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Laminin C1 expression by uterine carcinoma cells is associated with tumor progression.

ABSTRACT: Molecular markers associated with tumor progression in uterine carcinoma are poorly defined. In this study, we determine whether upregulation of LAMC1, a gene encoding extracellular matrix protein, laminin ?1, is associated with various uterine carcinoma subtypes and stages of tumor progression.An analysis of the immunostaining patterns of laminin ?1 in normal endometrium, atypical hyperplasia, and a total of 150 uterine carcinomas, including low-grade and high-grade endometrioid carcinomas, uterine serous and clear cell carcinoma, was performed. Clinicopathological correlation was performed to determine biological significance. The Cancer Genome Atlas (TCGA) data set was used to validate our results.As compared to normal proliferative and secretory endometrium, for which laminin ?1 immunoreactivity was almost undetectable, increasing laminin C1 staining intensity was observed in epithelial cells from atypical hyperplasia to low-grade endometrioid to high-grade endometrioid carcinoma, respectively. Laminin ?1 expression was significantly associated with FIGO stage, myometrial invasion, cervical/adnexal involvement, angiolymphatic invasion and lymph node metastasis. Similarly, analysis of the endometrial carcinoma data set from TCGA revealed that LAMC1 transcript levels were higher in high-grade than those in low-grade endometrioid carcinoma. Silencing LAMC1 expression by siRNAs in a high-grade endometrioid carcinoma cell line did not affect its proliferative activity but significantly suppressed cell motility and invasion in vitro.These data suggest that laminin ?1 may contribute to the development and progression of uterine carcinoma, likely through enhancing tumor cell motility and invasion. Laminin ?1 warrants further investigation regarding its role as a biomarker and therapeutic target in uterine carcinoma.

SUBMITTER: Kashima H

PROVIDER: S-EPMC4862403 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Laminin C1 expression by uterine carcinoma cells is associated with tumor progression.

Kashima Hiroyasu H Wu Ren-Chin RC Wang Yihong Y Sinno Abdulrahman K AK Miyamoto Tsutomu T Shiozawa Tanri T Wang Tian-Li TL Fader Amanda N AN Shih Ie-Ming IeM

Gynecologic oncology 20150903 2

<h4>Objectives</h4>Molecular markers associated with tumor progression in uterine carcinoma are poorly defined. In this study, we determine whether upregulation of LAMC1, a gene encoding extracellular matrix protein, laminin γ1, is associated with various uterine carcinoma subtypes and stages of tumor progression.<h4>Methods</h4>An analysis of the immunostaining patterns of laminin γ1 in normal endometrium, atypical hyperplasia, and a total of 150 uterine carcinomas, including low-grade and high ...[more]

PMID: 26343160

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Project description:BackgroundUterine corpus endometrial carcinoma (UCEC) is a common malignant cancer type which affects the health of women worldwide. However, its molecular mechanism has not been elucidated.MethodsTo identify the hub modules and genes in UCEC associated with clinical phenotypes, the RNA sequencing data and clinical data of 543 UCEC samples were obtained from The Cancer Genome Atlas (TCGA) database and then subjected to weighted gene co-expression network analysis (WGCNA). To explore the potential biological function of the hub modules, Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted. Genes differentially expressed in UCEC were screened according to TCGA data using the "gdcDEAnalysis" package in R (The R Foundation for Statistical Computing). After intersecting with hub genes, the shared genes were used for further survival analyses. The relationship between gene expression level and clinical phenotype was analyzed in the TCGA-UCEC cohort in The University of ALabama at Birmingham CANcer data analysis Portal and the Human Protein Atlas. The microarray data set GSE17025 was also analyzed to validate the gene expression profiles.ResultsThere were 19 coexpression modules generated by WGCNA. Among them, 2 modules with 198 hub genes were highly correlated with clinical features (especially histologic grade and clinical stage). Meanwhile, 4,003 differentially expressed genes (DEGs) were screened out, and 164 DEGs overlapped with hub genes. Survival analyses revealed that high expression of GINS4 and low expression of ESR1 showed a trend of poor prognosis. Further analyses demonstrated that both messenger RNA (mRNA) and protein expression profiles of GINS4 and ESR1 were significantly associated with UCEC development and progression in TCGA and GSE17025 cohorts.ConclusionsBased on the integrated bioinformatic analyses, our data indicated that GINS4 and ESR1 might serve as potential prognostic markers and targets for UCEC therapy.

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Laminin C1 expression by uterine carcinoma cells is associated with tumor progression.

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Laminin C1 expression by uterine carcinoma cells is associated with tumor progression.

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