【文摘发布】MicroRNA表达谱模式有助于鉴别胰腺癌，正常胰腺和慢性胰腺炎

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Title: MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis.

Author:Bloomston M, Frankel WL, Petrocca F, olinia S, Alder H, Hagan JP, Liu CG, Bhatt D, Taccioli C, Croce CM.

Resource: JAMA. 2007 May 2;297(17):1901-8．

Abstract: CONTEXT: While global microRNA (miRNA) expression patterns of many embryologic, physiologic, and oncogenic processes hae been described, description of the role of miRNAs in ductal adenocarcinoma of the pancreas is lacking. OBJECTIE: To define the expression pattern of miRNAs in pancreatic cancer and compare it with those of normal pancreas and chronic pancreatitis. DESIGN AND SETTING: Specimens were obtained at a National Cancer Institute-designated comprehensie cancer center from patients with ductal adenocarcinoma of the pancreas (n = 65) or chronic pancreatitis (n = 42) (January 2000-December 2005). All patients underwent curatie pancreatectomy; those with pancreatic cancer were chemotherapy-naie. RNA harested from resected pancreatic cancers and matched benign adjacent pancreatic tissue as well as from chronic pancreatitis specimens was hybridized to miRNA microarrays. MAIN OUTCOME MEASURES: Identification of differentially expressed miRNAs that could differentiate pancreatic cancer from normal pancreas, chronic pancreatitis, or both, as well as a pattern of miRNA expression predictie of long-term (>24 months) surial. Significance of Analysis of Microarrays and Prediction of Analysis of Microarrays were undertaken to identify miRNAs predictie of tissue type and prognosis. P alues were calculated by t test, adjusted for multiple testing. Kaplan-Meier surial cures were constructed using mean miRNA expression (high s low) as threshold and compared by log-rank analysis. RESULTS: Twenty-one miRNAs with increased expression and 4 with decreased expression were identified that correctly differentiated pancreatic cancer from benign pancreatic tissue in 90% of samples by cross alidation. Fifteen oerexpressed and 8 underexpressed miRNAs differentiated pancreatic cancer from chronic pancreatitis with 93% accuracy. A subgroup of 6 miRNAs was able to distinguish long-term suriors with node-positie disease from those dying within 24 months. Finally, high expression of miR-196a-2 was found to predict poor surial (median, 14.3 months [95% confidence interal, 12.4-16.2] s 26.5 months [95% confidence interal, 23.4-29.6]; P = .009). CONCLUSIONS: Pancreatic cancer may hae a distinct miRNA expression pattern that may differentiate it from normal pancreas and chronic pancreatitis. miRNA expression patterns may be able to distinguish between long- and short-term suriors, but these findings need to be alidated in other study populations.

PMID:17473300

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Title: MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis.
题目：微RAN表达模式可鉴别胰腺癌
Author:Bloomston M, Frankel WL, Petrocca F, olinia S, Alder H, Hagan JP, Liu CG, Bhatt D, Taccioli C, Croce CM.

Resource: JAMA. 2007 May 2;297(17):1901-8．
来源：美国医师协会杂志 2007年5月2日，297卷17期，页码：1901-1908
Abstract: CONTEXT: While global microRNA (miRNA) expression patterns of many embryologic, physiologic, and oncogenic processes hae been described, description of the role of miRNAs in ductal adenocarcinoma of the pancreas is lacking.
摘要：背景：虽然整体微RNA表达模式在许多胚胎学、生理学和致癌过程都有研究报道，但在胰腺导管癌微RNA的作用还不清楚。

OBJECTIE: To define the expression pattern of miRNAs in pancreatic cancer and compare it with those of normal pancreas and chronic pancreatitis.
目的：了解胰腺癌微RNA表达模式，并与正常胰腺和慢性胰腺炎比较。
DESIGN AND SETTING: Specimens were obtained at a National Cancer Institute-designated comprehensie cancer center from patients with ductal adenocarcinoma of the pancreas (n = 65) or chronic pancreatitis (n = 42) (January 2000-December 2005). All patients underwent curatie pancreatectomy; those with pancreatic cancer were chemotherapy-naie. RNA harested from resected pancreatic cancers and matched benign adjacent pancreatic tissue as well as from chronic pancreatitis specimens was hybridized to miRNA microarrays.
研究设计和环境：标本获取于国立癌症研究所命名的综合癌症中心收治的65例胰腺癌和42例慢性胰腺炎患者（2000年1月－2005年12月）。所有患者均行根治性胰腺切除术；胰腺癌患者未行术前化疗。从切除胰腺肿瘤和临近的胰腺正常组织及慢性胰腺炎标本配对，RNA提取、杂合、miRNA微列阵。
MAIN OUTCOME MEASURES: Identification of differentially expressed miRNAs that could differentiate pancreatic cancer from normal pancreas, chronic pancreatitis, or both, as well as a pattern of miRNA expression predictie of long-term (>24 months) surial. Significance of Analysis of Microarrays and Prediction of Analysis of Microarrays were undertaken to identify miRNAs predictie of tissue type and prognosis. P alues were calculated by t test, adjusted for multiple testing. Kaplan-Meier surial cures were constructed using mean miRNA expression (high s low) as threshold and compared by log-rank analysis.
主要结果测量：从不同微RNA表达模式鉴定出某一表达模式可预测患者长期生存率，并可从貌似正常胰腺、慢性胰腺炎标本鉴别胰腺癌。微列阵分析的重要意义在于可从众多微RNA中鉴别出可预测组织类型和预后的微RNA。多次测量校正后，t检验计算p值。平均微RNA表达水平（高表达s低表达）作为阈值形成卡普兰-迈耶存活曲线与时序分析形成的阶梯曲线加以比较。
RESULTS: Twenty-one miRNAs with increased expression and 4 with decreased expression were identified that correctly differentiated pancreatic cancer from benign pancreatic tissue in 90% of samples by cross alidation. Fifteen oerexpressed and 8 underexpressed miRNAs differentiated pancreatic cancer from chronic pancreatitis with 93% accuracy. A subgroup of 6 miRNAs was able to distinguish long-term suriors with node-positie disease from those dying within 24 months. Finally, high expression of miR-196a-2 was found to predict poor surial (median, 14.3 months [95% confidence interal, 12.4-16.2] s 26.5 months [95% confidence interal, 23.4-29.6]; P = .009).
结果：经交叉确认，鉴定出21个高表达微RNA序列和4个低表达模式可从90%良性胰腺标本准确鉴别出胰腺癌。15个高表达和8个低表达微RNA序列从慢性胰腺炎标本鉴别出胰腺癌准确率为93%。亚组6个微RNA序列可鉴别淋巴结阳性胰腺癌长期存活患者与2年内死亡患者。表达微RNA-196a-2 患者预后差。[中位存活时间14.3月（95％可信区间12.4-16.2）s 26.5月（95%可信区间23.4-29.6；p=0.009]。
CONCLUSIONS: Pancreatic cancer may hae a distinct miRNA expression pattern that may differentiate it from normal pancreas and chronic pancreatitis. miRNA expression patterns may be able to distinguish between long- and short-term suriors, but these findings need to be alidated in other study populations.
结论：胰腺癌可能存在一个异于正常胰腺和慢性胰腺炎的微RNA表达模式，微RNA表达模式可能用来判断预后，以上研究结果需在其他研究人群加以验证。
PMID:17473300
编译：中文字数（604）

美国俄亥俄州Soloe 研究所詹姆士肿瘤医院肿瘤外科Bloomston M博士的研究表明：胰腺癌可能存在一个异于正常胰腺和慢性胰腺炎的微RNA表达模式，微RNA表达模式可能用来判断预后，以上研究结果需在其他研究人群加以验证。（JAMA. 2007 May 2;297(17):1901-8）
虽然整体微RNA表达模式在许多胚胎学、生理学和致癌过程都有研究报道，但在胰腺导管癌微RNA的作用还不清楚。基于此，Bloomston M博士等人设计了本实验。标本获取于国立癌症研究所命名的综合癌症中心收治的65例胰腺癌和42例慢性胰腺炎患者（2000年1月－2005年12月）。所有患者均行根治性胰腺切除术；胰腺癌患者未行术前化疗。从切除胰腺肿瘤和临近的胰腺正常组织及慢性胰腺炎标本配对，RNA提取、杂合、miRNA微列阵。主要结果测量：从不同微RNA表达模式鉴定出某一表达模式可预测患者长期生存率，并可从貌似正常胰腺、慢性胰腺炎标本鉴别胰腺癌。微列阵分析的重要意义在于可从众多微RNA中鉴别出可预测组织类型和预后的微RNA。多次测量校正后，t检验计算p值。平均微RNA表达水平（高表达s低表达）作为阈值形成卡普兰-迈耶存活曲线与时序分析形成的阶梯曲线加以比较。
结果显示：经交叉确认，鉴定出21个高表达微RNA序列和4个低表达模式可从90%良性胰腺标本准确鉴别出胰腺癌。15个高表达和8个低表达微RNA序列从慢性胰腺炎标本鉴别出胰腺癌准确率为93%。亚组6个微RNA序列可鉴别淋巴结阳性胰腺癌长期存活患者与2年内死亡患者。表达微RNA-196a-2 患者预后差。[中位存活时间14.3月（95％可信区间12.4-16.2）s 26.5月（95%可信区间23.4-29.6；p=0.009]。