Prostasin, a potential serum marker for ovarian cancer: Identification through microarray technology
Prostasin, a potential serum marker for ovarian cancer: Identification through microarray technology
复制标题
DOI：
10.1093/jnci/93.19.1458
复制
发表时间：
2001-10-03
期刊：
影响因子：
--
通讯作者：
Cramer, DW
中科院分区：
文献类型：
--
作者：
Mok, SC;Chao, J;Cramer, DW
背景：卵巢癌的诊断较晚，生存率较低，因此需要筛选卵巢癌的生物标志物。我们使用微阵列技术来确定分泌蛋白的高表达基因作为潜在的血清生物标志物，并选择前列腺素，一种通常由前列腺分泌的丝氨酸蛋白酶，用于进一步研究。方法：从3个卵巢癌细胞系和3个正常人卵巢表面上皮细胞系中分离和融合RNA。从这些池中产生的互补DNA被杂交到微阵列载玻片上，并鉴定了癌细胞中过度表达的基因。实时荧光定量聚合酶链式反应检测前列腺素基因在卵巢癌和Hose细胞系中的表达。应用抗前列腺素抗体检测卵巢癌患者前列腺素的表达，并用双抗体夹心法测定血清前列腺素水平。先前测定的卵巢癌标记物CA125水平可从所有受试者中获得约70%。所有的统计检验都是双面的。结果：前列腺素在卵巢癌上皮细胞和间质中的表达强于正常卵巢组织。经年龄、采集年限和标本质量调整后，卵巢癌患者血清前列腺素平均水平为13.7mug/mL(95%可信区间为10.5~16.9mug/mL)，对照组为7.5mug/mL(95%CI=6.6~8.3mug/mL)。16例术前术后均采血的患者中，14例术后前列腺素水平显著低于术前水平(P=0.004)。在37例非粘液性卵巢癌患者和100例正常对照中，CA125和前列腺素联合检测卵巢癌的敏感性为92%(95%CI=78.1%~98.3%)，特异性为94%(95%CI=87.4%~97.7%)。结论：前列腺素在上皮性卵巢癌中高表达，应作为筛查或肿瘤标志物，单独或联合CA125进行进一步研究。
Background: Screening biomarkers for ovarian cancer are needed because of its late stage at diagnosis and poor survival. We used microarray technology to identify overexpressed genes for secretory proteins as potential serum biomarkers and selected prostasin, a serine protease normally secreted by the prostate gland, for further study. Methods: RNA was isolated and pooled from three ovarian cancer cell lines and from three normal human ovarian surface epithelial (HOSE) cell lines. Complementary DNA generated from these pools was hybridized to a microarray slide, and genes overexpressed in the cancer cells were identified. Real-time quantitative polymerase chain reaction was used to examine prostasin gene expression in ovarian cancer and HOSE cell lines. Anti-prostasin antibodies were used to examine prostasin expression and to measure serum prostasin by an enzyme-linked immunosorbent assay in 64 case patients with ovarian cancer and in 137 control subjects. Previously determined levels of CA 125, an ovarian cancer marker, were available from about 70% of all subjects. All statistical tests were two-sided. Results: Prostasin was detected by immunostaining more strongly in cancerous ovarian epithelial cells and stroma than in normal ovarian tissue. The mean level of serum prostasin was 13.7 mug/mL (95% confidence interval [CI] = 10.5 to 16.9 mug/mL) in 64 case patients with ovarian cancer and 7.5 mug/mL (95% CI = 6.6 to 8.3 mug/mL) in 137 control subjects (P < .041, after adjustment for the subject's age, year of collection, and specimen quality). In 14 of 16 case patients with both preoperative and postoperative serum samples, postoperative prostasin levels were statistically significantly lower than preoperative levels (P =.004). In 37 case patients with nonmucinous ovarian cancer and in 100 control subjects for whom levels of CA 125 and prostasin were available, the combination of markers gave a sensitivity of 92% (95% CI = 78.1% to 98.3%) and a specificity of 94% (95% CI = 87.4% to 97.7%) for detecting ovarian cancer. Conclusions: Prostasin is overexpressed in epithelial ovarian cancer and should be investigated further as a screening or tumor marker, alone and in combination with CA 125.