Identification of specific pancreatic serum protein marker for early diagnosis by using ProteinChip technology

利用 ProteinChip 技术鉴定特异性胰腺血清蛋白标记物以进行早期诊断

• 批准号: 18591501
• 负责人: NOZAWA Satoshi
• 金额: $ 2.53万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591501/
• 关键词: proteome; cancer; protein; knockdown; pancreatic cancer; 発現制御

We compared pre- and postoperative serum protein profiling obtained from pancreatic cancer patients who had curative pancreatectomy using surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS). The peak intensity levels of both 6630 and 6420 Da were significantly higher in the preoperative serum than in the postoperative serum (p<0. 002). Sequential amino acid analysis identified these proteins to be apolipoprotein C-1 (ApoC-1). Furthermore, ApoC-1 was abundantly expressed in pancreas neoplastic epithelium, and was detected in the culture medium of the pancreatic cancer cell line in vitro, which suggests that cancer cells secrete ApoC-1. The high level of ApoC-1 in preoperative serum significantly correlated with poor prognosis in the preoperative serum samples from an independent group of 69 pancreatic cancer patients who had surgical resection of cancer. We also performed the receiver-operator-characteristics (ROC) analysis between patients with survival time more and less than two years. The respective area under the ROC curve (AUC) was 0. 66 for ApoC-1 peak intensity and 0. 60 for CA19-9 level. These results indicated that serum ApoC-1 peak intensity had the better ability as a prognostic marker than serum CA19-9 level.Inhibition of ApoC-1 expression by siRNA suppressed cell proliferation and induced apoptosis of pancreatic cancer cells. The specific expression of ApoC-1 and its rote in preventing from spontaneous apoptosis in pancreatic cancer cells suggest that ApoC-1 contributes to the aggressiveness of pancreatic cancer and will be useful as a new therapeutic target.

我们比较了使用表面增强激光解吸电离飞行时间质谱（SELDI-TOF MS）进行根治性胰腺切除术的胰腺癌患者的术前和术后血清蛋白质谱。术前血清中6630和6420 Da的峰值强度水平均明显高于术后血清（p<0. 05）。002）。氨基酸序列分析表明这些蛋白质是载脂蛋白C-1（ApoC-1）。此外，ApoC-1在胰腺肿瘤上皮中大量表达，并且在体外胰腺癌细胞系的培养基中检测到，这表明癌细胞分泌ApoC-1。术前血清中ApoC-1的高水平与来自69名手术切除癌症的胰腺癌患者的独立组的术前血清样本中的不良预后显著相关。我们还对生存时间大于和小于两年的患者进行了受试者操作者特征（ROC）分析。相应的ROC曲线下面积（AUC）为0。ApoC-1峰强度为66，CA 19 -9水平60。提示血清ApoC-1峰值强度比血清CA 19 -9水平更能作为胰腺癌的预后指标，siRNA抑制ApoC-1表达可抑制胰腺癌细胞增殖并诱导其凋亡。ApoC-1在胰腺癌细胞中的特异性表达及其在防止自发性凋亡中的作用提示ApoC-1参与胰腺癌的侵袭性，有望成为胰腺癌治疗的新靶点。

项目成果

Combined vascular resection in operative resection for hilar cholangiocarcinoma: Does it work or not?

• DOI: 10.1016/j.surg.2006.09.016
• 发表时间: 2007-05-01
• 期刊: SURGERY
• 影响因子: 3.8
• 作者: Miyazaki, Masaru;Kato, Atsushi;Nozawa, Satoshi
• 通讯作者: Nozawa, Satoshi

Increased plasma levels of IL-6 and IL-8 are associated with surgical site infection after pancreaticoduodenectomy

• DOI: 10.1097/01.mpa.0000202959.63977.5c
• 发表时间: 2006-03-01
• 期刊: PANCREAS
• 影响因子: 2.9
• 作者: Kimura, Fumio;Shimizu, Hiroaki;Miyazaki, Masaru
• 通讯作者: Miyazaki, Masaru

Apolipoprotein C-1 maintains cell survival by preventing from apoptosis in pancreatic cancer cells

• DOI: 10.1038/sj.onc.1210951
• 发表时间: 2008-05-01
• 期刊: ONCOGENE
• 影响因子: 8
• 作者: Takano, S.;Yoshitomi, H.;Miyazaki, M.
• 通讯作者: Miyazaki, M.

Longitudinal Pancreatojejunostomy with Distal Pancreatectomy for a Pancreatic Tail Cancer on Chronic Pancreatitis

慢性胰腺炎胰尾癌纵向胰空肠吻合术联合远端胰腺切除术

• 发表时间: 2006
• 作者: Uchinami;H.;Uchinami H;Matsumura Y;打波 宇;樋田泰浩;阿部ゆき;石川慶大;Abe Y;吉岡達也;Hida Y;Ishikawa K;Yoshioka T;樋田泰浩;Hida Y;樋田泰浩;石川慶大;Hida Y;Ishikawa K;樋田泰浩;石川慶大;Hida Y;Ishikawa K;樋田泰浩;Hida Y;長谷龍之介;角谷昌俊;Kadoya T;Hase R;Masaru Miyazaki;Masaru Miyazaki;Masaru Miyazaki;Fumio Kimura;Fumio Kimura;Shigetsugu Takano;Shigetsugu Takano;Shigetsugu Takano;Satoshi Nozawa;Satoshi Nozawa;Satoshi Nozawa;Shigetsugu Takano;Shigetsugu Takano;Satoshi Nozawa
• 通讯作者: Satoshi Nozawa

Identification of Apolipoprotein C-1 as a novel prognostic serum markerof pancreatic cancer and its expression in cancer cells.

载脂蛋白 C-1 作为胰腺癌新型预后血清标志物的鉴定及其在癌细胞中的表达。

• 发表时间: 2006
• 作者: Uchinami;H.;Uchinami H;Matsumura Y;打波 宇;樋田泰浩;阿部ゆき;石川慶大;Abe Y;吉岡達也;Hida Y;Ishikawa K;Yoshioka T;樋田泰浩;Hida Y;樋田泰浩;石川慶大;Hida Y;Ishikawa K;樋田泰浩;石川慶大;Hida Y;Ishikawa K;樋田泰浩;Hida Y;長谷龍之介;角谷昌俊;Kadoya T;Hase R;Masaru Miyazaki;Masaru Miyazaki;Masaru Miyazaki;Fumio Kimura;Fumio Kimura;Shigetsugu Takano;Shigetsugu Takano;Shigetsugu Takano;Satoshi Nozawa;Satoshi Nozawa;Satoshi Nozawa;Shigetsugu Takano
• 通讯作者: Shigetsugu Takano