卵巢高级别浆液性癌中PD-L2的表达及其临床意义

Expression and clinical significance of PD-L2 in high-grade serous ovarian carcinoma

目的探讨卵巢高级别浆液性癌(high-grade serous ovarian carcinoma,HGSOC)中PD-L2的表达及其临床意义。方法收集HGSOC临床资料,采用免疫组化EnVision法检测PD-L2、CD68、CD163的表达,并分析其与临床病理特征及预后的关系。结果HGSOC中肿瘤细胞(tumor cell,TC)和肿瘤浸润性免疫细胞(tumor-infiltrating immune cell,TIIC)PD-L2的阳性率分别为27.9%(17/61)、60.7%(37/61)。TC PD-L2阳性与一线含铂化疗反应性相关,其在铂耐药患者中的阳性率(58.3%,7/12)高于铂敏感患者中的阳性率(20.4%,10/49)(P=0.026),但TC PD-L2表达与患者年龄、术前血清CA125水平、肿瘤最大径、累及侧别、病理分期、手术满意度及腹水量均无关(P均>0.05)。TIIC PD-L2表达与患者年龄、术前血清CA125水平、肿瘤最大径、累及侧别、病理分期、手术满意度、腹水量及一线含铂化疗反应性均无关(P均>0.05)。CD68在TC PD-L2阴性组中的表达高于TC PD-L2阳性组(P<0.0001)。CD163在TC PD-L2阳性组中的表达高于TC PD-L2阴性组(P=0.0011)。CD68、CD163在TIIC PD-L2阴性组与阳性组中的表达差异均无统计学意义(P均>0.05)。Kaplan-Meier生存分析显示:TC PD-L2阳性患者的总生存期(overall survival,OS)和无进展生存期(progression-free survival,PFS)比阴性患者低(P均<0.05),TIIC PD-L2表达与OS、PFS均无关(P均>0.05)。Cox单因素和多因素分析显示:TC PD-L2阳性是影响OS和PFS的相关因素,但不是独立的预后因素。TC PD-L2阳性、CD68弱阳性以及TC PD-L2阳性、CD163强阳性患者的预后更差(P均<0.05)。结论联合检测PD-L2、CD68以及CD163表达可为HGSOC患者的预后判断提供依据,同时为免疫治疗提供实验数据。

Purpose To investigate the expression and clinical significance of PD-L2 in high-grade serous ovarian carcinoma(HGSOC).Methods Clinical data were collected from patients with HGSOC.The expression status of PD-L2,CD68,and CD163 were detected by immunohistochemistry using EnVision method,and the relationships between the expression and clinicopathological characteristics and prognosis were also investigated.Results The positive rates of tumor cell(TC)and tumor-infiltrating immune cell(TIIC)PD-L2 in HGSOC were 27.9%(17/61)and 60.7%(37/61),respectively.TC PD-L2 expression was associated with first-line platinum-containing chemotherapy,and its positive rate in platinum-resistant patients(58.3%,7/12)was higher than that in platinum-sensitive patients(20.4%,10/49)(P=0.026).However,TC PD-L2 expression was not related to age,preoperative serum CA125 level,tumor diameter,tumor distribution,surgical pathological stage,surgical satisfaction and ascites(all P>0.05).TIIC PD-L2 was not related to age,preoperative serum CA125 level,tumor diameter,tumor distribution,surgical pathological stage,surgical satisfaction,ascites and first-line platinum-containing chemotherapy(all P>0.05).CD68 expression was higher in TC PD-L2-negative group than in TC PD-L2-positive group in HGSOC(P<0.0001).CD163 expression was higher in TC PD-L2-positive group than in TC PD-L2-negative group in HGSOC(P=0.0011).However,there was no significant difference in the expressions of CD68 and CD163 between the TIIC PD-L2 negative group and the positive group(all P>0.05).Kaplan-Meier analysis showed that the TC PD-L2-positive group had shortened overall survival(OS)and progression-free survival(PFS)than the TC PD-L2-negative group in HGSOC(both P<0.05).However,the expression status of TIIC PD-L2 was not associated with the OS and PFS(both P>0.05).Univariate and multivariate regression analysis showed that TC PD-L2 was a factor affecting OS and PFS,but not an independent prognostic factor.The group with positive TC PD-L2 expression and week CD68 expression or strong CD163 expression had more unfavourable outcomes compared with the other groups(both P<0.05).Conclusion Combined detection of PD-L2,CD68 and CD163 expression may provide the basis for the prognosis prediction and provide experimental data for immunotherapy in HGSOC.