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假定的癌基因CRNDE是卵巢癌患者的一个负性预后因素。

The putative oncogene, CRNDE, is a negative prognostic factor in ovarian cancer patients.

作者信息

Szafron Lukasz Michal, Balcerak Anna, Grzybowska Ewa Anna, Pienkowska-Grela Barbara, Podgorska Agnieszka, Zub Renata, Olbryt Magdalena, Pamula-Pilat Jolanta, Lisowska Katarzyna M, Grzybowska Ewa, Rubel Tymon, Dansonka-Mieszkowska Agnieszka, Konopka Bozena, Kulesza Magdalena, Lukasik Martyna, Kupryjanczyk Jolanta

机构信息

Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.

Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.

出版信息

Oncotarget. 2015 Dec 22;6(41):43897-910. doi: 10.18632/oncotarget.6016.

Abstract

The CRNDE gene seems to play an oncogenic role in cancers, though its exact function remains unknown. Here, we tried to assess its usefulness as a molecular prognostic marker in ovarian cancer. Based on results of our microarray studies, CRNDE transcripts were further analyzed by Real-Time qPCR-based profiling of their expression. The qPCR study was conducted with the use of personally designed TaqMan assays on 135 frozen tissue sections of ovarian carcinomas from patients treated with platinum compounds and either cyclophosphamide (PC, N = 32) or taxanes (TP, N = 103). Elevated levels of two different CRNDE transcripts were a negative prognostic factor; they increased the risk of death and recurrence in the group of patients treated with TP, but not PC (DNA-damaging agents only). Higher associations were found for overexpression of the short CRNDE splice variant (FJ466686): HR 6.072, 95% CI 1.814-20.32, p = 0.003 (the risk of death); HR 15.53, 95% CI 3.812-63.28, p < 0.001 (the risk of recurrence). Additionally, accumulation of the TP53 protein correlated with decreased expression of both CRNDE transcripts in tumor cells. Our results depict CRNDE as a potential marker of poor prognosis in women with ovarian carcinomas, and suggest that its significance depends on the therapeutic regimen used.

摘要

CRNDE基因似乎在癌症中发挥致癌作用,尽管其确切功能尚不清楚。在此,我们试图评估其作为卵巢癌分子预后标志物的效用。基于我们的微阵列研究结果,通过基于实时定量PCR的表达谱分析对CRNDE转录本进行了进一步分析。使用个人设计的TaqMan检测方法,对135例接受铂类化合物联合环磷酰胺(PC,N = 32)或紫杉烷(TP,N = 103)治疗的卵巢癌患者的冰冻组织切片进行了定量PCR研究。两种不同CRNDE转录本水平升高是一个负面预后因素;它们增加了接受TP治疗患者组的死亡和复发风险,但对接受PC治疗的患者组(仅DNA损伤剂)没有影响。发现短CRNDE剪接变体(FJ466686)的过表达具有更高的相关性:风险比(HR)6.072,95%置信区间(CI)1.814 - 20.32,p = 0.003(死亡风险);HR 15.53,95% CI 3.812 - 63.28,p < 0.001(复发风险)。此外,TP53蛋白的积累与肿瘤细胞中两种CRNDE转录本的表达降低相关。我们的结果表明CRNDE是卵巢癌女性患者预后不良的潜在标志物,并表明其意义取决于所使用的治疗方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f808/4791275/291853cfa136/oncotarget-06-43897-g001.jpg

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