Grimaldi Franco, Vescini Fabio, Tonelli Veronica, Pistis Cinzia, Kara Elda, Triggiani Vincenzo, Tonutti Elio, Curcio Francesco, Fabris Martina
Endocrinology and Metabolism Unit, University Hospital of Udine, Udine, Italy.
Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
Endocr Metab Immune Disord Drug Targets. 2018;18(6):618-625. doi: 10.2174/1871530318666180529111224.
BLyS (B-Lymphocyte stimulator) is over-expressed in several tumoral settings, with direct or indirect effects on neoplastic proliferation and possibly representing a therapeutic target. In this study, we explored the role of BLyS in a large population of patients with neuroendocrine tumors (NETs).
The study analyzed the stored sera of 124 consecutive unselected patients with NETs: 36 lung carcinoids (24 typical, 12 atypical), 47 gastroenteric tract and 41 pancreatic (30 non-functioning and 11 functioning: 9 insulinomas, 2 glucagonomas). In 23 cases, BLyS was repeatedly assessed during the follow-up and the disease was monitored (progression, stabilization or remission) according to the RECIST criteria. Patients were compared to 92 age and sex-matched blood donors (BDs). Serum levels of BLyS and Chromogranin A (CgA) were analyzed by ELISA.
NET patients showed significantly higher BLyS levels than BDs (1274±809 pg/ml vs. 587±173 pg/ml; p<0.0001). BLyS correlated weakly with CgA (r=0.19 and p=0.035) but did not correlate with Ki67, grading, metastasis, histological type and site. In patients with sustained remission after surgery, BLyS and CgA both showed a gradual reduction over time. Patients with progressing disease showed higher BLyS levels compared to stable patients (1524±694 pg/ml vs. 1168± 373 pg/ml; p= 0.033). BLyS serum levels remained stable in remission and therapy-controlled patients, while increased in the follow-up of progressing cases.
Higher BLyS levels identify patients with a more severe disease, characterized by progression despite treatments, possibly representing a factor implicated in the proliferation of the neoplastic cells or in sustaining the neoplastic environment.
B淋巴细胞刺激因子（BLyS）在多种肿瘤环境中过度表达，对肿瘤增殖有直接或间接影响，可能是一个治疗靶点。在本研究中，我们探讨了BLyS在大量神经内分泌肿瘤（NETs）患者中的作用。
该研究分析了124例连续入选的未经选择的NETs患者的储存血清：36例肺类癌（24例典型，12例非典型），47例胃肠道和41例胰腺（30例无功能，11例有功能：9例胰岛素瘤，2例胰高血糖素瘤）。在23例患者中，随访期间反复评估BLyS，并根据RECIST标准监测疾病（进展、稳定或缓解）。将患者与92例年龄和性别匹配的献血者（BDs）进行比较。通过ELISA分析血清BLyS和嗜铬粒蛋白A（CgA）水平。
NET患者的BLyS水平显著高于BDs（1274±809 pg/ml对587±173 pg/ml；p<0.0001）。BLyS与CgA弱相关（r=0.19，p=0.035），但与Ki67、分级、转移、组织学类型和部位无关。术后持续缓解的患者中，BLyS和CgA均随时间逐渐降低。疾病进展的患者与病情稳定的患者相比，BLyS水平更高（1524±694 pg/ml对1168±373 pg/ml；p=0.033）。缓解期和治疗控制期患者的BLyS血清水平保持稳定，而进展期病例随访期间升高。
较高的BLyS水平可识别疾病更严重的患者，其特征为尽管接受治疗仍进展，可能代表与肿瘤细胞增殖或维持肿瘤环境有关的一个因素。
