膀胱癌患者外周血中循环肿瘤细胞的监测及临床意义研究
|
摘要
目的研究膀胱癌患者外周血中循环肿瘤细胞(CTC)数目,探讨其对膀胱癌复发和转移的早期监测、临床疗效评价及预后判断的意义。方法选取87例膀胱癌患者及40例同期膀胱良性病变患者作为研究对象,根据肿瘤浸润深度将87例膀胱癌患者进一步分为非肌层浸润组(55例)和肌层浸润组(32例),膀胱良性病变患者作为对照组(40例)。采用上皮细胞黏附分子(EpCAM)芯片分选法检测外周血中CTC,比较各组治疗前及治疗过程中的CTC数量,比较不同CTC数量患者治疗后1年复发率。结果治疗前,对照组患者外周血中未检出CTC,非肌层浸润组患者CTC检出数为(9.38±11.35)/10 ml,明显少于肌层浸润组患者的(23.28±11.74)/10 ml,差异有统计学意义(P﹤0.01)。治疗过程中两组膀胱癌患者CTC检出数均逐渐减少,差异均有统计学意义(P﹤0.01)。未检出CTC的非肌层浸润组患者1年复发率低于检出CTC的非肌层浸润组患者,差异有统计学意义(P﹤0.05);CTC检出数为(0～20)/10 ml及≥21/10 ml的肌层浸润组患者的1年复发率比较,差异无统计学意义(P﹥0.05)。结论外周血中的CTC是膀胱癌预后不良的重要标志,对膀胱癌临床疗效评价、预后判断有重要价值。
Objective To investigate the expression of circulating tumor cell(CTC) in the peripheral blood of bladder cancer and to discuss its clinical significance in early diagnosis and evaluating the prognosis of bladder cancer. Method The research included 87 patients with bladder cancer who were further assigned into non-muscle-invasive bladder cancer group(n=55) and muscle-invasive bladder cancer group(n=32) according to the depth of invasion, besides, the 40 patients with benign bladder cancer during the same period were grouped as control(n=40). The CTC in peripheral blood of these subjects were detected by epithelial cell adhesion molecule(EpCAM)-based separation method, and the count of CTC in each group were compared before and during treatment, additionally, the 1-year recurrence rate of bladder cancer was also compared among patients with different CTC counts. Result Before treatment, the CTC were not detected in control group, while in non-muscle-invasion group the detected CTC count was(9.38±11.35)/10 ml, which was significantly less than that in muscle-invasion group at(23.28±11.74)/10 ml, and the difference was statistically significant(P<0.01). During treatment, the CTC counts in both groups decreased gradually, and the changes were statistically significant(P<0.01). The 1-year recurrence rate in non-muscle invasion group with undetectable CTC was significantly lower than that of muscle invasive bladder cancer patients with detectable CTC, indicating statistically significant difference(P<0.05); there was no evident difference regarding the 1-year recurrence rates among patients with CTC count of(0～20)/10 ml and ≥21/10 ml in muscle-invasion group(P>0.05). Conclusion Peripheral blood CTC is an important marker of poor prognosis of bladder cancer, and is reasonably crucial for evaluating the efficacy and predicting prognosis of bladder cancer.
Objective To investigate the expression of circulating tumor cell(CTC) in the peripheral blood of bladder cancer and to discuss its clinical significance in early diagnosis and evaluating the prognosis of bladder cancer. Method The research included 87 patients with bladder cancer who were further assigned into non-muscle-invasive bladder cancer group(n=55) and muscle-invasive bladder cancer group(n=32) according to the depth of invasion, besides, the 40 patients with benign bladder cancer during the same period were grouped as control(n=40). The CTC in peripheral blood of these subjects were detected by epithelial cell adhesion molecule(EpCAM)-based separation method, and the count of CTC in each group were compared before and during treatment, additionally, the 1-year recurrence rate of bladder cancer was also compared among patients with different CTC counts. Result Before treatment, the CTC were not detected in control group, while in non-muscle-invasion group the detected CTC count was(9.38±11.35)/10 ml, which was significantly less than that in muscle-invasion group at(23.28±11.74)/10 ml, and the difference was statistically significant(P<0.01). During treatment, the CTC counts in both groups decreased gradually, and the changes were statistically significant(P<0.01). The 1-year recurrence rate in non-muscle invasion group with undetectable CTC was significantly lower than that of muscle invasive bladder cancer patients with detectable CTC, indicating statistically significant difference(P<0.05); there was no evident difference regarding the 1-year recurrence rates among patients with CTC count of(0～20)/10 ml and ≥21/10 ml in muscle-invasion group(P>0.05). Conclusion Peripheral blood CTC is an important marker of poor prognosis of bladder cancer, and is reasonably crucial for evaluating the efficacy and predicting prognosis of bladder cancer.
引文
[1]易善红.我国膀胱癌诊治指南解读[J].中华临床医师杂志(电子版), 2013, 7(3):924-925.
[2]唐芮鹏. CTCs在膀胱癌转移及预后评估中的临床应用研究[D].昆明:昆明医科大学, 2017.
[3] Gorin MA, Verdone JE, van der Toom E, et al. Circulating tumour cells as biomarkers of prostate, bladder, and kidney cancer[J]. Nat Rev Urol, 2017, 14(2):90-97.
[4] Lima L, Neves M, Oliveira MI, et al. Sialyl-Tn identifies muscle-invasive bladder cancer basal and luminal subtypes facing decreased survival, being expressed by circulating tumor cells and metastases[J]. Urol Oncol, 2017, 35(12):675;e1; e8.
[5] Zhang Z, Fan W, Deng Q, et al. The prognostic and diagnostic value of circulating tumor cells in bladder cancer and upper tract urothelial carcinoma:a meta-analysis of 30 published studies[J]. Oncotarget, 2017, 8(35):59527-59538.
[6]那彦群,叶章群,孙光.中国泌尿外科疾病诊断治疗指南(2014版)[M].北京:人民卫生出版社, 2014:33-53.
[7] Zhang W, Xia W, Lv Z, et al. Liquid biopsy for cancer:circulating tumor cells, circulating free dna or exosomes?[J].Cell Physiol Biochem, 2017, 41(2):755-768.
[8]董建伟,夏凌,李攻科.循环肿瘤细胞富集技术研究进展[J].分析化学, 2018, 46(12):1851-1862.
[9] Politaki E, Agelaki S, Apostolaki S, et al. A comparison of three methods for the detection of circulating tumor cells in patients with early and metastatic breast cancer[J]. Cell Physiol Biochem, 2017, 44(2):594-606.
[10] Gabriel MT, Calleja LR, Chalopin A, et al. Circulating tumor cells:a review of non-EpCAM-based approaches for cell enrichment and isolation[J]. Clin Chem, 2016, 62(4):571-581.
[11] Chikaishi Y, Yoneda K, Ohnaga T, et al. EpCAM-independent capture of circulating tumor cells with a‘universal CTC-chip’[J]. Oncol Rep, 2017, 37(1):77-82.
[12]赵欣,纪志刚.一种新的循环肿瘤细胞检测平台在膀胱癌诊疗中的初步应用[J].癌症进展, 2017, 15(10):1142-1144; 1199.
[13]孙建兵,汪亚辉,马凯,等.循环肿瘤细胞检测技术及其在肿瘤侵袭转移中的研究进展[J].医学综述, 2018, 24(23):4652-4657.
[14] Niclolazzo C, Busetto GM, Del Giudice F, et al. The longterm prognostic value of survivin expressing circulating tumor cells in patients with high-risk non-muscle invasive bladder cancer(NMIBC)[J]. J Cancer Res Clin Oncol,2017, 143(10):1971-1976.
[15] Raimondi C, Gradilone A, Gazzaniga P. Circulating tumor cells in early bladder cancer:insight into micrometastatic disease[J]. Expert Rev Mol Diagn, 2014, 14(4):407-409.
[16] Busetto GM, Ferro M, Del Giudice F, et al. The prognostic role of circulating tumor cells(CTC)in high-risk non-muscle-invasive bladder cancer[J]. Clin Genitourin Cancer,2017, 15(4):e661-e666.
[17] Abrahamsson J, Aaltonen K, Engilbertsson H, et al. Circulating tumor cells in patients with advanced urothelial carcinoma of the bladder:association with tumor stage,lymph node metastases, FDG-PET findings, and survival[J]. Urol Oncol, 2017, 35(10):606.
[18] Todenh?fer T, Hennenlotter J, Dorner N, et al. Transcripts of circulating tumor cells detected by a breast cancer-specific platform correlate with clinical stage in bladder cancer patients[J]. J Cancer Res Clin Oncol, 2016, 142(5):1013-1020.
[19] Yin M, Joshi M, Meijer RP, et al. Neoadjuvant chemotherapy for muscle-invasive bladder cancer:a systematic review and two-step Meta-analysis[J]. Oncologist, 2016, 21(6):708-715.
[20] Msaouel P, Koutsilieris M. Diagnostic value of circulating tumor cell detection in bladder and urothelialcancer:systematic review and meta-analysis[J]. BMC Cancer, 2011,11:336.
[21] Gazzaniga P, Gradilone A, de Berardinis E, et al. Prognostic value of circulating tumor cells in nonmuscle invasive bladder cancer:a CellSearch analysis[J]. Ann Oncol,2012, 23(9):2352-2356.
[22] Vetterlein MW, Wankowicz SAM, Seisen T, et al. Neoadjuvant chemotherapy prior to radical cystectomy for muscleinvasivebladder cancer with variant histology[J]. Cancer,2017, 123(22):4346-4355.
[2]唐芮鹏. CTCs在膀胱癌转移及预后评估中的临床应用研究[D].昆明:昆明医科大学, 2017.
[3] Gorin MA, Verdone JE, van der Toom E, et al. Circulating tumour cells as biomarkers of prostate, bladder, and kidney cancer[J]. Nat Rev Urol, 2017, 14(2):90-97.
[4] Lima L, Neves M, Oliveira MI, et al. Sialyl-Tn identifies muscle-invasive bladder cancer basal and luminal subtypes facing decreased survival, being expressed by circulating tumor cells and metastases[J]. Urol Oncol, 2017, 35(12):675;e1; e8.
[5] Zhang Z, Fan W, Deng Q, et al. The prognostic and diagnostic value of circulating tumor cells in bladder cancer and upper tract urothelial carcinoma:a meta-analysis of 30 published studies[J]. Oncotarget, 2017, 8(35):59527-59538.
[6]那彦群,叶章群,孙光.中国泌尿外科疾病诊断治疗指南(2014版)[M].北京:人民卫生出版社, 2014:33-53.
[7] Zhang W, Xia W, Lv Z, et al. Liquid biopsy for cancer:circulating tumor cells, circulating free dna or exosomes?[J].Cell Physiol Biochem, 2017, 41(2):755-768.
[8]董建伟,夏凌,李攻科.循环肿瘤细胞富集技术研究进展[J].分析化学, 2018, 46(12):1851-1862.
[9] Politaki E, Agelaki S, Apostolaki S, et al. A comparison of three methods for the detection of circulating tumor cells in patients with early and metastatic breast cancer[J]. Cell Physiol Biochem, 2017, 44(2):594-606.
[10] Gabriel MT, Calleja LR, Chalopin A, et al. Circulating tumor cells:a review of non-EpCAM-based approaches for cell enrichment and isolation[J]. Clin Chem, 2016, 62(4):571-581.
[11] Chikaishi Y, Yoneda K, Ohnaga T, et al. EpCAM-independent capture of circulating tumor cells with a‘universal CTC-chip’[J]. Oncol Rep, 2017, 37(1):77-82.
[12]赵欣,纪志刚.一种新的循环肿瘤细胞检测平台在膀胱癌诊疗中的初步应用[J].癌症进展, 2017, 15(10):1142-1144; 1199.
[13]孙建兵,汪亚辉,马凯,等.循环肿瘤细胞检测技术及其在肿瘤侵袭转移中的研究进展[J].医学综述, 2018, 24(23):4652-4657.
[14] Niclolazzo C, Busetto GM, Del Giudice F, et al. The longterm prognostic value of survivin expressing circulating tumor cells in patients with high-risk non-muscle invasive bladder cancer(NMIBC)[J]. J Cancer Res Clin Oncol,2017, 143(10):1971-1976.
[15] Raimondi C, Gradilone A, Gazzaniga P. Circulating tumor cells in early bladder cancer:insight into micrometastatic disease[J]. Expert Rev Mol Diagn, 2014, 14(4):407-409.
[16] Busetto GM, Ferro M, Del Giudice F, et al. The prognostic role of circulating tumor cells(CTC)in high-risk non-muscle-invasive bladder cancer[J]. Clin Genitourin Cancer,2017, 15(4):e661-e666.
[17] Abrahamsson J, Aaltonen K, Engilbertsson H, et al. Circulating tumor cells in patients with advanced urothelial carcinoma of the bladder:association with tumor stage,lymph node metastases, FDG-PET findings, and survival[J]. Urol Oncol, 2017, 35(10):606.
[18] Todenh?fer T, Hennenlotter J, Dorner N, et al. Transcripts of circulating tumor cells detected by a breast cancer-specific platform correlate with clinical stage in bladder cancer patients[J]. J Cancer Res Clin Oncol, 2016, 142(5):1013-1020.
[19] Yin M, Joshi M, Meijer RP, et al. Neoadjuvant chemotherapy for muscle-invasive bladder cancer:a systematic review and two-step Meta-analysis[J]. Oncologist, 2016, 21(6):708-715.
[20] Msaouel P, Koutsilieris M. Diagnostic value of circulating tumor cell detection in bladder and urothelialcancer:systematic review and meta-analysis[J]. BMC Cancer, 2011,11:336.
[21] Gazzaniga P, Gradilone A, de Berardinis E, et al. Prognostic value of circulating tumor cells in nonmuscle invasive bladder cancer:a CellSearch analysis[J]. Ann Oncol,2012, 23(9):2352-2356.
[22] Vetterlein MW, Wankowicz SAM, Seisen T, et al. Neoadjuvant chemotherapy prior to radical cystectomy for muscleinvasivebladder cancer with variant histology[J]. Cancer,2017, 123(22):4346-4355.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |