LyGDI is a Promising Biomarker for Ovarian Cancer

Zhen, Hongying; Yang, Shaomin; Wu, Hongpeng; Wang, Shuling; Lv, Jingqiao; Ma, Lijun; Zhang, Xiaowei

doi:10.1111/igc.0b013e3181d0b02d

Cited by 11 publications

(8 citation statements)

References 26 publications

(27 reference statements)

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“…9 To date, there has been very limited analyses of RhoGDI2 protein expression in ovarian cancer and no studies of functional relevance. 15,16,25 Our RhoGDI2 shRNA suppression studies in the HeyA8 ovarian carcinoma cell line demonstrated that suppression of RhoGDI2 expression was associated with increased anchorageindependent growth, Matrigel invasion and lung colony metastatic tumor formation. However, our IHC analyses found that RhoGDI2 was significantly overexpressed in high-grade compared with low-grade ovarian cancers, that RhoGDI2 expression correlated with histological subtype of cancer, and no statistically significant association with survival.…”

Section: Discussionmentioning

confidence: 91%

RhoGDI2 antagonizes ovarian carcinoma growth, invasion and metastasis

et al. 2011

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Previous studies described functional roles for Rho GDP dissociation inhibitor 2 (RhoGDI2) in bladder, gastric and breast cancers. however, only limited expression and no functional analyses have been done for RhoGDI2 in ovarian cancer. We determined RhoGDI2 protein expression and function in ovarian cancer. First, protein gel blot analysis was performed to determine the expression levels of RhoGDI2 in ovarian cells lines. RhoGDI2 but not RhoGDI1 protein expression levels varied widely in ovarian carcinoma cell lines, with elevated levels seen in Ras-transformed ovarian epithelial cells. Next, immunohistochemistry was performed to detect RhoGDI2 expression in patient samples of ovarian cysts and ovarian cancer with known histological subtype, stage, grade and outcome. RhoGDI2 protein was significantly overexpressed in high-grade compared with low-grade ovarian cancers, correlated with histological subtype, and did not correlate with stage of ovarian cancer nor between carcinomas and benign cysts. Unexpectedly, stable suppression of RhoGDI2 protein expression in heyA8 ovarian cancer cells increased anchorage-independent growth and Matrigel invasion in vitro and in tail-vein lung colony metastatic growth in vivo. Finally, we found that RhoGDI2 stably-associated preferentially with Rac1 and suppression of RhoGDI2 expression resulted in decreased Rac1 activity and Rac-associated JNK and p38 mitogenactivated protein kinase signaling. RhoGDI2 antagonizes the invasive and metastatic phenotype of heyA8 ovarian cancer cells. In summary, our results suggest significant cell context differences in RhoGDI2 function in cancer cell growth. RhoGDI2 antagonizes ovarian carcinoma growth, invasion and metastasis

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Section: Discussionmentioning

confidence: 91%

RhoGDI2 antagonizes ovarian carcinoma growth, invasion and metastasis

et al. 2011

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“…Alternative methods are being developed for patients who have normal CA-125 levels but are suspected to having recurrent disease based on clinical symptoms [5]. These methods include other potential biomarkers, the most promising being human epydidimus protein 4 (HE4), [6], [7], [8], [9], [10] despite detection rates of 50–60% in early stage ovarian cancer. A comprehensive study comparing the sensitivity of ovarian cancer biomarkers to discriminate between benign and malignant masses has been described [11] as well as the role of molecular markers in prognosis and therapy reviewed in [12].…”

Section: Introductionmentioning

confidence: 99%

Identification of Metabolites in the Normal Ovary and Their Transformation in Primary and Metastatic Ovarian Cancer

2011

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In this study, we characterized the metabolome of the human ovary and identified metabolic alternations that coincide with primary epithelial ovarian cancer (EOC) and metastatic tumors resulting from primary ovarian cancer (MOC) using three analytical platforms: gas chromatography mass spectrometry (GC/MS) and liquid chromatography tandem mass spectrometry (LC/MS/MS) using buffer systems and instrument settings to catalog positive or negative ions. The human ovarian metabolome was found to contain 364 biochemicals and upon transformation of the ovary caused changes in energy utilization, altering metabolites associated with glycolysis and β-oxidation of fatty acids—such as carnitine (1.79 fold in EOC, p<0.001; 1.88 fold in MOC, p<0.001), acetylcarnitine (1.75 fold in EOC, p<0.001; 2.39 fold in MOC, p<0.001), and butyrylcarnitine (3.62 fold, p<0.0094 in EOC; 7.88 fold, p<0.001 in MOC). There were also significant changes in phenylalanine catabolism marked by increases in phenylpyruvate (4.21 fold; p = 0.0098) and phenyllactate (195.45 fold; p<0.0023) in EOC. Ovarian cancer also displayed an enhanced oxidative stress response as indicated by increases in 2-aminobutyrate in EOC (1.46 fold, p = 0.0316) and in MOC (2.25 fold, p<0.001) and several isoforms of tocopherols. We have also identified novel metabolites in the ovary, specifically N-acetylasparate and N-acetyl-aspartyl-glutamate, whose role in ovarian physiology has yet to be determined. These data enhance our understanding of the diverse biochemistry of the human ovary and demonstrate metabolic alterations upon transformation. Furthermore, metabolites with significant changes between groups provide insight into biochemical consequences of transformation and are candidate biomarkers of ovarian oncogenesis. Validation studies are warranted to determine whether these compounds have clinical utility in the diagnosis or clinical management of ovarian cancer patients.

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“…Other specific patient cohort studies showed interesting results in which ovarian endometrioma and pelvic inflammatory disease were associated with ovarian cancer risk (Kobayashi et al, 2007;Lin et al, 2011), but they were insufficient in terms of how they controlled confounding factors, as these were also based on hospital records or health insurance claims data. Among these previous studies, only four considered the differences among cancer cases, benign tumor cases and controls (Kim et al, 2009;Xie et al, 2004;Zhen et al, 2010;Zou et al, 2010). Moreover, they all had small sample sizes that were under 150.…”

Section: Discussionmentioning

confidence: 99%

Korean Epithelial Ovarian Cancer Study (Ko-EVE): Protocols and Interim Report

Hyun¹,

Kim²,

Choi³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Background: There have been few studies of Asian ovarian cancer and benign tumors. The primary aim of this paper was to report the protocol of the Ko-EVE study to examine epidemiological and molecular factors for ovarian cancer and benign neoplasms and to ascertain the major risk factors for ovarian cancer control in Korea. Methods: This case-control study covers incident epithelial ovarian cancers and benign neoplasms, four major centers participating in enrolling incident cases and 3 hospitals enrolling healthy controls among health examinees. Standardized questionnaires were administered by trained interviewers, including sections on socio-demographics characteristics, past medical history, medication usage, family history, lifetime consumption of alcohol and tobacco, diet, physical activity, and reproductive factors for women. Various biological specimens were collected in the biorepository according to the standardized protocol. Annual follow-up for cancer cases and follow-up at the 1st year for benign tumor cases are performing to evaluate treatment effect and progression. Passive follow to see long-term survival will be conducting using record linkage with national data. Results: The total number recruited in 2010-2011 was 246 epithelial ovarian cancer cases, 362 benign epithelial tumors and 345 controls. We are planning to collect subjects for at least 1,500 sets of ovarian cancer, 2,000 benign tumors and 1,500 controls till 2018. Conclusion: The Ko-EVE will provide unique and important data to probe the etiology and natural history of Korean epithelial ovarian cancer. It will be continued by genomic and proteomic epidemiological analyses and future intervention studies for the prevention of ovarian cancer among Koreans.

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LyGDI is a Promising Biomarker for Ovarian Cancer

Abstract: These results suggest that LyGDI has significant potential as a marker for detection of ovarian cancer in the patients with ovarian enlargement, including detection of early-stage cancers.

Cited by 11 publications

References 26 publications

RhoGDI2 antagonizes ovarian carcinoma growth, invasion and metastasis

RhoGDI2 antagonizes ovarian carcinoma growth, invasion and metastasis

Identification of Metabolites in the Normal Ovary and Their Transformation in Primary and Metastatic Ovarian Cancer

Korean Epithelial Ovarian Cancer Study (Ko-EVE): Protocols and Interim Report

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