循环中的程序性死亡蛋白1（PD-1）、程序性死亡配体1（PD-L1）、嗜乳脂蛋白3A1（BTN3A1）、泛嗜乳脂蛋白3A（pan-BTN3As）、嗜乳脂蛋白2A1（BTN2A1）和B和T淋巴细胞衰减蛋白（BTLA）水平能否增强晚期高级别浆液性卵巢癌患者中糖类抗原125（CA125）的预后预测能力？
Can circulating PD-1, PD-L1, BTN3A1, pan-BTN3As, BTN2A1 and BTLA levels enhance prognostic power of CA125 in patients with advanced high-grade serous ovarian cancer?
作者信息
Fanale Daniele, Corsini Lidia Rita, Brando Chiara, Cutaia Sofia, Di Donna Mariano Catello, Filorizzo Clarissa, Lisanti Maria Chiara, Randazzo Ugo, Magrin Luigi, Romano Raffaella, Bazan Russo Tancredi Didier, Olive Daniel, Vieni Salvatore, Pantuso Gianni, Chiantera Vito, Russo Antonio, Bazan Viviana, Iovanna Juan Lucio
机构信息
Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
Department of Gynecologic Oncology, University of Palermo, Palermo, Italy.
出版信息
Front Oncol. 2022 Sep 21;12:946319. doi: 10.3389/fonc.2022.946319. eCollection 2022.
The most common subtype of ovarian cancer (OC) is the high-grade serous ovarian carcinoma (HGSOC), accounting for 70%-80% of all OC deaths. Although HGSOC is a potentially immunogenic tumor, clinical studies assessing the effectiveness of inhibitors of programmed death protein and its ligand (PD-1/PD-L1) in OC patients so far showed only response rates <15%. However, recent studies revealed an interesting prognostic role of plasma PD-1/PD-L1 and other circulating immunoregulatory molecules, such as the B- and T-lymphocyte attenuator (BTLA), butyrophilin sub-family 3A/CD277 receptors (BTN3A), and butyrophilin sub-family 2 member A1 (BTN2A1), in several solid tumors. Since evidence showed the prognostic relevance of pretreatment serum CA125 levels in OC, the aim of our study was to investigate if soluble forms of inhibitory immune checkpoints can enhance prognostic power of CA125 in advanced HGSOC women. Using specific ELISA tests, we examined the circulating PD-1, PD-L1, pan-BTN3As, BTN3A1, BTN2A1, and BTLA levels in 100 advanced HGSOC patients before treatment, correlating them with baseline serum CA125, age at diagnosis, body mass index (BMI), and peritoneal carcinomatosis. A multivariate analysis revealed that plasma BTN3A1 ≤4.75 ng/ml (HR, 1.94; 95% CI, 1.23-3.07; p=0.004), age at diagnosis ≤60 years (HR, 1.65; 95% CI, 1.05-2.59; p=0.03) and absence of peritoneal carcinomatosis (HR, 2.65; 95% CI, 1.66-4.22; p<0.0001) were independent prognostic factors for a longer progression-free survival (PFS) (≥30 months) in advanced HGSOC women. However, further two-factor multivariate analyses highlighted that baseline serum CA125 levels >401 U/ml and each soluble protein above respective concentration cutoff were covariates associated with shorter PFS (<30 months) and unfavorable clinical outcome, suggesting that contemporary measurement of both biomarkers than CA125 only could strengthen prognostic power of serum CA125 in predicting PFS of advanced HGSOC women. Plasma PD-L1, PD-1, BTN3A1, pan-sBTN3As, BTN2A1, or BTLA levels could be helpful biomarkers to increase prognostic value of CA125.
卵巢癌（OC）最常见的亚型是高级别浆液性卵巢癌（HGSOC），占所有OC死亡病例的70%-80%。尽管HGSOC是一种具有潜在免疫原性的肿瘤，但迄今为止评估程序性死亡蛋白及其配体（PD-1/PD-L1）抑制剂对OC患者有效性的临床研究显示，缓解率仅<15%。然而，最近的研究揭示了血浆PD-1/PD-L1以及其他循环免疫调节分子，如B和T淋巴细胞衰减器（BTLA）、嗜乳脂蛋白亚家族3A/CD277受体（BTN3A）和嗜乳脂蛋白亚家族2成员A1（BTN2A1），在几种实体瘤中具有有趣的预后作用。由于有证据表明预处理血清CA125水平在OC中具有预后相关性，我们研究的目的是调查抑制性免疫检查点的可溶性形式是否能增强CA125对晚期HGSOC女性的预后预测能力。我们使用特异性ELISA检测，检测了100例晚期HGSOC患者治疗前循环中的PD-1、PD-L1、泛BTN3A、BTN3A1、BTN2A1和BTLA水平，并将它们与基线血清CA125、诊断时年龄、体重指数（BMI）和腹膜转移情况进行关联分析。多因素分析显示，血浆BTN3A1≤4.75 ng/ml（HR，1.94；95%CI，1.23-3.07；p=0.004）、诊断时年龄≤60岁（HR，1.65；95%CI，1.05-2.59；p=0.03）以及无腹膜转移（HR，2.65；95%CI，1.66-4.22；p<0.0001）是晚期HGSOC女性无进展生存期（PFS）更长（≥30个月）的独立预后因素。然而，进一步的双因素多因素分析强调，基线血清CA125水平>401 U/ml以及每种可溶性蛋白高于各自浓度临界值是与较短PFS（<30个月）和不良临床结局相关的协变量，这表明同时测量这两种生物标志物而非仅测量CA125，可以增强血清CA125在预测晚期HGSOC女性PFS方面的预后预测能力。血浆PD-L1、PD-1、BTN3A1、泛可溶性BTN3A、BTN2A1或BTLA水平可能是有助于提高CA125预后价值的生物标志物。
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