SPP1 promotes ovarian cancer progression via Integrin &amp;beta;1/FAK/Akt signaling pathway

Zeng, Biao; Zhou, Ming; Wu, Huan; Xiong, Zhengai

doi:10.2147/ott.s154215

Cited by 97 publications

(67 citation statements)

References 45 publications

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“…[24]. Elevated expression of SPP1 has been observed in multiple cancers, including colon cancer, lung cancer, prostate cancer, breast cancer, ovarian cancer, multiple myeloma, acute myeloid leukaemia, and chronic myeloid leukaemia [25][26][27]. SPP1 expression was also higher in cervical cancer [28].…”

Section: Discussionmentioning

confidence: 99%

A Five-Genes-Based Prognostic Signature for Cervical Cancer Overall Survival Prediction

Zhao

Huang

Zou

et al. 2020

International Journal of Genomics

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Aims. This study is aimed at identifying a prognostic signature for cervical cancer. Main Methods. The gene expression data and clinical information of cervical cancer and normal cervical tissues were acquired from The Cancer Genome Atlas and from three datasets of the Gene Expression Omnibus database. DESeq2 and Limma were employed to screen differentially expressed genes (DEGs). The overlapping DEGs among all datasets were considered the final DEGs. Then, the functional enrichment analysis was performed. Moreover, the Cox proportional hazards regression was performed to establish a prognostic signature of the DEGs. The Kaplan-Meier analysis was applied to test the model. Relationships between gene expression and clinicopathological parameters in cervical cancer, including age, HPV status, histology, stage, and lymph node metastasis, were analysed by the chi-square test. The somatic mutations of these prognostic genes were assessed through cBioPortal. The robustness of the model was verified in another two independent validation cohorts. Key Findings. In total, 169 overlapping upregulated genes and 29 overlapping downregulated genes were identified in cervical cancer compared with normal cervical tissues. Functional enrichment analysis indicated that the DEGs were mainly enriched in DNA replication, the cell cycle, and the p53 signalling pathway. Finally, a 5-gene- (ITM2A, DSG2, SPP1, EFNA1, and MMP1) based prognostic signature was built. According to this model, each patient was given a prognostic-related risk value. The Kaplan-Meier analysis showed that a higher risk was related to worse overall survival in cervical cancer, with an area under the receiver operating characteristic curve of 0.811 for 15 years. The validity of this model in the prediction of cervical cancer outcome was verified in another two independent datasets. In addition, our study also found that the low expression of ITM2A was associated with cervical adenocarcinoma. Interestingly, DSG2 was associated with the HPV status of cervical cancer. Significance. Our study constructed a prognostic model in cervical cancer and discovered two novel genes, ITM2A and DSG2, associated with cervical carcinogenesis and survival.

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Section: Discussionmentioning

confidence: 99%

A Five-Genes-Based Prognostic Signature for Cervical Cancer Overall Survival Prediction

Zhao

Huang

Zou

et al. 2020

International Journal of Genomics

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“…Compared with that in normal ovarian tissues, SPP1 expression is higher in epithelial ovarian cancer. Its silencing can inhibit cell proliferation, invasion, and migration by regulating the Akt signaling pathway [13]. These results indicate that SPP1 inhibition can obstruct p-Akt and inactivate the PI3K/Akt signaling pathway.…”

Section: Discussionmentioning

confidence: 79%

Transcriptomic analysis reveals that bromodomain containing 9 controls signaling pathways in gastric cancer

Wang

et al. 2020

Preprint

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Abstract Background According to the Cancer Genome Atlas, gastric cancers involve 30% BRD9 changes. Studying the signaling net controlled by BRD9 is important and provides useful information for the treatment of patients with gastric cancer and BRD9 alteration. Objective We performed this study to find the signaling pathways controlled by BRD9 in gastric cancer cells. Methods MGC-803 and AGS cells were selected as BRD9 overexpression and normal expression models, respectively, and added with BRD9 inhibitors BI9564 and BI7273, respectively. RNA-seq and limma R language were used to obtain differentially expressed genes (DEGs), and heatmap R language was employed for cluster analysis. Database for Annotation, Visualization and Integrated Discovery (DAVID) was applied to identify the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments, and STRING database was utilized to construct the protein–protein interaction (PPI) networks. Analysis was performed through Cytoscape software to determine the possible signaling pathway and target genes. Results Group MGC-803: 1204 and 1338 DEGs were found in MGC-803 cells added with BI9564 and BI7273, respectively, and 425 DEGs were found in the intersection of these two sets. AGS group: 974 and 1006 DEGs were found in AGS cells added with BI9564 and BI7273, respectively, and 382 DEGs were found in the intersection of these two sets. The DEG number in the intersection of groups MGC-803 and AGS was only 12, and only 3 of which showed the same regulation direction. Hence, these two types of gastric cancers are greatly altered in the signaling network. GO enrichment and KEGG signaling pathway analyses showed that in group MGC-803, BRD9 mainly controls cell adhesion molecule (CAM) pathway, and genes SPP1 and GNAO1 may play important an important role in the BRD9 controlling network. In group AGS, BRD9 mainly controls protein digestion and absorption pathway, and genes AR and GNGT2 have an important function in the BRD9 controlling network. Conclusion Comprehensive bioinformatics analyses were conducted to screen the DEGs and signaling pathways controlled by BRD9 in different gastric cancer cells. The findings provide a theoretical basis in curing patients with clinical gastric cancer.

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“…Some studies suggested that SPP1 played an important role in the progression and metastasis of several types of cancers. In a study about ovarian cancer, SPP1 was found to be overexpressed in ovarian cancer tissues and promote ovarian cancer progression (12). The overexpression of SPP1 was also found in colorectal cancer tissues and related to poor prognosis (13).…”

Section: Introductionmentioning

confidence: 99%

A Case-Control Study of the Association Between the SPP1 Gene SNPs and the Susceptibility to Breast Cancer in Guangxi, China

Liang

Pan

et al. 2019

Front. Oncol.

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Secreted phosphoprotein-1 (SPP1) has been reported to be involved in the pathogenesis of breast cancer (BRC), but the influence of SPP1 single nucleotide polymorphisms on the BRC susceptibility has been rarely reported. In this study, we explored the association between rs11730582, rs2853750, and rs35893069 in the SPP1 gene and the BRC susceptibility. We used Snapshot assay to detect SPP1 single nucleotide polymorphisms in 471 BRC patients and 471 controls. The plasma SPP1 level was measured by ELISA. We found that the CC genotype and C allele of rs11730582 were associated with a significantly decreased BRC risk compared with the TT genotype and T allele, respectively [CC vs. TT: odds ratio (OR) = 0.59, 95% CI = 0.37-0.94, P = 0.026; C vs. T: OR = 0.79, 95% CI = 0.65-0.96, P = 0.022]. In addition, BRC patients and controls with the rs11730582 CC genotype had a lower plasma SPP1 level than did BRC patients and controls with TT genotype (P = 0.007 and P = 0.011, respectively). Moreover, the proportions of rs11730582 CC genotype and C allele were decreased in BRC patients with clinical stages I-III compared with those with clinical stage IV (P = 0.012 and P = 0.003, respectively). Besides, the C-G-T haplotype was associated with a significantly decreased BRC risk compared with the T-AT haplotype (OR = 0.69, 95% CI = 0.52-0.93, P = 0.015). However, there was no significant association between rs2853750 or rs35893069 and the BRC risk. In summary, our study found the association between rs11730582 and the risk of BRC and suggested that rs11730582 may promote the occurrence and development of BRC by regulating SPP1 expression.

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SPP1 promotes ovarian cancer progression via Integrin β1/FAK/Akt signaling pathway

Cited by 97 publications

References 45 publications

A Five-Genes-Based Prognostic Signature for Cervical Cancer Overall Survival Prediction

A Five-Genes-Based Prognostic Signature for Cervical Cancer Overall Survival Prediction

Transcriptomic analysis reveals that bromodomain containing 9 controls signaling pathways in gastric cancer

A Case-Control Study of the Association Between the SPP1 Gene SNPs and the Susceptibility to Breast Cancer in Guangxi, China

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