胃癌、结直肠癌及对照组中肿瘤类型M2丙酮酸激酶的表达
Tumor type M2 pyruvate kinase expression in gastric cancer, colorectal cancer and controls.
作者信息
Zhang Bo, Chen Jian-Ying, Chen Dao-Da, Wang Guo-Bin, Shen Ping
机构信息
Department of General Surgery, Affiliated Xiehe Hospital of Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
出版信息
World J Gastroenterol. 2004 Jun 1;10(11):1643-6. doi: 10.3748/wjg.v10.i11.1643.
AIM
Tumor formation is generally linked to an expansion of glycolytic phosphometabolite pools and aerobic glycolytic flux rates. To achieve this, tumor cells generally overexpress a special glycolytic isoenzyme, termed pyruvate kinase type M(2). The present study was designed to evaluate the use of a new tumor marker, tumor M(2)-PK, in discriminating gastrointestinal cancer patients from healthy controls, and to compare with the reference tumor markers CEA and CA72-4.
METHODS
The concentration of tumor M(2)-PK in body fluids could be quantitatively determined by a commercially available enzyme-linked immunosorbent assay (ELISA)-kit (ScheBo Tech, Giessen, Germany). By using this kit, the tumor M(2)-PK concentration was measured in EDTA-plasma of 108 patients. For the healthy blood donors a cut-off value of 15 U/mL was evaluated, which corresponded to 90% specificity. Overall 108 patients were included in this study, 54 patients had a histological confirmed gastric cancer, 54 patients colorectal cancer, and 20 healthy volunteers served as controls.
RESULTS
The cut-off value to discriminate patients from controls was established at 15 U/mL for tumor M(2)-PK. The mean tumor M(2)-PK concentration of gastric cancer was 26.937 U/mL. According to the TNM stage system, the mean tumor M(2)-PK concentration of stage I was 16.324 U/mL, of stage II 15.290 U/mL, of stage III 30.289 U/mL, of stage IV 127.31 U/mL, of non-metastasis 12.854 U/mL and of metastasis 35.711 U/mL. The mean Tumor M(2)-PK concentration of colorectal cancer was 30.588 U/mL. According to the Dukes stage system, the mean tumor M(2)-PK concentration of Dukes A was 16.638 U/mL, of Dukes B 22.070 U/mL, and of Dukes C 48.024 U/ml, of non-metastasis 19.501 U/mL, of metastasis 49.437 U/mL. The mean tumor M(2)-PK concentration allowed a significant discrimination of colorectal cancers (30.588 U/mL) from controls (10.965 U/mL) (P<0.01), and gastric cancer (26.937 U/mL) from controls (10.965 U/mL) (P<0.05). The overall sensitivity of tumor M(2)-PK for colorectal cancer was 68.52%, while that of CEA was 43.12%. In gastric cancer, tumor M(2)-PK showed a high sensitivity of 50.47%, while CA72-4 showed a sensitivity of 35.37%.
CONCLUSION
Tumor M(2)-PK has a higher sensitivity than markers CEA and CA72-4, and is a valuable tumor marker for the detection of gastrointestinal cancer.
目的
肿瘤形成通常与糖酵解磷酸代谢物池的扩大和有氧糖酵解通量率有关。为实现这一点，肿瘤细胞通常会过度表达一种特殊的糖酵解同工酶，即M(2)型丙酮酸激酶。本研究旨在评估一种新的肿瘤标志物——肿瘤M(2)-PK在区分胃肠道癌患者与健康对照者方面的应用，并与参考肿瘤标志物癌胚抗原（CEA）和糖类抗原72-4（CA72-4）进行比较。
方法
体液中肿瘤M(2)-PK的浓度可通过市售的酶联免疫吸附测定（ELISA）试剂盒（德国吉森市ScheBo Tech公司）进行定量测定。使用该试剂盒，对108例患者的乙二胺四乙酸（EDTA）血浆中的肿瘤M(2)-PK浓度进行了测量。对于健康献血者，评估出的临界值为15 U/mL，其对应90%的特异性。本研究共纳入108例患者，其中54例经组织学确诊为胃癌，54例为结直肠癌，20名健康志愿者作为对照。
结果
肿瘤M(2)-PK区分患者与对照的临界值确定为15 U/mL。胃癌患者肿瘤M(2)-PK的平均浓度为26.937 U/mL。根据TNM分期系统，I期患者肿瘤M(2)-PK的平均浓度为16.324 U/mL，II期为15.290 U/mL，III期为30.289 U/mL，IV期为127.31 U/mL，无转移患者为12.854 U/mL，有转移患者为35.711 U/mL。结直肠癌患者肿瘤M(2)-PK的平均浓度为30.588 U/mL。根据Dukes分期系统，Dukes A期患者肿瘤M(2)-PK的平均浓度为16.638 U/mL，Dukes B期为22.070 U/mL，Dukes C期为48.024 U/mL，无转移患者为19.501 U/mL，有转移患者为49.437 U/mL。肿瘤M(2)-PK的平均浓度能够显著区分结直肠癌患者（30.588 U/mL）与对照者（10.965 U/mL）（P<0.01），以及胃癌患者（26.937 U/mL）与对照者（10.965 U/mL）（P<0.05）。肿瘤M(2)-PK对结直肠癌的总体敏感性为68.52%，而CEA为43.12%。在胃癌中，肿瘤M(2)-PK表现出50.47%的高敏感性，而CA72-4的敏感性为35.37%。
结论
肿瘤M(2)-PK比标志物CEA和CA72-4具有更高的敏感性，是检测胃肠道癌的一种有价值的肿瘤标志物。
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