Overexpression of the c-Met/HGF receptor and its prognostic significance in uterine cervix carcinomas

Baykal, Cem; Al, Ragip Atakan; Yüce, K.; Ayhan, Ali̇

doi:10.1016/s0090-8258(02)00073-2

Cited by 74 publications

(66 citation statements)

References 37 publications

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“…They have all been reported to be related to either cervical tumorigenesis or its progression. [15][16][17][18][19][20][21][22][23][24][25] Further clarification of their functional role in cervical malignancy would be warranted. Six previously FIGURE 6 -Potential signaling pathways involved in cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

Genome‐wide gene expression profiling of cervical cancer in Hong Kong women by oligonucleotide microarray

Wong

Cheung

Tsao

et al. 2006

Intl Journal of Cancer

107

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An analysis of gene expression profiles obtained from cervical cancers was performed to find those genes most aberrantly expressed. Total RNA was prepared from 29 samples of cervical squamous cell carcinoma and 18 control samples, and hybridized to Affymetrix oligonucleotide microarrays with probe sets complementary to over 20,000 transcripts. Unsupervised hierarchical clustering of the expression data readily distinguished normal cervix from cancer. Supervised analysis of gene expression data identified 98 and 139 genes that exhibited >2-fold upregulation and >2-fold downregulation, respectively, in cervical cancer compared to normal cervix. Several of the genes that were differentially regulated included SPP1 (Osteopontin), CDKN2A (p16), RPL39L, Clorf1, MAL, p11, ARS and NICE-1. These were validated by quantitative RT-PCR on an independent set of cancer and control specimens. Gene Ontology analysis showed that the list of differentially expressed genes included ones that were involved in multiple biological processes, including cell proliferation, cell cycle and protein catabolism. Immunohistochemical staining of cancer specimens further confirmed differential expression of SPP1 in cervical cancer cells vs. nontumor cells. In addition, 2 genes, CTGF and RGS1 were found to be upregulated in late stage cancer compared to early stage cancer, suggesting that they might be involved in cancer progression. The pathway analysis of expression data showed that the SPP1, VEGF, CDC2 and CKS2 genes were coordinately differentially regulated between cancer and normal. The present study is promising and provides potential new insights into the extent of expression differences underlying the development and progression of cervical squamous cell cancer. This study has also revealed several genes that may be highly attractive candidate molecular markers/targets for cervical cancer diagnosis, prognosis and therapy. ' 2005 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Genome‐wide gene expression profiling of cervical cancer in Hong Kong women by oligonucleotide microarray

Wong

Cheung

Tsao

et al. 2006

Intl Journal of Cancer

107

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“…In cervical cancer, the prognostic value of the HGF receptor was clarified by Baykal et al (46), therefore, in addition to these traditional prognostic indicators, including FIGO stage and pelvic lymph node metastasis, the pre-treatment serum levels of HGF may be a predictor of tumor progression in certain early stage cervical carcinomas.…”

Section: ------------------------------------------------------------mentioning

confidence: 99%

Expression of growth-regulated oncogene-1, hepatocyte growth factor, platelet-derived growth factor-AA and soluble E-selectin and their association with high-risk human papillomavirus infection in squamous cell carcinoma of the uterine cervix

Zhang

Yang

et al. 2014

Molecular Medicine Reports

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Abstract. The aim of the present study was to evaluate the clinical significance and prognostic value of growth-regulated oncogene-1 (GRO-1), hepatocyte growth factor (HGF), platelet-derived growth factor-AA (PDGF-AA), soluble E-selectin (sE-selectin) and high-risk human papillomavirus (HPV; types 16, 18/45, 31 and 33/52/58/67) infection in cervical squamous cell carcinoma (CSCC). A total of 426 cases were enrolled in the present study, of which 292 cases were patients with CSCC, 43 were patients with cervical intraepithelial neoplasia (CIN) and 91 were healthy controls. Luminex xMAP technology was used to detect the serum levels of GRO-1, HGF, PDGF-AA and sE-selectin in all cases and two-channel fluorescence quantitative polymerase chain reaction was used to determine HPV DNA in cervical scrapings from CSCC and CIN patients. The results demonstrated that the serum levels of GRO-1, HGF and sE-selectin were significantly higher in patients with CSCC compared with patients with CIN and the healthy controls (P<0.0001). Compared with the CIN patients, the HPV positive rate in the CSCC patients significantly increased (P= 0.013). The four factors were correlated with certain clinicopathological variables of CSCC patients to a certain degree (P<0.05) and the levels of HGF were closely associated with HPV infection (P= 0.039). The receiver operating characteristic curves demonstrated that HGF obtained the highest diagnostic value compared with the other three factors. Multivariate Cox regression analysis demonstrated that the serum levels of HGF (P<0.0001), FIGO stage (P<0.0001) and pelvic lymph node metastasis (P=0.001) were independent prognostic factors in patients with CSCC, while high-risk HPV infection did not show any significance in this analysis. These results demonstrated that HGF may be a useful prognostic biomarker rather than high-risk HPV types in patients with CSCC.

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“…Met gene amplification has been found in gastric and colorectal tumors (14)(15)(16)(17) and was recently proposed as a mechanism for acquired resistance to epidermal growth factor receptor inhibitors in lung cancer (18,19). Clinically, overexpression and/ or dysregulation of Met and/or HGF correlates with a poor prognostic outcome in patients with a diverse array of malignancies (20)(21)(22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Tumor Cell Growth, Invasion, and Metastasis by EXEL-2880 (XL880, GSK1363089), a Novel Inhibitor of HGF and VEGF Receptor Tyrosine Kinases

et al. 2009

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Overexpression of the c-Met/HGF receptor and its prognostic significance in uterine cervix carcinomas

Cited by 74 publications

References 37 publications

Genome‐wide gene expression profiling of cervical cancer in Hong Kong women by oligonucleotide microarray

Genome‐wide gene expression profiling of cervical cancer in Hong Kong women by oligonucleotide microarray

Expression of growth-regulated oncogene-1, hepatocyte growth factor, platelet-derived growth factor-AA and soluble E-selectin and their association with high-risk human papillomavirus infection in squamous cell carcinoma of the uterine cervix

Inhibition of Tumor Cell Growth, Invasion, and Metastasis by EXEL-2880 (XL880, GSK1363089), a Novel Inhibitor of HGF and VEGF Receptor Tyrosine Kinases

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