Identification of hub genes correlated with the pathogenesis and prognosis of gastric cancer via bioinformatics methods

Nie, Kechao; Shi, Laner; Wen, Yi; Pan, Jinglin; Li, Peiwu; Zheng, Zhihua; Liu, Fengbin

doi:10.23736/s0026-4806.19.06166-4

Cited by 43 publications

(35 citation statements)

References 57 publications

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“…COL3A1, which encodes pro-alpha1 chains of type III collagen, could form homotrimeric fibrils to play its role. Except for normal localization in connective tissues, COL3A1 was also found to be highly expressed in various cancers including bladder cancer, glioblastoma, and gastric cancer (22)(23)(24). In breast cancer, it was reported that stromal COL3A1 expression was significantly increased from benign breast tumors to malignant breast tumors (18).…”

Section: Discussionmentioning

confidence: 99%

Reduced Expression of METTL3 Promotes Metastasis of Triple-Negative Breast Cancer by m6A Methylation-Mediated COL3A1 Up-Regulation

et al. 2020

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The abnormal m6A modification caused by m6A modulators is a common feature of various tumors; however, little is known about which m6A modulator plays the most important role in triple-negative breast cancer (TNBC). In this study, when analyzing the influence of m6A modulators ( METTL3, METTL14, WTAP, FTO , and ALKBH5 ) on the prognosis of breast cancer, especially in TNBC using several on-line databases, methyltransferase-like 3 ( METTL3 ) was found to have low expression in breast cancer, and was closely associated with short-distance-metastasis-free survival in TNBC. Further investigation showed that knockdown of METTL3 could enhance the ability of migration, invasion, and adhesion by decreasing m6A level in TNBC cell lines. Collagen type III alpha 1 chain ( COL3A1 ) was identified and verified as a target gene of METTL3 . METTL3 could down-regulate the expression of COL3A1 by increasing its m6A methylation, ultimately inhibiting the metastasis of TNBC cells. Finally, with immunohistochemistry staining in breast cancer tissues, it was proved that METTL3 expression was negatively correlated with COL3A1 in TNBC, but not in non-TNBC. This study demonstrated the potential mechanism of m6A modification in metastasis and provided potential targets for treatment in TNBC.

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Section: Discussionmentioning

confidence: 99%

Reduced Expression of METTL3 Promotes Metastasis of Triple-Negative Breast Cancer by m6A Methylation-Mediated COL3A1 Up-Regulation

et al. 2020

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“…Interestingly, BCAM levels are significantly higher in primary GC tumors of patients with metastasis and predict a worse overall survival and increase cell migration, invasion and metastasis by mediating tumor-ECM interactions [105,138]. COL3A1 is a type III collagen and part of the interstitial matrix regulating stromal components and is up-regulated in GC versus normal stomach tissue and is a marker of poor prognosis in many cancer types [106,107,139,140]. ECM protein CCN1 is a DCLK1 kinasedependent sEV cargo protein and is down-regulated upon overexpres- suggesting that our observations in MKN1 cells are not restricted to a particular cell type.…”

Section: Discussionmentioning

confidence: 99%

Cancer stem cell marker DCLK1 reprograms small extracellular vesicles toward migratory phenotype in gastric cancer cells

et al. 2021

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Doublecortin-like kinase 1 (DCLK1) is a putative cancer stem cell marker, a promising diagnostic and prognostic maker for malignant tumors and a proposed driver gene for gastric cancer (GC). DCLK1 overexpression in a majority of solid cancers correlates with lymph node metastases, advanced disease and overall poor-prognosis. In cancer cells, DCLK1 expression has been shown to promote epithelial-to-mesenchymal transition (EMT), driving disruption of cell-cell adhesion, cell migration and invasion. Here, we report that DCLK1 influences small extracellular vesicle (sEV/exosome) biogenesis in a kinase-dependent manner. sEVs isolated from DCLK1 overexpressing human GC cell line MKN1 (MKN1 OE -sEVs), promote the migration of parental (non-transfected) MKN1 cells (MKN1 PAR ). Quantitative proteome analysis of MKN1 OE -sEVs revealed enrichment in migratory and adhesion regulators (STRAP, CORO1B, BCAM, COL3A, CCN1) in comparison to MKN1 PAR -sEVs. Moreover, using DCLK1-IN-1, a specific small molecule inhibitor of DCLK1, we reversed the increase in sEV size and concentration in contrast to other EV subtypes, as well as kinase-dependent cargo selection of proteins involved in EV biogenesis (KTN1, CHMP1A, MYO1G) and migration and adhesion processes (STRAP, CCN1). Our findings highlight a specific role of DCLK1-kinase dependent cargo selection for sEVs and shed new light on its role as a regulator of signaling in gastric tumorigenesis.

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“…It has been considered as an independent prognostic factor for GC, which is consistent with our results[ 25 ]. Furthermore, CGB5 is correlated with a poor prognosis in patients with advanced GC[ 26 , 27 ]. It has been reported that LGR6 might be involved in the development of GC via the PI3K/AKT/mTOR axis[ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of an immune-related gene-based signature to predict prognosis of patients with gastric cancer

Qiu¹,

Song²,

Liu³

et al. 2020

WJGO

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BACKGROUND Gastric cancer (GC) is the most commonly diagnosed malignancy worldwide. Increasing evidence suggests that it is necessary to further explore genetic and immunological characteristics of GC. AIM To construct an immune-related gene (IRG) signature for accurately predicting the prognosis of patients with GC. METHODS Differentially expressed genes (DEGs) between 375 gastric cancer tissues and 32 normal adjacent tissues were obtained from The Cancer Genome Atlas (TCGA) GDC data portal. Then, differentially expressed IRGs from the ImmPort database were identified for GC. Cox univariate survival analysis was used to screen survival-related IRGs. Differentially expressed survival-related IRGs were considered as hub IRGs. Genetic mutations of hub IRGs were analyzed. Then, hub IRGs were selected to conduct a prognostic signature. Receiver operating characteristic (ROC) curve analysis was used to evaluate the prognostic performance of the signature. The correlation of the signature with clinical features and tumor-infiltrating immune cells was analyzed. RESULTS Among all DEGs, 70 hub IRGs were obtained for GC. The deletions and amplifications were the two most common types of genetic mutations of hub IRGs. A prognostic signature was identified, consisting of ten hub IRGs (including S100A12, DEFB126, KAL1, APOH, CGB5, GRP, GLP2R, LGR6, PTGER3 , and CTLA4 ). This prognostic signature could accurately distinguish patients into high- and low- risk groups, and overall survival analysis showed that high risk patients had shortened survival time than low risk patients ( P < 0.0001). The area under curve of the ROC of the signature was 0.761, suggesting that the prognostic signature had a high sensitivity and accuracy. Multivariate regression analysis demonstrated that the prognostic signature could become an independent prognostic predictor for GC after adjustment for other clinical features. Furthermore, we found that the prognostic signature was significantly correlated with macrophage infiltration. CONCLUSION Our study proposed an immune-related prognostic signature for GC, which could help develop treatment strategies for patients with GC in the future.

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Identification of hub genes correlated with the pathogenesis and prognosis of gastric cancer via bioinformatics methods

Cited by 43 publications

References 57 publications

Reduced Expression of METTL3 Promotes Metastasis of Triple-Negative Breast Cancer by m6A Methylation-Mediated COL3A1 Up-Regulation

Reduced Expression of METTL3 Promotes Metastasis of Triple-Negative Breast Cancer by m6A Methylation-Mediated COL3A1 Up-Regulation

Cancer stem cell marker DCLK1 reprograms small extracellular vesicles toward migratory phenotype in gastric cancer cells

Identification of an immune-related gene-based signature to predict prognosis of patients with gastric cancer

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