Clinicopathological Role of Serum-Derived Hyaluronan-Associated Protein (SHAP)-Hyaluronan Complex in Endometrial Cancer

Yabushita, Hiromitsu; Iwasaki, Keita; Kanyama, Kouhei; Obayashi, Yukihiko; Zhuo, Lisheng; Itano, Naoki; Kimata, Koji; Wakatsuki, Akihiko

doi:10.1155/2011/739150

Cited by 6 publications

(5 citation statements)

References 37 publications

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“…ITIH2 (inter-alpha-trypsin inhibitor heavy chain 2), also known as SHAP, complexes with hyaluronan (HA) and plays a role in the inflammatory response. Serum levels of SHAP-HA have been associated with a poor outcome in ovarian and endometrial cancers(44, 45). High Glasgow scores, a measure of systemic inflammation, have been shown to be associated with poor outcomes for NSCLC in both smokers and never smokers, although more pronounced in smokers.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study of Genetic Predictors of Overall Survival for Non–Small Cell Lung Cancer in Never Smokers

Wang

et al. 2013

Cancer Research

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To identify the genetic factors that influence overall survival in never smokers who have non-small cell lung cancer (NSCLC), we performed a consistency meta-analysis study utilizing genome-wide association approaches for overall survival in 327 never smoker NSCLC patients from the MD Anderson Cancer Center and 293 cases from the Mayo Clinic. We then performed a two-pronged validation of the top 25 variants that included additional validation in 1,256 NSCLC patients from Taiwan and assessment of expression quantitative trait loci (eQTL) and differential expression of genes surrounding the top loci in 70 tumors and matched normal tissues. A total of 94 loci were significant for overall survival in both MD Anderson and Mayo studies in the consistency meta-analysis phase, with the top 25 variants reaching a p-value of 10−6. Two variants of these 25 were also significant in the Taiwanese population: rs6901416 (HR:1.44, 95%CI:1.01-2.06) and rs10766739 (HR:1.23, 95%CI:1.00-1.51). These loci resulted in a reduction in median survival time of at least 8 and 5 months in three populations, respectively. An additional six variants (rs4237904, rs7976914, rs4970833, rs954785, rs485411, and rs10906104) were validated through eQTL analysis that identified significant correlations with expression levels of six genes (LEMD3, TMBIM, ATXN7L2, SHE, ITIH2, and NUDT5, respectively) in normal lung tissue. These genes were also significantly differentially expressed between the tumor and normal lung. These findings identify several novel, candidate prognostic markers for NSCLC in never smokers, with eQTL analysis suggesting a potential biological mechanism for a subset of these observed associations.

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Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study of Genetic Predictors of Overall Survival for Non–Small Cell Lung Cancer in Never Smokers

Wang

et al. 2013

Cancer Research

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“…Heavy chains are transferred from chondroitin sulfate of IαI onto HA, with TSG-6 as a catalyst and co-factor [64,65]. Elevated SHAP-HA complex levels are found in the serum of cancer patients [66]. TSG-6 is also reported to bind to HA as oligomers, and to form complexes with pentraxin [67] and thrombospondin [68], bringing several HA molecules together.…”

Section: The Ha Interactome In Cancermentioning

confidence: 99%

Therapeutic Targeting of Hyaluronan in the Tumor Stroma

Kultti

Jiang

et al. 2012

Cancers

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The tumor stroma, consisting of non-malignant cells and the extracellular matrix, undergoes significant quantitative and qualitative changes throughout malignant transformation and tumor progression. With increasing recognition of the role of the tumor microenvironment in disease progression, stromal components of the tumor have become attractive targets for therapeutic intervention. Stromal accumulation of the glycosaminoglycan hyaluronan occurs in many tumor types and is frequently associated with a negative disease prognosis. Hyaluronan interacts with other extracellular molecules as well as cellular receptors to form a complex interaction network influencing physicochemical properties, signal transduction, and biological behavior of cancer cells. In preclinical animal models, enzymatic removal of hyaluronan is associated with remodeling of the tumor stroma, reduction of tumor interstitial fluid pressure, expansion of tumor blood vessels and facilitated delivery of chemotherapy. This leads to inhibition of tumor growth and increased survival. Current evidence shows that abnormal accumulation of hyaluronan may be an important stromal target for cancer therapy. In this review we highlight the role of hyaluronan and hyaluronan-mediated interactions in cancer, and discuss historical and recent data on hyaluronidase-based therapies and the effect of hyaluronan removal on tumor growth.

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“…Elevated serum levels of the SHAP-HA complex indicate poor prognosis in endometrial and ovarian cancers. [ 49 , 50 ] VCAN plays a role in intercellular signaling and in connecting cells with the ECM. It was reported that VCAN significantly increased in superficial spreading melanoma tissue and metastatic melanoma cell lines.…”

Section: Discussionmentioning

confidence: 99%

Screening and identification of key genes and pathways in metastatic uveal melanoma based on gene expression using bioinformatic analysis

Xie¹,

Wu²,

et al. 2020

Medicine

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The current study aimed to elucidate the molecular mechanisms and identify the potential key genes and pathways for metastatic uveal melanoma (UM) using bioinformatics analysis. Gene expression microarray data from GSE39717 included 39 primary UM tissue samples and 2 metastatic UM tissue samples. Differentially expressed genes (DEGs) were generated using Gene Expression Omnibus 2R. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the online Database for Annotation, Visualization and Integrated Discovery (DAVID) tool. The web-based STRING tool was adopted to construct a protein--protein interaction (PPI) network. The MCODE tool in Cytoscape was used to generate significant modules of the PPI network. A total of 213 DEGs were identified. GO and KEGG analyses revealed that the upregulated genes were mainly enriched in extracellular matrix organization and blood coagulation cascades, while the downregulated DEGs were mainly related to protein binding, negative regulation of ERK cascade, nucleus and chromatin modification, and lung and renal cell carcinoma. The most significant module was extracted from the PPI network. GO and KEGG enrichment analyses of the module revealed that the genes were mainly enriched in the extracellular region and space organization, blood coagulation process, and PI3K-Akt signaling pathway. Hub genes, including FN1, APOB, F2, SERPINC1, SERPINA1, APOA1, FGG, PROC, ITIH2, VCAN, TFPI, CXCL8, CDH2 , and HP, were identified from DEGs. Survival analysis and hierarchical clustering results revealed that most of the hub genes were associated with prognosis and clinical progression. Results of this bioinformatics analysis may provide predictive biomarkers and potential candidate therapeutic targets for individuals with metastatic UM.

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Clinicopathological Role of Serum-Derived Hyaluronan-Associated Protein (SHAP)-Hyaluronan Complex in Endometrial Cancer

Cited by 6 publications

References 37 publications

Genome-Wide Association Study of Genetic Predictors of Overall Survival for Non–Small Cell Lung Cancer in Never Smokers

Genome-Wide Association Study of Genetic Predictors of Overall Survival for Non–Small Cell Lung Cancer in Never Smokers

Therapeutic Targeting of Hyaluronan in the Tumor Stroma

Screening and identification of key genes and pathways in metastatic uveal melanoma based on gene expression using bioinformatic analysis

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