Association of Osteopontin Gene Polymorphisms with Colorectal Cancer

Kamal, Ahmed A. M.; Darwish, Rania K.; Saad, Samar; Salama, Mohamed; ElBaradie, Tarek Sherif; Mahmoud, Heba; Elshiwy, Yasmine

doi:10.1080/07357907.2016.1247454

Cited by 10 publications

(7 citation statements)

References 26 publications

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“…The adipokine genes investigated were selected from those adipokines reported to be associated with CRC . The mRNA expression data of the following adipokine‐encoding genes were used: adiponectin gene (ADIPOQ), adiponectin receptor 1 gene (ADIPOR1), adiponectin receptor 2 gene (ADIPOR2), leptin gene (LEP), leptin receptor gene (LEPR), resistin gene (RETN), resistin‐like beta gene (RETNLB), retinol‐binding protein 4 gene (RBP4), SFRP5 (SFRP5; secreted frizzled‐related protein 5), nicotinamide phosphoribosyl transferase gene (NAMPT, encoding visfatin), and secreted phosphoprotein gene 1 (SPP1, encoding osteopontin) (https://www.genenames.org/).…”

Section: Methodsmentioning

confidence: 99%

Upregulation of the adipokine genes ADIPOR1 and SPP1 is related to poor survival outcomes in colorectal cancer

Choe

Chai

et al. 2018

Journal of Surgical Oncology

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Section: Methodsmentioning

confidence: 99%

Upregulation of the adipokine genes ADIPOR1 and SPP1 is related to poor survival outcomes in colorectal cancer

Choe

Chai

et al. 2018

Journal of Surgical Oncology

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“…It is elevated in tumors for progression and metastasis, and its alternatively spliced variants are related to many malignant traits in cancers, such as epithelial-mesenchymal plasticity, cancer cell stemness, chemoresistance, and radioresistance [15][16][17][18][19][20]. However, the variants of SPP1 due to aberrantly processing may cause autoimmune reactions in tumors, which can lead to better outcomes in partial patients [21,22]. In HCC, SPP1 is a validated prognostic biomarker, and it may induce chemoresistance through regulation of autophagy in HCC cells [23,24].…”

Section: Discussionmentioning

confidence: 99%

Machine Learning for Building Immune Genetic Model in Hepatocellular Carcinoma Patients

Liu

Chen

2021

Journal of Oncology

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Background. Hepatocellular carcinoma (HCC) is the leading liver cancer with special immune microenvironment, which played vital roles in tumor relapse and poor drug responses. In this study, we aimed to explore the prognostic immune signatures in HCC and tried to construct an immune-risk model for patient evaluation. Methods. RNA sequencing profiles of HCC patients were collected from the cancer genome Atlas (TCGA), international cancer genome consortium (ICGC), and gene expression omnibus (GEO) databases (GSE14520). Differentially expressed immune genes, derived from ImmPort database and MSigDB signaling pathway lists, between tumor and normal tissues were analyzed with Limma package in R environment. Univariate Cox regression was performed to find survival-related immune genes in TCGA dataset, and in further random forest algorithm analysis, significantly changed immune genes were used to generate a multivariate Cox model to calculate the corresponding immune-risk score. The model was examined in the other two datasets with recipient operation curve (ROC) and survival analysis. Risk effects of immune-risk score and clinical characteristics of patients were individually evaluated, and significant factors were then used to generate a nomogram. Results. There were 52 downregulated and 259 upregulated immune genes between tumor and relatively normal tissues, and the final immune-risk model (based on SPP1, BRD8, NDRG1, KITLG, HSPA4, TRAF3, ITGAV and MAP4K2) can better differentiate patients into high and low immune-risk subpopulations, in which high score patients showed worse outcomes after resection ( p < 0.05 ). The differentially enriched pathways between the two groups were mainly about cell proliferation and cytokine production, and calculated immune-risk score was also highly correlated with immune infiltration levels. The nomogram, constructed with immune-risk score and tumor stages, showed high accuracy and clinical benefits in prediction of 1-, 3- and 5-year overall survival, which is useful in clinical practice. Conclusion. The immune-risk model, based on expression of SPP1, BRD8, NDRG1, KITLG, HSPA4, TRAF3, ITGAV, and MAP4K2, can better differentiate patients into high and low immune-risk groups. Combined nomogram, using immune-risk score and tumor stages, could make accurate prediction of 1-, 3- and 5-year survival in HCC patients.

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“…42,43 In fact, SPP1 isoforms mainly SPP1c was associated with worse survival outcomes. [44][45][46][47] While the -156G.GG polymorphism of spp1 gene is associated with high cancer risk, the presence of -66T.G SNP may act as a protective factor for human cancers; whereas -443T.C mutation in spp1 promoter is not associated with cancer risk. 46 In case of CRC, mutations in spp1 promoter (rs9138 and rs1126616) were shown to be significant contributors to increased risk of developing CRC.…”

Section: Discussionmentioning

confidence: 99%

“…46 In case of CRC, mutations in spp1 promoter (rs9138 and rs1126616) were shown to be significant contributors to increased risk of developing CRC. 42,44 Similarly, the presence of spp1 promoter SNPs -443 (rs11730582) and -1748 (rs2728127) was associated with the aggressiveness of breast cancer. 48 Taken together, several SPP1 molecular subtypes with different structures, intracellular localization and Figure 5.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of Osteopontin (SPP1) in colorectal carcinoma requires a personalized molecular approach

et al. 2019

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Stratification of colorectal cancer for better management and tangible clinical outcomes is lacking in clinical practice. To reach this goal, the identification of reliable biomarker(s) is a prerequisite to deliver personalized colorectal cancer theranostics. Osteopontin (SPP1) is a key extracellular matrix protein involved in several pathophysiological processes including cancer progression and metastasis. However, the exact molecular mechanisms regulating its expression, localization, and molecular functions in cancer are still poorly understood. This study was designed to investigate the SPP1 expression profiles in Saudi colorectal cancer patients, and to assess its prognostic value. Hundred thirty-four (134) archival paraffin blocks of colorectal cancer were collected from King Abdulaziz University Hospital, Saudi Arabia. Tissue microarrays were constructed, and automated immunohistochemistry was performed to evaluate SPP1 protein expression patterns in colorectal cancer. About 20% and 23% of our colorectal cancer samples showed high SPP1 cytoplasmic and nuclear expression patterns, respectively. Cytoplasmic SPP1 did not correlate with age, gender, tumor size, and location. However, significant correlations were observed with tumor grade ( p = 0.008), tumor invasion ( p = 0.01), and distant metastasis ( p = 0.04). Kaplan–Meier survival analysis showed a significantly lower recurrence rate in patients with higher SPP1 cytoplasmic expression ( p = 0.05). At multivariate analysis, high SPP1 cytoplasmic expression was an independent favorable prognostic marker ( p = 0.02). However, nuclear SPP1 expression did not show any prognostic value ( p = 0.712). Our results showed a particular SPP1 prognostic relevance that is not in line with most colorectal cancer previous studies that may be attributed to the molecular pathophysiology of our colorectal cancer cohort. Saudi Arabia has both specific genomic makeup and particular environment that could lead to distinctive molecular roots of cancer. SPP1 has several isoforms, tissue localizations and molecular functions, signaling pathways, and downstream molecular functions. Therefore, a more individualized approach for CRC studies and particularly SPP1 prognosis outcomes’ assessment is highly recommended toward precision oncology.

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Association of Osteopontin Gene Polymorphisms with Colorectal Cancer

Cited by 10 publications

References 26 publications

Upregulation of the adipokine genes ADIPOR1 and SPP1 is related to poor survival outcomes in colorectal cancer

Upregulation of the adipokine genes ADIPOR1 and SPP1 is related to poor survival outcomes in colorectal cancer

Machine Learning for Building Immune Genetic Model in Hepatocellular Carcinoma Patients

Prognostic value of Osteopontin (SPP1) in colorectal carcinoma requires a personalized molecular approach

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