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8号染色体长臂增加与透明细胞和乳头状肾细胞癌患者生存率之间的相关性。

The correlation between gain of chromosome 8q and survival in patients with clear and papillary renal cell carcinoma.

作者信息

Mehrazin Reza, Dulaimi Essel, Uzzo Robert G, Devarjan Karthik, Pei Jianming, Smaldone Marc C, Kutikov Alexander, Testa Joseph R, Al-Saleem Tahseen

机构信息

Department of Urology and Oncological Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Divisions of Pathology and Cancer Biology, Fox Chase Cancer Center-Temple Health System, Philadelphia, PA, USA.

出版信息

Ther Adv Urol. 2017 Oct 31;10(1):3-10. doi: 10.1177/1756287217732660. eCollection 2018 Jan.

Abstract

BACKGROUND

The proto-oncogene , located on chromosome 8q, can be upregulated through gain of 8q, causing alteration in biology of renal cell carcinoma (RCC). The aim of this study was to evaluate the prevalence of through chromosome 8q gain and to correlate findings with cancer-specific mortality (CSM), and overall survival (OS).

METHODS

Cytogenetic analysis by conventional or Chromosomal Genomic Microarray Analysis (CMA) was performed on 414 renal tumors. Nonclear and nonpapillary RCC were excluded. Impact of gain in chromosome 8q status on CSM, OS, and its correlation with clinicopathological variables were evaluated. CSM and OS were assessed using log-rank test and the Cox proportional hazards model.

RESULTS

A total of 297 RCC tumors with cytogenetic analysis were included. Gain of 8q was detected in 18 (6.1%) tumors (9 clear cell and 9 papillary RCC), using conventional method ( 11) or CMA ( 7). Gain of 8q was associated with higher T stage ( < 0.001), grade ( < 0.001), nodal involvement ( = 0.005), and distant metastasis ( < 0.001). No association between gain of 8q and age ( = 0.23), sex ( = 0.46), and Charlson comorbidity index (CCI, = 0.59) were seen. Gain of 8q was associated with an 8.38-fold [95% confidence interval (CI), 3.83-18.34, < 0.001] and 3.31-fold (95% CI, 1.56-7.04, = 0.001) increase in CSM and decrease in OS, respectively, at a median follow up of 56 months.

CONCLUSION

Chromosome 8q harbors the proto-oncogene , which can be upregulated by gain of 8q. Our findings suggest that gain of 8q, can predict aggressive tumor phenotype and inferior survival in RCC.

摘要

背景

位于8号染色体长臂的原癌基因可通过8号染色体长臂获得性改变而上调,从而导致肾细胞癌(RCC)生物学行为改变。本研究旨在评估8号染色体长臂获得性改变的发生率,并将研究结果与癌症特异性死亡率(CSM)和总生存期(OS)相关联。

方法

对414例肾肿瘤进行常规细胞遗传学分析或染色体基因组微阵列分析(CMA)。排除非透明和非乳头状肾细胞癌。评估8号染色体长臂状态获得性改变对CSM、OS的影响及其与临床病理变量的相关性。使用对数秩检验和Cox比例风险模型评估CSM和OS。

结果

共纳入297例进行了细胞遗传学分析的肾细胞癌肿瘤。使用传统方法(11例)或CMA(7例)在18例(6.1%)肿瘤(9例透明细胞肾细胞癌和9例乳头状肾细胞癌)中检测到8号染色体长臂获得性改变。8号染色体长臂获得性改变与更高的T分期(P<0.001)、分级(P<0.001)、淋巴结受累(P = 0.005)和远处转移(P<0.001)相关。未观察到8号染色体长臂获得性改变与年龄(P = 0.23)、性别(P = 0.46)和Charlson合并症指数(CCI,P = 0.59)之间存在关联。在中位随访56个月时,8号染色体长臂获得性改变分别与CSM增加8.38倍[95%置信区间(CI),3.83 - 18.34,P<0.001]和OS降低3.31倍(95%CI,1.56 - 7.04,P = 0.001)相关。

结论

8号染色体长臂含有原癌基因,其可通过8号染色体长臂获得性改变而上调。我们的研究结果表明,8号染色体长臂获得性改变可预测肾细胞癌侵袭性肿瘤表型和较差的生存期。

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