Khan Ghazala, Brooks Suzanne E, Mills Ken I, Guinn Barbara-Ann
Department of Life Sciences, University of Bedfordshire, Park Square, Luton, Bedfordshire, UK.
Biomedical Imaging Unit, Southampton General Hospital, Southampton, UK.
Biomark Cancer. 2015 Aug 16;7:31-8. doi: 10.4137/BIC.S28378. eCollection 2015.
Ovarian cancer is very treatable in the early stages of disease; however, it is usually detected in the later stages, at which time, treatment is no longer as effective. If discovered early (Stage I), there is a 90% chance of five-year survival. Therefore, it is imperative that early-stage biomarkers are identified to enhance the early detection of ovarian cancer. Cancer-testis antigens (CTAs), such as Per ARNT SIM (PAS) domain containing 1 (PASD1), are unique in that their expression is restricted to immunologically restricted sites, such as the testis and placenta, which do not express MHC class I, and cancer, making them ideally positioned to act as targets for immunotherapy as well as potential biomarkers for cancer detection where expressed. We examined the expression of PASD1a and b in a number of cell lines, as well as eight healthy ovary samples, eight normal adjacent ovarian tissues, and 191 ovarian cancer tissues, which were predominantly stage I (n = 164) and stage II (n = 14) disease. We found that despite the positive staining of skin cancer, only one stage Ic ovarian cancer patient tissue expressed PASD1a and b at detectable levels. This may reflect the predominantly stage I ovarian cancer samples examined. To examine the restriction of PASD1 expression, we examined endometrial tissue arrays and found no expression in 30 malignant tumor tissues, 23 cases of hyperplasia, or 16 normal endometrial tissues. Our study suggests that the search for a single cancer-testes antigen/biomarker that can detect early ovarian cancer must continue.
卵巢癌在疾病早期是非常可治的;然而,它通常在晚期才被检测到,此时治疗效果就不再那么好了。如果早期发现(I期),五年生存率有90%。因此,识别早期生物标志物以提高卵巢癌的早期检测至关重要。癌-睾丸抗原(CTAs),如含Per ARNT SIM(PAS)结构域1(PASD1),其独特之处在于它们的表达仅限于免疫受限部位,如睾丸和胎盘,这些部位不表达MHC I类分子,以及癌症组织,这使得它们非常适合作为免疫治疗的靶点以及在其表达时用于癌症检测的潜在生物标志物。我们检测了PASD1a和b在多种细胞系、8个健康卵巢样本、8个正常相邻卵巢组织以及191个卵巢癌组织中的表达,这些卵巢癌组织主要为I期(n = 164)和II期(n = 14)疾病。我们发现,尽管皮肤癌呈阳性染色,但只有1例Ic期卵巢癌患者组织能检测到PASD1a和b的表达。这可能反映了所检测的主要为I期卵巢癌样本。为了研究PASD1表达受限制的情况,我们检测了子宫内膜组织芯片,发现在30个恶性肿瘤组织、23例增生组织或16个正常子宫内膜组织中均无表达。我们的研究表明,寻找一种能够检测早期卵巢癌的单一癌-睾丸抗原/生物标志物的工作必须继续。