CTCs在膀胱癌转移及预后评估中应用的研究

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目的检测膀胱癌患者外周血循环肿瘤细胞(circulating tumor cells,CTCs)的计数及分型,研究其在膀胱癌的转移及预后评估中的临床应用价值。方法采用CanPatrolTM二代CTCs检测技术检测外周血CTCs计数及分型。41例经病理确诊的膀胱癌患者纳入研究,患者年龄33~83岁,男37例,女4例。肿瘤TNM分期:T1期15例、T2期12例、T3期9例、T4期5例、N1期6例、M1期3例。肿瘤组织病理分级:高级别膀胱癌30例、低级别膀胱癌11例。结果 41例膀胱癌患者总CTCs阳性率为68.29%(28/41),6例淋巴结转移患者中检出CTCs阳性2例,3例远处转移患者中检出CTCs阳性1例。本研究共检出CTCs 136个,其中上皮型CTCs 36个(26.5%)、混合型CTCs 70个(51.5%)、间质型CTCs 30个(22.0%);间质化CTCs 100个,占73.5%。30例高级别膀胱癌中CTCs检出20例,占66.7%,11例低级别膀胱癌中CTCs检出7例,占63.6%。13例CTCs阴性患者中,无淋巴结转移10例(69.23%),淋巴结转移3例(30.76%)。T1G3患者间质型CTCs阳性率为60.0%,CTCs总数≥3的患者比例为60.0%;T1G1~2患者间质型CTCs阳性率为20.0%,CTCs总数≥3的患者比例为20.0%。41例中29例患者术后获得随访,随访12~41个月,平均(13±2)个月,死亡8例。术后总生存率为72.41%,其中CTCs阳性者生存率为77.77%(14/18),CTCs阴性者生存率为63.60%(7/11)。结论 T1G3患者的间质型CTCs阳性率及CTCs总数≥3的患者比例明显高于T1G1~2患者。CTCs的总数及间质型CTCs的个数能够在一定程度上预测膀胱癌的恶性程度,并指导非肌层浸润性膀胱癌患者的早期治疗。CTCs的阳性检出率与膀胱癌的TNM分期、淋巴结转移、近期生存率之间未发现有明显相关性。 Objective To test the counting and typing of circulating tumor cells (CTCs) in patients with bladder cancer, and to investigate its clinical value in the metastasis and prognosis evaluation of bladder cancer. Methods The CTCs count and typing of peripheral blood were detected by CanPatrolTM second generation CTCs detection technique. 41 cases of pathologically diagnosed bladder cancer patients included in the study, patients aged 33 to 83 years, 37 males and 4 females. TNM staging of tumor: T1 in 15 cases, T2 in 12 cases, T3 in 9 cases, T4 in 5 cases, N1 in 6 cases, M1 in 3 cases. Tumor tissue pathological grade: 30 cases of high-grade bladder cancer, 11 cases of low-grade bladder cancer. Results The positive rate of total CTCs in 41 cases of bladder cancer was 68.29% (28/41). Two cases of positive CTCs were detected in 6 cases of lymph node metastasis and one case of CTCs was positive in 3 cases of distant metastasis. A total of 136 CTCs were detected in this study, including 36 epithelial CTCs (26.5%), 70 mixed CTCs (51.5%), 30 interstitial CTCs (22.0%) and 100 interstitial CTCs (73.5% %. CTCs were detected in 30 cases of high-grade bladder cancer in 20 cases, accounting for 66.7%. In 11 cases of low-grade bladder cancer, CTCs were detected in 7 cases (63.6%). Thirteen patients with negative CTCs had no lymph node metastasis in 10 patients (69.23%) and 3 lymph node metastases (30.76%). The positive rate of CTCs in patients with T1G3 was 60.0% and the percentage of patients with CTCs ≥3 was 60.0%. The positive rate of interstitial CTCs was 20.0% in T1G1 patients and 20.0% in patients with CTCs ≥3. Twenty-one of 41 patients were followed up for 12 to 41 months with an average of (13 ± 2) months and 8 died. The overall survival rate was 72.41%. The survival rate of patients with positive CTCs was 77.77% (14/18), and the survival rates of patients with negative CTCs were 63.60% (7/11). Conclusion The positive rate of interstitial CTCs in patients with T1G3 and the total number of CTCs≥3 are significantly higher than those in T1G1 ~ 2 patients. The total number of CTCs and the number of interstitial CTCs can predict the degree of malignancy of bladder cancer to a certain extent and guide the early treatment of patients with non-muscle invasive bladder cancer. No positive correlation was found between the positive detection rate of CTCs and the TNM stage of bladder cancer, lymph node metastasis and recent survival rate.
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