groups were assessed by ESTIMATE and the CIBERSORT algorithm. Results: A signature involving six IRGs (SREBF2, GP2, BMX, NR1H4, DDX41, and GOPC) was prognostic of OS. Samples were divided into high-and low-risk groups based on median risk scores. OS was significantly shorter in the high-risk than in the low-risk group in the training (P < 0.001), GEO validation (P = 0.00021) and TCGA validation (P = 0.034) cohorts. Multivariate Cox regression analysis showed that risk score was an independent risk factor for OS, with the combination of risk score and T stage being optimally predictive of clinical benefit. GSEA, ESTIMATE, and the CIBERSORT algorithm showed that immune cell infiltration was higher and immune-related pathways were more strongly expressed in the low-risk group. Conclusion: A signature that includes these six innate IRGs may predict prognosis in patients with early-stage LUSC.

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“…Immunohistochemical staining was performed as previously described. 24 We assessed syntenin-1 protein expression by immunohistochemical staining of formalin‑fixed and paraffin‑embedded normal colorectal mucosa and colorectal cancer tissue sections. The surgical tissue samples were incubated overnight at room temperature in 10% formalin, and then embedded in paraffin.…”

Section: Methodsmentioning

confidence: 99%

Syntenin-1 promotes colorectal cancer stem cell expansion and chemoresistance by regulating prostaglandin E2 receptor

et al. 2020

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Background The protein syntenin-1 is expressed by a variety of cell types, and is upregulated in various malignancies, including melanoma, breast cancer and glioma. Although the mechanism by which elevated syntenin-1 expression contributes to cancer has been described, the exact pathway has not been elucidated. Methods To investigate the involvement of syntenin-1 in colorectal cancer (CRC), we performed immunohistochemical analysis of 139 CRC surgical specimens. We also examined syntenin-1 knockdown in CRC cell lines. Results High syntenin-1 expression was associated with less differentiated histologic grade and poor prognosis, and was an independent prognostic indicator in CRC. Syntenin-1 knockdown in CRC cells reduced the presence of cancer stem cells (CSCs), oxaliplatin chemoresistance and migration. DNA microarray analysis and quantitative real-time polymerase chain reaction showed decreased prostaglandin E2 receptor 2 (PTGER2) expression in syntenin-1-knockdown cells. PTGER2 knockdown in CRC cells yielded the same phenotype as syntenin-1 knockdown. Celecoxib, which has anti-inflammatory effects by targeting cyclooxygenase-2, reduced CSCs and decreased chemoresistance, while prostaglandin E2 (PGE2) had the opposite effect. Conclusions Our findings suggested that syntenin-1 enhanced CSC expansion, oxaliplatin chemoresistance and migration capability through regulation of PTGER2 expression. Syntenin-1 may be a promising new prognostic factor and target for anti-cancer therapies.

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Low expression of the GOPC is a poor prognostic marker in colorectal cancer

Cited by 8 publications

References 33 publications

Prognostic Role of M6A-Associated Immune Genes and Cluster-Related Tumor Microenvironment Analysis: A Multi-Omics Practice in Stomach Adenocarcinoma

Prognostic Role of M6A-Associated Immune Genes and Cluster-Related Tumor Microenvironment Analysis: A Multi-Omics Practice in Stomach Adenocarcinoma

Identification of an Innate Immune-Related Prognostic Signature in Early-Stage Lung Squamous Cell Carcinoma

Syntenin-1 promotes colorectal cancer stem cell expansion and chemoresistance by regulating prostaglandin E2 receptor

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