Gene expression profiling of paraffin-embedded primary melanoma using the DASL assay identifies increased osteopontin expression as predictive of reduced relapse-free survival.
Gene expression profiling of paraffin-embedded primary melanoma using the DASL assay identifies increased osteopontin expression as predictive of reduced relapse-free survival.
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DOI：
10.1158/1078-0432.ccr-09-1631
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发表时间：
2009-11-15
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影响因子：
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通讯作者：
Newton-Bishop J
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文献类型：
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作者：
Conway C;Mitra A;Jewell R;Randerson-Moor J;Lobo S;Nsengimana J;Edward S;Sanders DS;Cook M;Powell B;Boon A;Elliott F;de Kort F;Knowles MA;Bishop DT;Newton-Bishop J
黑色素瘤的基因表达研究很少，因为肿瘤很小，冷冻保存很少可能。本研究的目的是评估Illumina DASL Array Human Cancer Panel在福尔马林固定的黑色素瘤原发性肿瘤中的基因表达研究，并鉴定预后生物标志物。使用组织微阵列针对来自两项研究的原发性肿瘤进行取样。研究1：2000-2006年招募的254例黑色素瘤患者。研究2：218例肿瘤，来自接受前哨淋巴结活检患者的病例对照研究。从76%的块中获得RNA。1.4%的样本分析失败（DASL芯片上检测到的502个基因中不到250个基因的转录本）。肿瘤块的年龄增加和肿瘤中黑色素的增加与检测到的基因数量减少有关。在研究1中，与无复发生存率相关的表达差异最大的基因是骨桥蛋白（SPP 1，p=2.11×10−6），在研究2中获得了支持性证据，用作验证集（p=0.006）（未校正数据）。研究1中的骨桥蛋白水平仍然是无复发生存期的重要预测因子，当数据根据年龄、性别、肿瘤部位和复发的组织学预测因子进行校正时。与骨桥蛋白表达相关性最强的基因是PBX 1、BIRC 5（Survivin）和HLF。从74%的原发性黑色素瘤中获得了表达数据，并提供了骨桥蛋白表达是预后生物标志物的确证性证据。这些结果表明，预测性生物标志物研究可能使用来自成熟临床试验的存储块。
Gene expression studies in melanoma have been few because tumors are small and cryopreservation is rarely possible. The purpose of this study was to evaluate the Illumina DASL Array Human Cancer Panel for gene expression studies in formalin-fixed melanoma primary tumors, and to identify prognostic biomarkers. Primary tumors from two studies were sampled using a tissue microarray needle. Study 1: 254 tumors from a melanoma cohort recruited 2000-2006. Study 2: 218 tumors from a case-control study of patients undergoing sentinel node biopsy. RNA was obtained from 76% of blocks. 1.4% of samples failed analysis (transcripts from less than 250 of the 502 genes on the DASL chip detected). Increasing age of the block and increased melanin in the tumor were associated with reduced number of genes detected. The gene whose expression was most differentially expressed in association with relapse free survival in study 1 was osteopontin (SPP1, p=2.11×10−6) and supportive evidence for this was obtained in study 2 used as a validation set (p=0.006) (unadjusted data). Osteopontin level in study 1 remained a significant predictor of relapse free survival when data were adjusted for age, sex, tumor site and histological predictors of relapse. Genes whose expression correlated most strongly with osteopontin were PBX1, BIRC5 (Survivin) and HLF. Expression data were obtained from 74% of primary melanomas and provided confirmatory evidence that osteopontin expression is a prognostic biomarker. These results suggest that predictive biomarker studies may be possible using stored blocks from mature clinical trials.