Dataset Information

Hedgehog Interacting Protein 1 is a Prognostic Marker and Suppresses Cell Metastasis in Gastric Cancer.

ABSTRACT: Background: The gene Hedgehog interacting protein (HHIP) is a pivotal morphogen for multiple developmental processes. However, the expression and clinical correlation of HHIP in gastric cancer (GC) has not been fully investigated. Here, we aimed to explore the expression of HHIP in gastric cancer (GC) and evaluate its clinicopathological and functional correlations. Methods: The expression of HHIP mRNA was first determined in the Human Protein Atlas (HPA) and The Cancer Genome Atlas (TCGA) GC database and then validated by RT-qPCR (n = 41) and immunohistochemistry (IHC, n = 95) in a cohort of in-house GC patients and in 29 cases of gastric intraepithelial neoplasia (GIN). The clinicopathological and functional relationship of HHIP with GC were also analyzed. Results: We found that HHIP mRNA were significantly downregulated in GC in the TCGA and HPA databases, as well as in our in-house cohort (P < 0.05). HHIP mRNA is mainly located in the cell nucleus, while HHIP protein is mainly located in the cell cytoplasm. Moreover, the HHIP protein level in the GIN tissues was significantly higher than that in the GC tissues (P < 0.001) and significantly lower than that in adjacent normal controls (P < 0.001). In addition, low HHIP expression was correlated with lymphatic metastasis (P = 0.041), pTNM stage (P = 0.007) and nervous system invasion (P = 0.001). Furthermore, we observed strong positive correlations between HHIP protein expression and overall survival (P < 0.001) and disease-free survival (P = 0.027) in GC patients. HHIP protein expression was an independent prognostic factor for overall survival (P < 0.001). Functional experimental results showed that overexpression of HHIP attenuated the migration and invasion ability of GC cells (P < 0.01). Conclusion: HHIP may be a promising tumor metastatic-suppressor and prognostic biomarker for gastric cancer.

SUBMITTER: Sun H

PROVIDER: S-EPMC6299386 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Hedgehog Interacting Protein 1 is a Prognostic Marker and Suppresses Cell Metastasis in Gastric Cancer.

Sun Hui H Ni Shu Juan SJ Ye Min M Weng Weiwei W Zhang Qiongyan Q Zhang Meng M Tan Cong C Wang Lei L Huang Dan D Du Xiang X Xu Midie M Sheng Weiqi W

Journal of Cancer 20181124 24

<b>Background</b>: The gene Hedgehog interacting protein (HHIP) is a pivotal morphogen for multiple developmental processes. However, the expression and clinical correlation of HHIP in gastric cancer (GC) has not been fully investigated. Here, we aimed to explore the expression of HHIP in gastric cancer (GC) and evaluate its clinicopathological and functional correlations. <b>Methods</b>: The expression of HHIP mRNA was first determined in the Human Protein Atlas (HPA) and The Cancer Genome Atla ...[more]

PMID: 30588248

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Project description:AimTo evaluate the potential of thioredoxin (TXN) and thioredoxin-interacting protein (TXNIP) expression as biomarkers for predicting gastric cancer recurrence.MethodsTXN and TXNIP expression levels were acquired from gene expression microarray data for 65 human gastric cancer tissues. We determined whether each gene expression level was associated with cancer recurrence and investigated the relationship between the two genes. For validation, the expression levels of TXN and TXNIP were measured by quantitative real-time reverse transcription polymerase chain reaction in 68 independent stage III gastric cancer patients. The correlation between gene expression and cancer prognosis was evaluated. Immunohistochemical staining was performed to investigate the protein expression levels of TXN and TXNIP and to characterize the expression patterns of each protein.ResultsTXN was a prognosis-related gene (P = 0.009), whereas TXNIP, a TXN inhibitor, demonstrated a negative correlation with TXN in the gene expression microarray data. In the 68 stage III patients, the expression levels of both TXN and TXNIP had a statistically significant effect on recurrence-free survival (RFS, P = 0.008 and P = 0.036, respectively). The low TXN and high TXNIP expression group exhibited a better prognosis than the other groups, and the high TXN and low TXNIP expression group exhibited a poorer prognosis (P < 0.001 for RFS and P = 0.001 for overall survival). More than half of the patients in the simultaneously high TXN and low TXNIP expression group experienced a recurrence within 1 year after curative surgery, and the 5-year survival rate of the patients in this group was 29%, compared with 89% in the low TXN and high TXNIP expression group. The TXN protein was overexpressed in 65% of the gastric cancer tissues, whereas the TXNIP protein was underexpressed in 85% of the cancer cells. In a correlation analysis, TXN and TXNIP were highly correlated with many oncogenes and tumor suppressors as well as with genes related to energy, protein synthesis and autophagy.ConclusionTXN and TXNIP are promising prognostic markers for gastric cancer, and performing personalized adjuvant treatment based on TXN and TXNIP expression levels would be an effective practice in the treatment of gastric cancer.

Project description:Deregulation of microRNAs (miRs) contributes to progression and metastasis of prostate and other cancers. miR-23b and -27b, encoded in the same miR cluster (miR-23b/-27b), are downregulated in human metastatic prostate cancer compared with primary tumors and benign tissue. Expression of miR-23b/-27b decreases prostate cancer cell migration, invasion and results in anoikis resistance. Conversely, antagomiR-mediated miR-23b and -27b silencing produces the opposite result in a more indolent prostate cancer cell line. However, neither miR-23b/-27b expression or inhibition impacts prostate cancer cell proliferation suggesting that miR-23b/-27b selectively suppresses metastasis. To examine the effects of miR-23b/-27b on prostate cancer metastasis in vivo, orthotopic prostate xenografts were established using aggressive prostate cancer cells transduced with miR-23b/-27b or non-targeting control miRNA. Although primary tumor formation was similar between miR-23b/-27b-transduced cells and controls, miR-23b/-27b expression in prostate cancer cells decreased seminal vesicle invasion and distant metastases. Gene-expression profiling identified the endocytic adaptor, Huntingtin-interacting protein 1-related (HIP1R) as being downregulated by miR-23b/-27b. Increased HIP1R expression in prostate cancer cells inversely phenocopied the effects of miR-23b/-27b overexpression on migration, invasion and anchorage-independent growth. HIP1R rescued miR-23b/-27b-mediated repression of migration in prostate cancer cells. HIP1R mRNA levels were decreased in seminal vesicle tissue from mice bearing miR-23b/-27b-transduced prostate cancer cell xenografts compared with scrambled controls, suggesting HIP1R is a key functional target of miR-23b/-27b. In addition, depletion of HIP1R led to a more rounded, less mesenchymal-like cell morphology, consistent with decreased metastatic properties. Together, these data demonstrate that the miR-23b/-27b cluster functions as a metastasis-suppressor by decreasing HIP1R levels in pre-clinical models of prostate cancer.

Dataset Information

Hedgehog Interacting Protein 1 is a Prognostic Marker and Suppresses Cell Metastasis in Gastric Cancer.

Publications

Hedgehog Interacting Protein 1 is a Prognostic Marker and Suppresses Cell Metastasis in Gastric Cancer.

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