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免疫功能障碍的增加与基质金属蛋白酶-2 表达的增加相关,并可预测骨髓微转移阳性局限性前列腺癌患者的生化失败。

Increasing Immune Dysfunction is Associated with Increasing Matrix-Metalloproteinase-2 Expression and Predicts Biochemical Failure in Men with Bone Marrow Micro-Metastasis Positive Localized Prostate Cancer.

机构信息

CTC Unit, Faculty of Medicine, University Finis Terrae, Santiago, Chile.

Faculty of Medicine, University Finis Terrae Santiago, Chile.

出版信息

Asian Pac J Cancer Prev. 2022 Jul 1;23(7):2497-2505. doi: 10.31557/APJCP.2022.23.7.2497.

DOI:10.31557/APJCP.2022.23.7.2497
PMID:35901359
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9727333/
Abstract

INTRODUCTION

To determine if there was an association of the ALC (absolute lymphocyte count) and LCP (lymphocytopenia) with the expression of MMP-2 in bone marrow micro-metastasis, the changes occurring during follow-up and association with biochemical failure.

METHODS AND PATIENTS

One month after surgery blood and bone marrow samples were taken to determine the presence of micro-metastasis, the presence of circulating prostate cells (CPCs) and ALC. CPCs and micro-metastasis were detected using immunocytochemistry and MMP-2 expression determined in micro-metastasis. Only men positive for micro-metastasis participated in the study. At end follow blood was taken for serum PSA, ALC and CPCs, if the ALC decreased by more than 10% bone marrow sampling was repeated and MMP-2 expression determined, similarly for men with BF. Men who had stable ALCs had an end of study evaluation of the bone marrow.

RESULTS

402 men underwent radical prostatectomy, one month post surgery 79 men were positive for only bone marrow micro-metastasis and formed the study group; of whom 36/79 (45%) underwent BF. Clinical pathological findings were not significantly different between men with or without BF. In men with BF the ALC was significantly lower one-month post surgery. The 5 and 10 year Kaplan-Meier survival was 100% at 5-years and 65% at 10-years for the whole cohort. Men without BF had stable ALCs. A decrease of >10% in the ALC was associated with increasing MMP-2 expression in the micro-metastasis and surrounding stromal tissue, the appearance of CPCs 6-12 months later and BF.

CONCLUSIONS

the immune host-tumour cell interaction in the microenvironment is dynamic and changes with time. A decreasing ALC may be a valuable marker in identifying men with high risk of BF and changes in immune mediated dormancy before the PSA rises.

摘要

简介

为了确定绝对淋巴细胞计数(ALC)和淋巴细胞减少症(LCP)与骨髓微转移中 MMP-2 的表达是否存在关联,以及在随访期间的变化及其与生化失败的关系。

方法和患者

手术后一个月采集血液和骨髓样本,以确定微转移、循环前列腺细胞(CPCs)和 ALC 的存在。使用免疫细胞化学检测 CPCs 和微转移,在微转移中确定 MMP-2 的表达。只有微转移阳性的男性参与了这项研究。在随访结束时,采集血液进行血清 PSA、ALC 和 CPCs 检测,如果 ALC 下降超过 10%,则重复骨髓取样并确定 MMP-2 的表达,对于 BF 男性也是如此。ALC 稳定的男性在研究结束时对骨髓进行评估。

结果

402 名男性接受了根治性前列腺切除术,术后一个月,79 名男性仅骨髓微转移阳性,形成研究组;其中 36/79(45%)发生 BF。有或没有 BF 的男性的临床病理发现无显著差异。在发生 BF 的男性中,术后一个月的 ALC 明显较低。整个队列的 5 年和 10 年 Kaplan-Meier 生存率为 100%,5 年为 65%。没有 BF 的男性 ALC 稳定。ALC 下降超过 10%与微转移和周围基质组织中 MMP-2 表达增加、6-12 个月后 CPCs 的出现以及 BF 相关。

结论

微环境中免疫宿主-肿瘤细胞相互作用是动态的,会随时间而变化。ALC 下降可能是识别 BF 风险高的男性和 PSA 升高前免疫介导休眠变化的有价值的标志物。

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The expression of matrix-metalloproteinase-2 in bone marrow micro-metastasis is associated with the presence of circulating prostate cells and a worse prognosis in men treated with radical prostatectomy for prostate cancer.基质金属蛋白酶-2在骨髓微转移中的表达与循环前列腺细胞的存在以及接受前列腺癌根治术治疗的男性患者预后较差有关。
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Neutrophil-to-lymphocyte ratio may be associated with the outcome in patients with prostate cancer.中性粒细胞与淋巴细胞比值可能与前列腺癌患者的预后相关。
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