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卵巢腺癌的基因组标志物及其与化疗疗效的相关性。

Genomic markers of ovarian adenocarcinoma and its relevancy to the effectiveness of chemotherapy.

作者信息

Englert-Golon Monika, Burchardt Bartosz, Budny Bartlomiej, Dębicki Szymon, Majchrzycka Blanka, Wrotkowska Elzbieta, Jasiński Piotr, Ziemnicka Katarzyna, Słopień Radosław, Ruchała Marek, Sajdak Stefan

机构信息

Surgical Gynecology Clinic of The Gynecological and Obstetrics Clinical Hospital, Poznan University of Medical Sciences, 60-535 Poznan, Poland.

Department of Forensic Sciences, Poznan University of Medical Sciences, 60-535 Poznan, Poland.

出版信息

Oncol Lett. 2017 Sep;14(3):3401-3414. doi: 10.3892/ol.2017.6590. Epub 2017 Jul 17.

DOI:10.3892/ol.2017.6590
PMID:28927094
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5588060/
Abstract

Ovarian cancer is the eighth most common cancer and the seventh highest cause of cancer-associated mortality in women worldwide. It is the second highest cause of mortality among female reproductive malignancies. The current standard first-line treatment for advanced ovarian cancer includes a combination of surgical debulking and standard systemic platinum-based chemotherapy with carboplatin and paclitaxel. Although a deeper understanding of this disease has been attained, relapse occurs in 70% of patients 18 months subsequent to the first-line treatment. Therefore, it is crucial to develop a novel drug that effectively affects ovarian cancer, particularly tumors that are resistant to current chemotherapy. The aim of the present study was to identify genes whose expression may be used to predict survival time or prognosis in ovarian cancer patients treated with chemotherapy. Gene or protein expression is an important issue in chemoresistance and survival prediction in ovarian cancer. In the present study, the research group consisted of patients treated at the Surgical Clinic of the Gynecology and Obstetrics Gynecological Clinical Hospital, Poznan University of Medical Sciences (Poznan, Poland) between May 2006 and November 2014. Additional eligibility criteria were a similar severity (International Federation of Gynecolgy and Obstetrics stage III) at the time of diagnosis, treatment undertaken in accordance with the same schedule, and an extremely good response to treatment or a lack of response to treatment. The performance of the OncoScan assay was evaluated by running the assay on samples obtained from the four patients and by following the recommended protocol outlined in the OncoScan assay manual. The genomic screening using Affymetrix OncoScan Arrays resulted in the identification of large genomic rearrangements across all cancer tissues. In general, chromosome number changes were detected in all examined tissues. The OncoScan arrays enabled the identification of ~100 common somatic mutations. Chemotherapy response in ovarian cancer is extremely complex and challenging to study. The present study identified specific genetic alterations associated with ovarian cancer, but not with response for treatment.

摘要

卵巢癌是全球女性中第八大常见癌症,也是癌症相关死亡的第七大主要原因。它是女性生殖系统恶性肿瘤中第二大致死原因。目前晚期卵巢癌的标准一线治疗包括手术减瘤以及使用卡铂和紫杉醇进行标准的基于铂类的全身化疗。尽管对这种疾病有了更深入的了解,但70%的患者在一线治疗后的18个月会复发。因此,开发一种能有效影响卵巢癌,尤其是对当前化疗耐药的肿瘤的新型药物至关重要。本研究的目的是确定其表达可用于预测接受化疗的卵巢癌患者生存时间或预后的基因。基因或蛋白质表达是卵巢癌化疗耐药和生存预测中的一个重要问题。在本研究中,研究组由2006年5月至2014年11月期间在波兰波兹南医科大学妇产科临床医院外科诊所接受治疗的患者组成。其他入选标准为诊断时严重程度相似(国际妇产科联盟III期)、按照相同方案进行治疗以及对治疗反应极好或无反应。通过对从四名患者获得的样本进行检测并遵循OncoScan检测手册中概述的推荐方案,对OncoScan检测的性能进行了评估。使用Affymetrix OncoScan阵列进行的基因组筛查导致在所有癌组织中鉴定出大量基因组重排。一般来说,在所有检查的组织中都检测到了染色体数目变化。OncoScan阵列能够鉴定出约100个常见的体细胞突变。卵巢癌的化疗反应极其复杂且难以研究。本研究确定了与卵巢癌相关但与治疗反应无关的特定基因改变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d0/5588060/cf030cc0204a/ol-14-03-3401-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d0/5588060/a1d94e5a418e/ol-14-03-3401-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d0/5588060/d67b695e4834/ol-14-03-3401-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d0/5588060/cf030cc0204a/ol-14-03-3401-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d0/5588060/a1d94e5a418e/ol-14-03-3401-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d0/5588060/d67b695e4834/ol-14-03-3401-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d0/5588060/cf030cc0204a/ol-14-03-3401-g02.jpg

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