Identification of genes associated with ovarian cancer metastasis using microarray expression analysis

Although the transition from early- to advanced-stage ovarian cancer is a critical determinant of survival, little is known about the molecular underpinnings of ovarian metastasis. We hypothesize that microarray analysis of global gene expression patterns in primary ovarian cancer and metastatic omental implants can identify genes that underlie the metastatic process in epithelial ovarian cancer. We utilized Affymetrix U95Av2 microarrays to characterize the molecular alterations that underlie omental metastasis from 47 epithelial ovarian cancer samples collected from multiple sites in 20 patients undergoing primary surgical cytoreduction for advanced-stage (IIIC/IV) serous ovarian cancer. Fifty-six genes demonstrated differential expression between ovarian and omental samples (P < 0.01), and twenty of these 56 differentially expressed genes have previously been implicated in metastasis, cell motility, or cytoskeletal function. Ten of the 56 genes are involved in p53 gene pathways. A Bayesian statistical tree analysis was used to identify a 27-gene expression pattern that could accurately predict the site of tumor (ovary versus omentum). This predictive model was evaluated using an external data set. Nine of the 27 predictive genes have previously been shown to be involved in oncogenesis and/or metastasis, and 10/27 genes have been implicated in p53 pathways. Microarray findings were validated by real-time quantitative PCR. We conclude that gene expression patterns that distinguish omental metastasis from primary epithelial ovarian cancer can be identified and that many of the genes have functions that are biologically consistent with a role in oncogenesis, metastasis, and p53 gene networks.     

Characterization of differentially expressed genes in ovarian cancer by cDNA microarrays

The molecular events leading to the development and progression of ovarian carcinoma are not completely understood. We performed a large-scale survey for the identification of differentially expressed genes between ovarian carcinoma and normal ovarian tissue by using cDNA microarray analysis. We utilized 512 member human novel putative oncogene and tumor suppressor gene cDNA microarrays to study the differences in gene expression between ovarian carcinoma and normal ovarian tissues. Some differentially expressed genes have been further confirmed by immunohistochemical analysis. A total of 39 differentially expressed genes were identified, of which 16 and 23 were specifically expressed in ovarian cancer and normal ovarian tissue, respectively. The comparison of average signal of differentially expressed genes exhibited at least a twofold difference in expression. The differentially expressed genes may be related to the carcinogenesis and progression of the malignant growth. The use of cDNA microarrays allows simultaneous monitor of the expression of many genes, thereby it speeds up the identification of differentially expressed genes. It is essential for further exploration of the mechanisms of the disease.     

应用抑制性消减杂交筛选卵巢癌紫杉醇耐药差异表达基因

目的:应用抑制性消减杂交技术研究人卵巢癌紫杉醇耐药细胞株OC3/Tax300与其亲本细胞OC3(敏感株)之间基因表达的差异,筛选耐药相关基因,探讨基因表达差异与卵巢癌耐药的相关性。方法:以卵巢癌紫杉醇耐药细胞株OC3/Tax300 mRNA为检测子(tester),以其亲本细胞OC3(敏感株)mRNA为驱赶子(driver),构建cDNA消减文库。随机挑取文库克隆测序,所得结果在GenBank中做同源性比较分析。结果:成功构建了卵巢癌紫杉醇耐药细胞株的特异性cDNA消减文库。从文库中选取阳性克隆,其中76个测序成功,再随机选取36个序列与GenBank数据库进行初步比对,8个可能为新基因,1个为蛋白序列,另27个来源于16个已知基因,这些差异表达基因主要涉及细胞代谢、信号转导、细胞骨架、凋亡、蛋白翻译合成、发育等相关基因。结论:部分基因表达差异与卵巢癌紫杉醇耐药有关。     

A prospective, randomized trial of integrative medicine for women with ovarian cancer

Objectives

Despite increased use of integrative medicine in cancer therapy, little data exist on its efficacy. This prospective, randomized, pilot trial sought to evaluate the feasibility of combined modality integrative medicine (CM-IM) in women with ovarian cancer (OvCA) and evaluate its effects on quality of life (QoL), chemotherapy toxicity and immunologic profiles.

Methods

Women with newly diagnosed OvCA requiring chemotherapy were offered enrollment. Those randomized to the experimental arm received hypnosis, therapeutic massage and healing touch with each cycle of chemotherapy. The control arm received chemotherapy without CM-IM. All patients completed QoL questionnaires prior to cycles 1, 3 and 6, and 6-months after chemotherapy. Immunologic profiles were measured. Statistical analysis was based on intent-to-treat. Student's t-test and Fischer's exact-test were used to determine differences.

Results

Forty-three women enrolled. All women randomized to CM-IM were successfully treated. There were no statistical differences between the groups in age, stage, grade, histologic cell type, CA125 levels, or surgical cytoreductive status. There was no difference in overall QoL measurements. Re-hospitalization rates, treatment delays, anti-emetic use, and infection rates were similar. Immunologic profiles revealed no difference between arms for WBC or salivary IgA levels. Women receiving CM-IM had consistently higher levels of CD4, CD8 and NK cells, although this did not reach statistical significance.

Conclusions

Prospective clinical evaluation of integrative medicine for women with gynecologic malignancy is feasible. This first, pilot study of CM-IM in gynecologic oncology demonstrated no improvement in QoL or chemotherapy toxicity. Integrative medicine-associated improvements in immunologic profiles warrant further investigation.     

卵巢癌相关基因筛选的初步研究

目的 通过研究人卵巢癌组织和正常卵巢组织中差异表达的基因，筛选出卵巢癌相关基因以用于早期诊断和治疗。方法 以cDNA基因表达谱芯片分析研究卵巢组织样本和正常卵巢组织的基因表达谱，计算机分析后比较两种组织中差异表达的基因。结果 共筛选出差异表达的基因1785条，表达上调基因有40条，下调基因138条，有显著表达差异的基因54条，涉及到11大类基因。结论 卵巢癌同其它恶性肿瘤一样，是多种基因结构和功能改变的结果，有关卵巢癌特异性相关基因及其作用尚有待进一步研究。     

A new prognostic index model using meta-analysis in early-stage epithelial ovarian cancer

Objectives

To construct a novel prognostic index (PI) model of early-stage epithelial ovarian cancer (EOC).

Methods

The PI model was constructed through meta-analyses. The methodological quality of the studies was assessed using the modified Jadad scale for randomized controlled trials (RCTs) and the Newcastle-Ottawa scale for non-RCTs. The prognosis factors of the PI model that had a significant impact on the recurrence-free survival (RFS) of patients with early-stage ovarian cancer were chosen. A total of 177 patients with early-stage ovarian cancer who were treated at Severance Hospital were analyzed using the new PI model to test its utility.

Results

The equation PI = 2 × age + 86 (if grade 2) or 105 (if grade 3) + 53 (if stage Ib or Ic) or 130 (if stage II) + 53 (if no lymphadenectomy) − 43 (for adjuvant chemotherapy of 3 times or more) + 10 (calibrating constant) was derived. Based on PI values, the high-risk group showed a significant 5 year-RFS difference compared to the low-risk group (P-value < 0.01 by log-rank test) and a borderline significance in comparison to the intermediate-risk group (P-value = 0.08). When the cutoff level of PI values was set at 211, the low- and high-risk groups of recurrence within 5 years were also identified by Cox regression analysis (HR = 7.25, 95% CI: 2.98-17.65) .

Conclusions

Our PI model was predictive in this study and may be effective in clinical practice. Further prospective studies should be conducted to confirm the predictive ability of the new PI model for early-stage EOC recurrence.     

机器人手术系统与腹腔镜在卵巢癌手术中应用效果的meta分析

目的:系统评价机器人手术系统在卵巢癌手术中的有效性和安全性。方法:检索Pubmed、Embase、Cochrane Library、Web of Science、CNKI、CBM和万方数据库从建库至2018年5月1日的文献,对所纳入的研究,运用Revman 5.3软件进行meta分析。结果:最终纳入9篇文献,受试患者共404例(机器人组178例,腹腔镜组226例)。Meta分析结果显示,与腹腔镜组相比,机器人手术系统可显著减少术中出血量,在早期卵巢癌手术中手术时间长于腹腔镜组,尚未发现两种手术方式在其他方面的明显差异。结论:在卵巢癌尤其是早期卵巢癌手术中,机器人手术系统在近期疗效上存在一定优势,但其远期疗效仍需进一步研究。     

Low-grade ovarian cancer in an adolescent patient

BACKGROUND: Ovarian tumors in the pediatric population are most likely to be of germ cell origin. However, serous tumors have also been reported in adolescent patients. CASE: A 14-year-old girl was diagnosed with stage IIIc low-grade ovarian cancer. Her serum CA-125 was elevated preoperatively and was a marker for recurrence of disease. Five months after completing standard chemotherapy, she developed recurrent disease, which progressed despite hormonal therapy. She then developed toxicity on liposomal doxorubicin (Doxil) and is now receiving hospice care. CONCLUSION: Low-grade serous adenocarcinoma of the ovary can present as advanced disease and should be considered in the differential diagnosis of an ovarian mass in an adolescent patient.     

Identification of common mechanisms between endometriosis and ovarian cancer

Purpose  

To determine common molecular markers between endometriosis and ovarian cancer.