Assessment of Hepatocyte Growth Factor in Ovarian Cancer Mortality

Goode, Ellen L.; Chenevix-Trench, Georgia; Hartmann, Lynn C.; Fridley, Brooke L.; Kalli, Kimberly R.; Vierkant, Robert A.; Larson, Melissa C.; White, Kristin L.; Keeney, Gary L.; Oberg, Trynda N.; Cunningham, Julie M.; Beesley, Jonathan; Johnatty, Sharon E.; Chen, Xiaoqing; Goodman, Katelyn E.; Armasu, Sebastian M.; Rider, David N.; Sicotte, Hugues; Schmidt, M.; Elliott, Elaine A.; Høgdall, Estrid; Kjær, Susanne K.; Fasching, Peter A.; Ekici, Arif B.; Lambrechts, Diether; Despierre, Evelyn; Høgdall, Claus; Lundvall, Lene; Karlan, Beth Y.; Gross, Jenny; Brown, Robert E.; Chien, Jeremy; Duggan, David; Tsai, Ya Yu; Phelan, Catherine M.; Kelemen, Linda E.; Peethambaram, Prema P.; Schildkraut, Joellen M.; Shridhar, Vijayalakshmi; Sutphen, Rebecca; Couch, Fergus J.; Sellers, Thomas A.

doi:10.1158/1055-9965.epi-11-0455

Cited by 32 publications

(32 citation statements)

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“…Although an association between the rs1800793 single nucleotide polymorphism and ovarian cancer mortality has been identified, this did not correlate with changes in protein or mRNA expression [29]. However, transcriptional upregulation has been observed resulting from Stat-3 and c-Src expression [60], and the co-expression of HGF and cMET in tumour cells can drive autocrine activation, as well as increased transcription for both genes.…”

Section: Mis-regulation Mechanisms Of Hgf/cmetmentioning

confidence: 95%

“…In recent years, mis-regulation of the HGF/cMET pathway has been investigated in ovarian cancer, and high expression of cMET has been identified in subsets of all four major histotypes of EOC (high grade serous, clear cell, mucinous, and endometrioid [22][23][24][25][26][27][28][29]). It must be noted, however, that the outcome from this over-expression remains unclear.…”

Section: Hgf/cmet In Ovarian Cancermentioning

confidence: 99%

“…It must be noted, however, that the outcome from this over-expression remains unclear. While several studies have demonstrated a correlation between high cMET expression and poor prognosis [25,30], others have shown no statistically significant correlation between cMET expression and shorter survival [26,29], and still others suggest that cMET is expressed in early tumours, and is associated with good prognostic factors [23]. It should be noted that the majority of these studies were performed on relatively small numbers of samples, and usually contained mixed subtypes of EOC, thus further confusing the matter.…”

Section: Hgf/cmet In Ovarian Cancermentioning

confidence: 99%

“…While HGF is typically expressed in the stroma, in ovarian cancer samples, it appears to be expressed in the epithelial cells [29,35,19,32], potentially generating an autocrine loop. However, it has been previously noted that HGF can regulate its own expression [36] as well as that of cMET [37], setting in place an auto-amplification loop, and it is possible that one of the early steps of ovarian carcinogenesis is the coexpression of HGF and cMET in ovarian surface epithelium.…”

Section: Hgf/cmet In Ovarian Cancermentioning

confidence: 99%

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The Therapeutic Potential of Targeting the HGF/cMET Axis in Ovarian Cancer

Moran-Jones

2016

Mol Diagn Ther

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Survival rates for ovarian cancer have remained relatively stable for the past two decades, despite advances in surgical techniques and cytotoxic chemotherapeutics, indicating a requirement for better therapies. One pathway currently proposed for targeting is the HGF/cMET pathway. Up-regulated in a number of tumour types, cMET is a tyrosine kinase receptor expressed on epithelial cells. In ovarian cancer, it has been identified as highly expressed in the four major subtypes, with expression estimates ranging from 11-68% of cases. HGF, the only known ligand for cMET, is found at high levels in both serum and ascites in women with ovarian cancer, and proposed to induce both migration and metastasis. However, clinically validated biomarkers are not yet available for either HGF or cMET, preventing a clear understanding of the true rate of over-expression, or its correlation with prognosis.

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Section: Mis-regulation Mechanisms Of Hgf/cmetmentioning

confidence: 95%

Section: Hgf/cmet In Ovarian Cancermentioning

confidence: 99%

Section: Hgf/cmet In Ovarian Cancermentioning

confidence: 99%

Section: Hgf/cmet In Ovarian Cancermentioning

confidence: 99%

See 2 more Smart Citations

The Therapeutic Potential of Targeting the HGF/cMET Axis in Ovarian Cancer

Moran-Jones

2016

Mol Diagn Ther

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“…Participating studies 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63 …”

Section: Supporting Informationmentioning

confidence: 99%

Association of p16 expression with prognosis varies across ovarian carcinoma histotypes: an Ovarian Tumor Tissue Analysis consortium study

Rambau

Vierkant

Intermaggio

et al. 2018

The Journal of Pathology CR

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We aimed to validate the prognostic association of p16 expression in ovarian high‐grade serous carcinomas (HGSC) and to explore it in other ovarian carcinoma histotypes. p16 protein expression was assessed by clinical‐grade immunohistochemistry in 6525 ovarian carcinomas including 4334 HGSC using tissue microarrays from 24 studies participating in the Ovarian Tumor Tissue Analysis consortium. p16 expression patterns were interpreted as abnormal (either overexpression referred to as block expression or absence) or normal (heterogeneous). CDKN2A (which encodes p16) mRNA expression was also analyzed in a subset (n = 2280) mostly representing HGSC (n = 2010). Association of p16 expression with overall survival (OS) was determined within histotypes as was CDKN2A expression for HGSC only. p16 block expression was most frequent in HGSC (56%) but neither protein nor mRNA expression was associated with OS. However, relative to heterogeneous expression, block expression was associated with shorter OS in endometriosis‐associated carcinomas, clear cell [hazard ratio (HR): 2.02, 95% confidence (CI) 1.47–2.77, p < 0.001] and endometrioid (HR: 1.88, 95% CI 1.30–2.75, p = 0.004), while absence was associated with shorter OS in low‐grade serous carcinomas (HR: 2.95, 95% CI 1.61–5.38, p = 0.001). Absence was most frequent in mucinous carcinoma (50%), and was not associated with OS in this histotype. The prognostic value of p16 expression is histotype‐specific and pattern dependent. We provide definitive evidence against an association of p16 expression with survival in ovarian HGSC as previously suggested. Block expression of p16 in clear cell and endometrioid carcinoma should be further validated as a prognostic marker, and absence in low‐grade serous carcinoma justifies CDK4 inhibition.

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Joint exposure to smoking, excessive weight, and physical inactivity and survival of ovarian cancer patients, evidence from the Ovarian Cancer Association Consortium

Minlikeeva

Cannioto

Jensen

et al. 2019

Cancer Causes Control

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Purpose: Previous epidemiologic studies have shown that smoking, obesity, and physical inactivity are associated with poor survival following a diagnosis of ovarian cancer. Yet, the combined relationship of these unfavorable lifestyle factors on ovarian cancer survival has not been sufficiently investigated. Methods: Using data pooled from 13 studies, we examined the associations between combined exposures to smoking, overweight/obesity weight, and physical inactivity and overall survival (OS) as well as progression-free survival (PFS) among women diagnosed with invasive epithelial ovarian carcinoma (N=7,022). Using age-, stage, and site-adjusted Cox proportional hazards regression models, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) associated with joint exposure to these factors. Results: Combined exposure to current smoking, overweight/obesity, and physical inactivity prior to diagnosis was associated with a significantly increased risk of mortality compared to women who never smoked, had normal body mass index (BMI), and were physically active (HR=1.37; 95% CI=1.10–1.70). The association for a joint exposure to these factors exceeded that of each exposure individually. In fact, exposure to both current smoking and overweight/obesity, and current smoking and physical inactivity was also associated with increased risk of death (HR=1.28; 95 % CI=1.08–1.52, and HR=1.26; 95% CI=1.04–1.54, respectively). The associations were of a similar magnitude when former smoking was assessed in combination with the other exposures and when excessive weight was limited to obesity only. No significant associations were observed between joint exposure to any of these factors and PFS. Conclusions: Joint exposure to smoking, excessive weight, and physical inactivity may negatively impact survival of ovarian cancer patients. These results suggest the importance of examining the combined effect of lifestyle factors on ovarian cancer patients’ survival.

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Assessment of Hepatocyte Growth Factor in Ovarian Cancer Mortality

Cited by 32 publications

References 50 publications

The Therapeutic Potential of Targeting the HGF/cMET Axis in Ovarian Cancer

The Therapeutic Potential of Targeting the HGF/cMET Axis in Ovarian Cancer

Association of p16 expression with prognosis varies across ovarian carcinoma histotypes: an Ovarian Tumor Tissue Analysis consortium study

Joint exposure to smoking, excessive weight, and physical inactivity and survival of ovarian cancer patients, evidence from the Ovarian Cancer Association Consortium

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