PO.CL01.22 · 临床研究
前列腺癌患者中过表达PD-L1并伴有细胞簇的循环肿瘤细胞
Over expressing PD-L1 circulating tumor cells with clusters in prostate cancer patients
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：
由于包括PSA检测在内的现有筛查方法特异性和敏感性有限，前列腺癌（PC）的检测仍具有挑战性。然而，PSA无法区分侵袭性疾病与惰性疾病，导致过度诊断和过度治疗。相比之下，循环肿瘤细胞（CTCs）提供更大的临床价值，因为它们可实时反映肿瘤生物学、疾病进展和治疗反应。与PSA不同，CTCs是一种动态生物标志物，可提示全身性微小细胞残留病灶（MCRD），有助于监测和指导个体化前列腺癌管理。此外，CTCs上PD-L1的过表达可揭示免疫逃逸机制，并可能在PC中具有预测和预后价值。我们报告了PC患者中CTC的捕获及其PD-L1阳性和细胞簇情况。
方法：
回顾性分析了239例前列腺癌患者的CTC-PD-L1和CTC细胞簇的存在情况，包括216例（90.4%）基线样本和23例（9.6%）随访样本。使用经CDSCO（印度）批准的OncoDiscover Test，采用基于抗EpCAM抗体的免疫磁富集法从1.5 ml血液中分离CTCs。CTCs被鉴定为CK18⁺/DAPI⁺/CD45⁻、PD-L1表达⁺且具有独特形态的细胞。自动荧光成像量化信号强度，以与临床病理参数相关联。患者按年龄分层，并对CTC阳性率、PD-L1表达和细胞簇频率进行定量分析。
结果：
173例（72.4%）患者检测到CTCs，66例（27.6%）为阴性。在157例可评估PD-L1的样本中，131例（54.8%）为PD-L1阳性，26例（10.9%）为阴性。19例（11%）患者观察到CTC细胞簇，而154例患者（89%）仅有单个CTCs。基线时70.4%的患者可检测到CTCs，随访时增至91.3%。而CTC-PD-L1阳性率在基线时为52.3%，随访时为85.7%。此外，PD-L1阳性CTC细胞簇从基线时的10.5%增至随访时的13.1%。主要年龄组为61-70岁（39.0%）和71-80岁（39.9%），二者合计近占队列的80%。每例患者CTC计数的平均分布为1.14，PD-L1阳性CTCs为0.95，CTC细胞簇为0.12。
结论：
前列腺癌患者中观察到CTCs和PD-L1表达的高流行率，尤其在较年长年龄组中。PD-L1阳性CTCs的检出凸显了确证性MCRD的存在以及循环中疾病的存在。CTC细胞簇的相对低发生率提示集体迁移有限，尽管其存在可能预示更具侵袭性的疾病表型。
查看英文原文 English abstract
Background:
Prostate cancer (PC) detection remains challenging due to the limited specificity and sensitivity of current screening methods, including PSA testing. However doesn't distinguish aggressiveness from indolent disease, leading to overdiagnosis and overtreatment. Circulating Tumor Cells (CTCs), however, offer greater clinical value as they provide real-time insights into tumor biology, disease progression, and treatment response. Unlike PSA, CTCs represents a dynamic biomarker implicating minimal cellular residual disease (MCRD) systemically, helpful for monitoring and guiding the personalized prostate cancer management. In addition, the over- expression of PD-L1 on CTCs provides insights into immune evasion mechanisms and may have predictive and prognostic value in PC. We report CTC capture, having PD-L1 positivity and clusters, in PC patients.
Methods:
Retrospectively, 239 prostate cancer patients were analysed for presence of CTC-PD-L1 and CTC clusters, including 216 (90.4%) baseline and 23 (9.6%) follow-up samples. CTCs were isolated using the CDSCO-approved (India) OncoDiscover Test employing anti EpCAM antibody-based immunomagnetic enrichment / 1.5 ml of blood. CTCs were identified as CK18⁺/DAPI⁺/CD45⁻, PD-L1 expression⁺ cells with distinct morphology. Automated fluorescence imaging quantified signal intensities to correlate with clinicopathological parameters. Patients were stratified for age, and quantitative analysis of CTC positivity, PD-L1 expression, and cluster frequency was performed.
Results:
CTCs were detected in 173 (72.4%) patients, while 66 (27.6%) were negative. Amongst 157 evaluable samples for PD-L1, 131 (54.8%) were PD-L1 positive and 26 (10.9%) were negative. CTC clusters were observed in 19 (11%) patients, while 154 patients (89%) had only single CTCs. At baseline, CTCs were detectable in 70.4% of patients, increased to 91.3% at follow-up patients. While, CTC-PD-L1 positivity was observed in 52.3% patients at baseline and 85.7% in follow-up. Additionally, PD-L1-positive CTC clusters increased from 10.5% at baseline to 13.1% at follow-up. The predominant age groups were 61-70 years (39.0%) and 71-80 years (39.9%), together comprising nearly 80% of the cohort. The mean distribution of CTC counts per patient were 1.14, 0.95 for CTCs with PD-L1, and 0.12 for CTC clusters.
Conclusion:
A high prevalence of CTCs and PD-L1 expression was observed among prostate cancer patients, particularly in older age groups. The detection of PD-L1 +ve CTCs highlights the presence of confirmative MCRD, and presence of disease in circulation. The relatively low incidence of CTC clusters suggests limited collective migration, although their presence may signify more aggressive disease phenotypes.
利益披露 Disclosure
J. Khandare,
Actorius Patent, Cofounder.
B. Bhosale, None.
G. Aland,
Actorius Employment.
S. Jayant,
Actorius Employment.
A. Ashturkar,
Actorius Employment.
V. Jadhav, None..
A. Joshi, None..
S. Mishra, None..
P. Kendre, None.
A. Vasudevan,
Actorius Employment.
V. Maniar, None..
J. Kulkarni, None.