Expression profiling correlates with treatment response in women with advanced serous epithelial ovarian cancer

Abstract

The majority of epithelial ovarian carcinomas are of serous subtype, with most women presenting at an advanced stage. Approximately 70% respond to initial chemotherapy but eventually relapse. We aimed to find markers of treatment response that might be suitable for routine use, using the gene expression profile of tumor tissue. Thirty one women with histologically-confirmed latestage serous ovarian cancer were classified into 3 groups based on response to treatment (nonresponders, responders with relapse less than 12 months and responders with no relapse within 12 months). Gene expression profiles of these specimens were analyzed with respect to treatment response and survival (minimum 36 months follow-up). Patients' clinical features did not correlate with prognosis, or with specific gene expression patterns of their tumors. However women who did not respond to treatment could be distinguished from those who responded with no relapse within 12 months based on 34 gene transcripts (p < 0.02). Poor prognosis was associated with high expression of inhibitor of differentiation-2 (ID2) (p 5 0.001). High expression of decorin (DCN) and ID2 together was strongly associated with reduced survival (p 5 0.003), with an estimated 7-fold increased risk of dying (95% CI 1.9-29.6; 14 months survival) compared with low expression (44 months). Immunohistochemical analysis revealed both nuclear and cytoplasmic distribution of ID2 in ovarian tumors. High percentage of nuclear staining was associated with poor survival, although not statistically significantly. In conclusion, elevated expression of ID2 and DCN was significantly associated with poor prognosis in a homogeneous group of ovarian cancer patients for whom survival could not be predicted from clinical factors. ' 2006 Wiley-Liss, Inc.Key words: ovarian cancer; expression profiling; prognosis; treatment response; survival Ovarian cancer is the fifth leading cause of cancer death in women in the United States, with approximately 23,000 new cases and 14,000 deaths annually.1 The majority are epithelial ovarian carcinomas of the serous subtype. Most women present at an advanced stage when the disease has spread and, after surgery, platinum-based chemotherapy is the most widely used first-line treatment. Less than 20% of women with advanced cancer do not respond to initial chemotherapy; however, 70% respond initially but become platinum-resistant. Consequently, the 5-year survival for women with advanced disease is only 30%. 1,2Gene expression profiling using microarray technology offers improved classification and outcome prediction in a number of cancers.3-6 Expression profiling of ovarian cancer has identified candidate molecular markers, 7-10 differences between histopathologic subtypes or grades of cancer, 11,12 and patterns associated with suboptimal debulking. 13 A number of studies have evaluated gene expression profiling as a possible predictor of patient survival. Gene expression differences between short-and long-term survivors 14,15 and early relapse (at 21 months)...

Kallikrein-Related Peptidase 7 Promotes Multicellular Aggregation via the α5β1 Integrin Pathway and Paclitaxel Chemoresistance in Serous Epithelial Ovarian Carcinoma

“…Other cell lines were generous gifts from Dr. Nelly Auersperg (University of British Columbia, Vancouver, British Columbia, Canada; IOSE144, IOSE379, and IOSE7576) and Dr. Samuel Mok (Harvard University, Cambridge, MA; HOSE17.1, OVCA420, and OVCA432). Four normal ovarian, 31 serous EOC tissue (22), and 7 EOC RNA (15) samples were described previously. Clinical and pathologic information of EOC patients was obtained from the Royal Brisbane Women's Hospital (Supplementary Table S1).…”

“…The copy number of KLK7-181 was obtained by subtraction of KLK7-253 from total amplified KLK7. Microarray analysis was performed as previously described (22).…”

Overexpressed DNA-binding protein inhibitor 2 as an unfavorable prognosis factor promotes cell proliferation in nasopharyngeal carcinoma

“…On the contrary, there was more evidence indicating that nuclear over-expression of ID2 in cancer cell could promote tumor progression and was not a favorable prognosis factor in prostate cancer [8], non-small cell lung cancer [19], and ovarian cancer, etc. [20]. In this study, attributing to the similar expression level of ID2 in cytoplasm among NPC, atypical hyperplasia, squamous, and normal nasopharynx tissues, we did not evaluate the correlation of cytoplasm ID2 expression with clinical parameters of NPC patients, whereas in nucleus we found that ID2 over-expression was significantly associated with T classification, N classification, and clinical stages of NPC patients.…”

Differential Gene Expression in Glioblastoma Defined by ADC Histogram Analysis: Relationship to Extracellular Matrix Molecules and Survival

“…27 It has also been demonstrated that decorin expression is proportional to the quantity of tumor stroma; in patients with ovarian cancer, high decorin expression is associated with a higher incidence of relapse. 28 Furthermore, a dominant-negative mutation in U87 cells of the ischemic responsive enzyme "inositolrequiring enzyme 1␣" causes a 48-fold increase in decorin gene expression and is associated with a proinvasive and less angiogenic phenotype. 29 We found that increased levels of decorin gene expression levels were associated with shorter survival.…”