Chen Fangfang, Ren Ping, Feng Ye, Liu Haiyan, Sun Yang, Liu Zhonghui, Ge Jingyan, Cui Xueling
Department of Gastrointestinal Surgery, China-Japan Union Hospital, Jilin University, Changchun, China.
Department of Thoracic Surgery, First Hospital of Jilin University, Changchun, China.
PLoS One. 2014 Oct 27;9(10):e111398. doi: 10.1371/journal.pone.0111398. eCollection 2014.
Follistatin (FST), a single chain glycoprotein, is originally isolated from follicular fluid of ovary. Previous studies have revealed that serum FST served as a biomarker for pregnancy and ovarian mucinous tumor. However, whether FST can serve as a biomarker for diagnosis in lung adenocarcinoma of humans remains unclear.
The study population consisted of 80 patients with lung adenocarcinoma, 40 patients with ovarian adenocarcinoma and 80 healthy subjects. Serum FST levels in patients and healthy subjects were measured using ELISA. The results showed that the positive ratio of serum FST levels was 51.3% (41/80), which was comparable to the sensitivity of FST in 40 patients with ovarian adenocarcinoma (60%, 24/40) using the 95th confidence interval for the healthy subject group as the cut-off value. FST expressions in lung adenocarcinoma were examined by immunohistochemical staining, we found that lung adenocarcinoma could produce FST and there was positive correlation between the level of FST expression and the differential degree of lung adenocarcinoma. Furthermore, the results showed that primary cultured lung adenocarcinoma cells could secrete FST, while cells derived from non-tumor lung tissues almost did not produce FST. In addition, the results of CCK8 assay and flow cytometry showed that using anti-FST monoclonal antibody to neutralize endogenous FST significantly augmented activin A-induced lung adenocarcinoma cells apoptosis.
These data indicate that lung adenocarcinoma cells can secret FST into serum, which may be beneficial to the survival of adenocarcinoma cells by neutralizing activin A action. Thus, FST can serve as a promising biomarker for diagnosis of lung adenocarcinoma and a useful biotherapy target for lung adenocarcinoma.
卵泡抑素(FST)是一种单链糖蛋白,最初从卵巢卵泡液中分离出来。先前的研究表明,血清FST可作为妊娠和卵巢黏液性肿瘤的生物标志物。然而,FST是否可作为人类肺腺癌诊断的生物标志物仍不清楚。
研究人群包括80例肺腺癌患者、40例卵巢腺癌患者和80名健康受试者。采用酶联免疫吸附测定法(ELISA)检测患者和健康受试者血清FST水平。结果显示,血清FST水平的阳性率为51.3%(41/80),以健康受试者组的第95百分位数作为临界值时,该阳性率与40例卵巢腺癌患者中FST的敏感性(60%,24/40)相当。通过免疫组织化学染色检测肺腺癌中FST的表达,我们发现肺腺癌可产生FST,且FST表达水平与肺腺癌的分化程度呈正相关。此外,结果表明原代培养的肺腺癌细胞可分泌FST,而非肿瘤肺组织来源的细胞几乎不产生FST。另外,CCK8检测和流式细胞术结果显示,使用抗FST单克隆抗体中和内源性FST可显著增强激活素A诱导的肺腺癌细胞凋亡。
这些数据表明,肺腺癌细胞可将FST分泌到血清中,这可能通过中和激活素A的作用而有利于腺癌细胞的存活。因此,FST可作为一种有前景的肺腺癌诊断生物标志物以及肺腺癌的有效生物治疗靶点。