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大Tenascin-C剪接变体作为结直肠癌潜在生物标志物的临床意义

Clinical significance of large tenascin-C spliced variant as a potential biomarker for colorectal cancer.

作者信息

Takeda Akihiko, Otani Yoshihide, Iseki Hiroyoshi, Takeuchi Hideki, Aikawa Kimiyasu, Tabuchi Satoru, Shinozuka Nozomi, Saeki Toshiaki, Okazaki Yasushi, Koyama Isamu

机构信息

Department of Surgery and Surgical Oncology, Saitama Medical University, 38 Morohongo, Moroyama, Iruma, 350-0495, Saitama, Japan.

出版信息

World J Surg. 2007 Feb;31(2):388-94. doi: 10.1007/s00268-006-0328-6.

Abstract

BACKGROUND

Tenascin-C is an extracellular matrix protein forming various types of spliced variants. Low molecule variants are transiently present, but large spliced variants are predominantly overexpressed in proliferative processes or tumorigenesis in some varieties of cancer. However, the detection of the plasma level of large tenascin-C spliced variant (L-Tn-CSV) in colorectal cancer (CRC) has not been clarified. This study was performed to validate elevated plasma L-Tn-CSV levels as a possible biomarker for CRC.

MATERIALS AND METHODS

Plasma samples were obtained before resection and from time to time postoperatively and stored at -80 degrees C until assay. Plasma L-Tn-CSV levels were evaluated in patients with primary (n = 162) and with recurrent (n = 20) CRC, including 48 healthy volunteers, measured by ELISA.

RESULTS

The average plasma L-Tn-CSV concentrations of patients with primary CRC were 5,260 +/- 3,243.3 pg/ml and of patients with recurrent CRC 4,106 +/- 2,261.1 pg/ml, which were significantly elevated in comparison with those of healthy volunteers (2,364.3 +/- 7,49.6). The sensitivity for detecting CRC using plasma L-Tn-CSV was 56.6%, based on the mean +/- 2 SD of the concentrations of healthy controls (3,863.5), which was significantly higher than CEA (40.1%) and CA19-9 (23.6%). No obvious associations were evident between plasma L-Tn-CSV status and values of CEA and CA19-9 respectively. Statistically significant differences in plasma L-Tn-CSV were observed depending on tumor depth, lymph node metastasis, and TNM stage. Negative conversions of plasma L-Tn-CSV levels 6 months after resection were significantly higher in the completely curative resection group than in the non-curative groups (P < 0.001).

CONCLUSION

The plasma L-Tn-CSV may serve very well as a useful biomarker for tumor staging and postoperative monitoring of preoperatively positive CRC that is independent and exceeds conventional tumor markers.

摘要

背景

腱生蛋白-C是一种细胞外基质蛋白,可形成多种类型的剪接变体。低分子变体短暂存在,但在某些癌症的增殖过程或肿瘤发生中,大的剪接变体主要过度表达。然而,结直肠癌(CRC)中血浆大腱生蛋白-C剪接变体(L-Tn-CSV)水平的检测尚不清楚。本研究旨在验证血浆L-Tn-CSV水平升高作为CRC可能的生物标志物。

材料与方法

在切除术前及术后定期采集血浆样本,储存在-80℃直至检测。通过酶联免疫吸附测定法(ELISA)评估原发性CRC患者(n = 162)和复发性CRC患者(n = 20)的血浆L-Tn-CSV水平,其中包括48名健康志愿者。

结果

原发性CRC患者的血浆L-Tn-CSV平均浓度为5,260±3,243.3 pg/ml,复发性CRC患者为4,106±2,261.1 pg/ml,与健康志愿者(2,364.3±749.6)相比显著升高。基于健康对照浓度的平均值±2标准差(3,863.5),使用血浆L-Tn-CSV检测CRC的敏感性为56.6%,显著高于癌胚抗原(CEA,40.1%)和糖类抗原19-9(CA19-9,23.6%)。血浆L-Tn-CSV状态与CEA和CA19-9的值之间分别无明显关联。根据肿瘤深度、淋巴结转移和TNM分期,血浆L-Tn-CSV存在统计学显著差异。完全治愈性切除组术后6个月血浆L-Tn-CSV水平的阴性转化率显著高于非治愈性切除组(P < 0.001)。

结论

血浆L-Tn-CSV可能是一种非常有用的生物标志物,用于术前阳性CRC的肿瘤分期和术后监测,具有独立性且优于传统肿瘤标志物。

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