外周血循环肿瘤细胞对早期胃癌的诊断和预后评估价值
|
摘要
目的探讨外周血循环肿瘤细胞(CTC)对早期胃癌(EGC)的诊断和预后评估价值。方法经胃镜检查发现胃黏膜病变、疑似EGC的189例患者根据病理诊断分为64例EGC患者和125例非EGC患者。采用Cell Search系统检测所有患者的CTC表达情况,以病理诊断结果为金标准,评价CTC的诊断效能。比较不同临床特征EGC患者的CTC表达情况,分析影响EGC患者预后的因素。结果 189例患者中,24例患者的CTC呈阳性,均为EGC患者,CTC诊断EGC的灵敏度为37.50%,特异度为100%,阳性预测值为100%,阴性预测值为75.76%,准确率为78.84%。CTC阳性与CTC阴性EGC患者的淋巴结转移情况、脉管癌栓情况比较,差异均有统计学意义(P﹤0.01)。CTC阳性、有淋巴结转移、有脉管癌栓的EGC患者的复发或转移率均高于CTC阴性、无淋巴结转移、无脉管癌栓的患者,差异均有统计学意义(P﹤0.05);不同性别、年龄、肿瘤位置、浸润深度、分化程度和大体病理类型的EGC患者的复发或转移情况比较,差异均无统计学意义(P﹥0.05)。结论应用Cell Search系统检测CTC对EGC的诊断效能较低,但可作为淋巴结转移和预后不良的参考指标。
Objective To study the diagnostic and prognostic value of peripheral circulating tumor cells(CTC) in early gastric cancer(EGC). Method A total of 189 patients with gastric mucosal lesion and suspected EGC under gastroscopy were included in the study. After pathological examination, 64 were diagnosed as EGC and 125 were diagnosed as nongastric cancer. Cell Search system was used to detect the CTC in all patients. The diagnostic efficiency of CTC was evaluated with pathological diagnosis as the gold standard. CTC expression in EGC patients with different clinical characteristics were compared, and the factors affecting the prognosis of patients with EGC were analyzed. Result Twenty-four out of 189 patients were with positive CTC, all of them were EGC patients. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate of CTC for diagnosing EGC were 37.50%, 100%, 100%, 75.76% and78.84%, respectively. There were significant differences in lymph node metastasis and vascular carcinoma thrombus between patients with positive and negative CTC(P<0.01). The recurrence or metastasis rate of patients with positive CTC,presence of lymph node metastasis and vascular carcinoma thrombus was significantly higher than those with negative CTC, absence of lymph node metastasis and vascular carcinoma thrombus(P<0.05); nonetheless, there were no statistically significant differences on recurrence or metastasis rate among different gender, age, tumor location, depth of invasion,degree of differentiation and general pathological types in EGC patients(P>0.05). Conclusion CTC detected by Cell Search system is inefficient in the diagnosis of EGC, but it can be used as a reference index for lymph node metastasis and poor prognosis.
Objective To study the diagnostic and prognostic value of peripheral circulating tumor cells(CTC) in early gastric cancer(EGC). Method A total of 189 patients with gastric mucosal lesion and suspected EGC under gastroscopy were included in the study. After pathological examination, 64 were diagnosed as EGC and 125 were diagnosed as nongastric cancer. Cell Search system was used to detect the CTC in all patients. The diagnostic efficiency of CTC was evaluated with pathological diagnosis as the gold standard. CTC expression in EGC patients with different clinical characteristics were compared, and the factors affecting the prognosis of patients with EGC were analyzed. Result Twenty-four out of 189 patients were with positive CTC, all of them were EGC patients. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate of CTC for diagnosing EGC were 37.50%, 100%, 100%, 75.76% and78.84%, respectively. There were significant differences in lymph node metastasis and vascular carcinoma thrombus between patients with positive and negative CTC(P<0.01). The recurrence or metastasis rate of patients with positive CTC,presence of lymph node metastasis and vascular carcinoma thrombus was significantly higher than those with negative CTC, absence of lymph node metastasis and vascular carcinoma thrombus(P<0.05); nonetheless, there were no statistically significant differences on recurrence or metastasis rate among different gender, age, tumor location, depth of invasion,degree of differentiation and general pathological types in EGC patients(P>0.05). Conclusion CTC detected by Cell Search system is inefficient in the diagnosis of EGC, but it can be used as a reference index for lymph node metastasis and poor prognosis.
引文
[1]Pérez-Mendoza A,Zárate-GuzmánáM,Galvis García ES,et al.Systematic alphanumeric-coded endoscopy versus chromoendoscopy for the detection of precancerous gastric lesions and early gastric cancer in subjects at average risk for gastric cancer[J].Rev Gastroenterol Mex,2018,83(2):117-124.
[2]邱洪波,王旋,何甜,等.ESD与传统手术治疗早期胃癌的疗效及对术后免疫应激反应和远期生存率的影响[J].癌症进展,2018,16(12):1529-1531;1561.
[3]Paoletti C,Hayes DF.Circulating tumor cells[J].Adv Exp Med Biol,2016,882:235-258.
[4]Kang HM,Kim GH,Jeon HK,et al.Circulating tumor cells detected by lab-on-a-disc:role in early diagnosis of gastric cancer[J].PLoS One,2017,12(6):e0180251.
[5]Hasuike N,Ono H,Boku N,et al.A non-randomized confirmatory trial of an expanded indication for endoscopic submucosal dissection for intestinal-type gastric cancer(cT1a):the Japan Clinical Oncology Group study(JCOG0607)[J].Gastric Cancer,2018,21(1):114-123.
[6]黄子凌,宇小婷,易祥华.循环肿瘤细胞检测技术的研究进展[J].同济大学学报(医学版),2018,39(3):123-127.
[7]郭仁宏.2013 NCCN胃癌临床实践指南(2013.V2)要点介绍及解读[J/OL].中国医学前沿杂志(电子版),2013,5(12):71-78[2014-01-03].http://www.yixueqianyan.cn/CN/abstract/abstract475.shtml.
[8]Ashworth TR.A case of cancer in which cells similar to those in the tumors were seen in the blood after death[J].Aust Med J,1869,14:146-147.
[9]Vaiopoulos AG,Kostakis ID,Gkioka E,et al.Detection of circulating tumor cells in colorectal and gastric cancer using a multiplex PCR assay[J].Anticancer Res,2014,34(6):3083-3092.
[10]Joosse SA,Gorges TM,Pantel K.Biology,detection and clinical implications of circulating tumor cells[J].Embo Molecular Medicine,2015,7(1):1-11.
[11]Omura H,Yoshida N,Hayashi T,et al.Interobserver agreement in detection of"white globe appearance"and the ability of educational lectures to improve the diagnosis of gastric lesions[J].Gastric Cancer,2017,20(4):620-628.
[12]Tang L,Zhao S,Liu W,et al.Diagnostic accuracy of circulating tumor cells detection in gastric cancer:systematic review and meta-analysis[J].BMC Cancer,2013,13:314.
[13]Koga T,Tokunaga E,Sumiyoshi Y,et al.Detection of circulating gastric cancer cells in peripheral blood using realtime quantitative RT-PCR[J].Hepatogastroenterology,2008,55(84):1131-1135.
[14]Ikeguchi M,Ohro S,Maeda Y,et al.Detection of cancer cells in the peripheral blood of gastric cancer patients[J].Int J Mol Med,2003,11(2):217-221.
[15]王振丹.ISET联合细胞免疫荧光检测循环肿瘤细胞技术体系的建立及其临床研究[D].济南:济南大学,2015.
[16]Kim B,Kim YS,Ahn HM,et al.Peroxiredoxin 5 overexpression enhances tumorigenicity and correlates with poor prognosis in gastric cancer[J].Int J Oncol,2017,51(1):298-306.
[17]Shimazu K,Fukuda K,Yoshida T,et al.High circulating tumor cell concentrations in a specific subtype of gastriccancer with diffuse bone metastasis at diagnosis[J].World J Gastroenterol,2016,22(26):6083-6088.
[18]黄名威,吴留成,周帆,等.循环肿瘤细胞参与肿瘤复发转移机制的研究进展[J].中国癌症防治杂志,2018,10(1):51-55.
[19]黄宝俊,孙哲,王振宁,等.早期胃癌术后复发、转移临床病理因素分析(附629例报告)[J].中国实用外科杂志,2015,35(10):1091-1094.
[20]Msaouel P,Koutsilieris M.Diagnostic value of circulating tumor cell detection in bladder and urothelial cancer:systematic review and meta-analysis[J].BMC Cancer,2011,11:336.
[21]Ochiai T,Ominami M,Nagami Y,et al.Lymph node metastasis of mixed adenoneuroendocrine carcinoma after curative resection using the expanded criteria for early gastric cancer[J].Intern Med,2018,57(19):2837-2842.
[22]Brungs D,Lynch D,Luk AW,et al.Cryopreservation for delayed circulating tumor cell isolation is a valid strategy for prognostic association of circulating tumor cells in gastroesophageal cancer[J].World J Gastroenterol,2018,24(7):810-818.(收稿日期:2018-12-29)
[2]邱洪波,王旋,何甜,等.ESD与传统手术治疗早期胃癌的疗效及对术后免疫应激反应和远期生存率的影响[J].癌症进展,2018,16(12):1529-1531;1561.
[3]Paoletti C,Hayes DF.Circulating tumor cells[J].Adv Exp Med Biol,2016,882:235-258.
[4]Kang HM,Kim GH,Jeon HK,et al.Circulating tumor cells detected by lab-on-a-disc:role in early diagnosis of gastric cancer[J].PLoS One,2017,12(6):e0180251.
[5]Hasuike N,Ono H,Boku N,et al.A non-randomized confirmatory trial of an expanded indication for endoscopic submucosal dissection for intestinal-type gastric cancer(cT1a):the Japan Clinical Oncology Group study(JCOG0607)[J].Gastric Cancer,2018,21(1):114-123.
[6]黄子凌,宇小婷,易祥华.循环肿瘤细胞检测技术的研究进展[J].同济大学学报(医学版),2018,39(3):123-127.
[7]郭仁宏.2013 NCCN胃癌临床实践指南(2013.V2)要点介绍及解读[J/OL].中国医学前沿杂志(电子版),2013,5(12):71-78[2014-01-03].http://www.yixueqianyan.cn/CN/abstract/abstract475.shtml.
[8]Ashworth TR.A case of cancer in which cells similar to those in the tumors were seen in the blood after death[J].Aust Med J,1869,14:146-147.
[9]Vaiopoulos AG,Kostakis ID,Gkioka E,et al.Detection of circulating tumor cells in colorectal and gastric cancer using a multiplex PCR assay[J].Anticancer Res,2014,34(6):3083-3092.
[10]Joosse SA,Gorges TM,Pantel K.Biology,detection and clinical implications of circulating tumor cells[J].Embo Molecular Medicine,2015,7(1):1-11.
[11]Omura H,Yoshida N,Hayashi T,et al.Interobserver agreement in detection of"white globe appearance"and the ability of educational lectures to improve the diagnosis of gastric lesions[J].Gastric Cancer,2017,20(4):620-628.
[12]Tang L,Zhao S,Liu W,et al.Diagnostic accuracy of circulating tumor cells detection in gastric cancer:systematic review and meta-analysis[J].BMC Cancer,2013,13:314.
[13]Koga T,Tokunaga E,Sumiyoshi Y,et al.Detection of circulating gastric cancer cells in peripheral blood using realtime quantitative RT-PCR[J].Hepatogastroenterology,2008,55(84):1131-1135.
[14]Ikeguchi M,Ohro S,Maeda Y,et al.Detection of cancer cells in the peripheral blood of gastric cancer patients[J].Int J Mol Med,2003,11(2):217-221.
[15]王振丹.ISET联合细胞免疫荧光检测循环肿瘤细胞技术体系的建立及其临床研究[D].济南:济南大学,2015.
[16]Kim B,Kim YS,Ahn HM,et al.Peroxiredoxin 5 overexpression enhances tumorigenicity and correlates with poor prognosis in gastric cancer[J].Int J Oncol,2017,51(1):298-306.
[17]Shimazu K,Fukuda K,Yoshida T,et al.High circulating tumor cell concentrations in a specific subtype of gastriccancer with diffuse bone metastasis at diagnosis[J].World J Gastroenterol,2016,22(26):6083-6088.
[18]黄名威,吴留成,周帆,等.循环肿瘤细胞参与肿瘤复发转移机制的研究进展[J].中国癌症防治杂志,2018,10(1):51-55.
[19]黄宝俊,孙哲,王振宁,等.早期胃癌术后复发、转移临床病理因素分析(附629例报告)[J].中国实用外科杂志,2015,35(10):1091-1094.
[20]Msaouel P,Koutsilieris M.Diagnostic value of circulating tumor cell detection in bladder and urothelial cancer:systematic review and meta-analysis[J].BMC Cancer,2011,11:336.
[21]Ochiai T,Ominami M,Nagami Y,et al.Lymph node metastasis of mixed adenoneuroendocrine carcinoma after curative resection using the expanded criteria for early gastric cancer[J].Intern Med,2018,57(19):2837-2842.
[22]Brungs D,Lynch D,Luk AW,et al.Cryopreservation for delayed circulating tumor cell isolation is a valid strategy for prognostic association of circulating tumor cells in gastroesophageal cancer[J].World J Gastroenterol,2018,24(7):810-818.(收稿日期:2018-12-29)