SERUM INTERLEUKIN-6 LEVELS CORRELATE WITH DISEASE STATUS IN PATIENTS WITH EPITHELIAL OVARIAN-CANCER
SERUM INTERLEUKIN-6 LEVELS CORRELATE WITH DISEASE STATUS IN PATIENTS WITH EPITHELIAL OVARIAN-CANCER
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DOI：
10.1016/0002-9378(91)90582-c
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发表时间：
1991-04-01
影响因子：
9.8
通讯作者：
MARTINEZMAZA, O
中科院分区：
文献类型：
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作者：
BEREK, JS;CHUNG, C;MARTINEZMAZA, O
白细胞介素-6是一种多效性细胞因子，具有广泛的作用，包括诱导B细胞和细胞毒性T细胞分化，以及诱导肝细胞产生急性期反应物。 白细胞介素-6在恶性肿瘤中也可作为自分泌生长因子。 多种细胞类型产生白细胞介素-6，包括T和B细胞、单核细胞、成纤维细胞和一些实体瘤细胞。 在以前的工作中，我们检测到大量的白细胞介素-6的生产的人卵巢癌细胞，包括卵巢癌细胞系CAOV-3，OVCAR-3，SKOV-3，和几个主要的卵巢肿瘤培养物。 在这项研究中，我们回顾性地检测了36例上皮性卵巢癌患者的90份血清标本中的白细胞介素-6。 这些具有肉眼可见疾病的卵巢癌患者（n = 57）的平均血清白细胞介素-6浓度为0.26 +/- 0.04 U/ml（平均值+/- SEM）。 健康成人供体的白细胞介素-6血清水平为0.12 +/- 0.03 U/ml。 21例卵巢癌患者中有16例（76%）血清白细胞介素-6水平升高（> 0.20 U/ml），部分患者接近1 U/ml（p < 0.01）。 在9例巨大肿瘤（残留> 2 cm）患者中，8例（89%）白细胞介素-6水平升高（平均0.31 ± 0.05），而12例微小残留肿瘤（<2 cm）患者中有8例（66%）白细胞介素-6水平升高。 15例临床缓解和显微镜下病变患者中只有2例（13%）数值升高。 在36例患者中，22例为CA 125阴性（< 35 U/ml），其中4例白细胞介素-6水平升高。 在14例CA 125水平升高的患者中，12例（86%）白细胞介素6水平升高。 在这16名患者中，连续测量白细胞介素-6水平，发现9名（56%）患者的白细胞介素-6水平在3至4个月的时间间隔内升高;这与肿瘤进展相关。 此外，患者的后续生存期与白细胞介素-6水平相关，例如白细胞介素-6水平升高> 0.20 U/ml的患者平均存活12.5个月，而白细胞介素-6水平正常的患者平均存活27.2个月（p < 0.001）。 这些数据支持白细胞介素-6可能是某些上皮性卵巢癌患者的有用肿瘤标志物的概念，因为它与肿瘤负荷、临床疾病状态和生存率相关。
Interleukin-6 is a pleiotropic cytokine with a wide range of effects, including induction of B-cell and cytotoxic T-cell differentiation, and induction of acute phase reactant production by hepatocytes. Interleukin-6 also can act as an autocrine growth factor in malignancy. Various cell types produce interleukin-6, including T and B cells, monocytes, fibroblasts, and some solid tumor cells. In previous work we detected the production of substantial amounts of interleukin-6 by human ovarian cancer cells, including the ovarian cancer cell lines CAOV-3, OVCAR-3, and SKOV-3, and several primary ovarian tumor cultures. In this study we retrospectively examined 90 separate serum specimens for interleukin-6 in 36 patients with epithelial ovarian cancer. The mean serum interleukin-6 concentration of those ovarian cancer patients with macroscopic disease (n = 57) was 0.26 +/- 0.04 U/ml (mean +/- SEM). Healthy adult donors have interleukin-6 serum levels of 0.12 +/- 0.03 U/ml. Sixteen of 21 ovarian cancer patients with macroscopic disease (76%) had elevated (> 0.20 U/ml) levels of serum interleukin-6, with levels approaching 1 U/ml in some patients (p < 0.01). Of those nine patients with bulky tumor (residual > 2 cm), eight (89%) had an elevated interleukin-6 level (mean, 0.31 +/- 0.05), while eight of 12 (66%) with minimal residual disease (< 2cm) had elevated levels. Only two of 15 (13%) patients who were in clinical remission and who had microscopic disease had elevated values. Of the 36 patients, 22 were CA 125 negative (< 35 U/ml), and of these, four had elevated interleukin-6 levels. Of the 14 patients with an elevated CA 125 level, 12 (86%) had elevated interleukin-6 levels. In those 16 patients in whom serial levels of interleukin-6 were measured, rising levels were found over a 3 to 4 month interval in nine (56%); this correlated with tumor progression. Furthermore, the subsequent survival of patients was shown to correlate with the level of interleukin-6, such that patients whose levels were elevated > 0.20 U/ml interleukin-6 survived a mean of 12.5 months, compared with 27.2 months for patients with normal levels (p < 0.001). These data support the concept the interleukin-6 may be a useful tumour marker in some patients with epithelial overain cancer, as it correlates with the tumor burden, clinical disease status, and survival.