血清细胞因子检测在卵巢上皮性肿瘤进展评估中的价值

Roles of serum cytokine determinations in progression of epithelial ovarian cancer

目的 探讨卵巢上皮性肿瘤患者血清12种细胞因子[白细胞介素(IL)-1β、IL-2、IL-4、IL-5、IL-6、IL-8、IL-10、IL-12、IL-17、γ-干扰素(INF-γ)、α-干扰素(IFN-α)、肿瘤坏死因子-α(TNF-α)]检测的临床价值。方法 选取2021年5月—2023年5月复旦大学附属肿瘤医院卵巢上皮性肿瘤患者67例(卵巢癌组)、卵巢良性肿物(卵巢囊肿、囊腺瘤等)患者22例(卵巢良性病变组)、健康体检者21名(正常对照组)。收集所有研究对象的临床资料,检测血清12种细胞因子水平。对所有患者进行术后随访,随访截止日期为2023年9月1日。采用Kaplan-Meier生存曲线评估所有患者的生存情况。结果 卵巢癌组血清IL-5、IL-8、IL-10、IL-17、TNF-α和IFN-γ水平均显著低于正常对照组(P<0.05),卵巢癌组TNF-α水平显著低于卵巢良性病变组(P<0.05),其他细胞因子3组之间差异均无统计学意义(P>0.05)。卵巢癌组IL-6阳性率最高(85.1%),其次为IL-10(49.3%)和IL-8(40.3%),其他细胞因子阳性率均<40.0%。在糖类抗原(CA)125和人附睾蛋白4(HE4)阳性的卵巢上皮性肿瘤患者中,IL-4、TNF-α和IFN-γ阴性率显著高于阳性率(P<0.05)。国际妇产科联合会(FIGO)分期为进展期、组织学类型为浆液性、有腹水和有淋巴转移的卵巢上皮性肿瘤患者血清辅助性T细胞(Th)2型细胞因子(IL-4、IL-6、IL-10)阳性率显著高于Th1型细胞因子(IL-2、TNF-α、IFN-γ)阳性率(P<0.05)。除不同FIGO分期之间Th1型细胞因子阳性率差异有统计学意义(P=0.001)外,其他不同临床病例特征的卵巢上皮性肿瘤患者之间Th1型和Th2型细胞因子阳性率差异均无统计学意义(P>0.05)。Kaplan-Meier生存曲线分析结果显示,IL-2、IL-6和IL-10阳性组无进展生存期(PFS)短于相应的阴性组(Log-rankχ^(2)值分别为3.567、4.463、3.997,P值分别为0.046、0.013、0.035),IL-17阳性组PFS长于阴性组(Log-rankχ^(2)=3.659,P=0.043),其他细胞因子阳性组与阴性组之间PFS差异均无统计学意义(P>0.05)。结论 细胞因子检测有助于监测卵巢上皮性肿瘤患者炎症状态和免疫功能,在判断疾病进展和预后评估方面有一定的价值。

Objective To investigate the clinical roles of serum 12 cytokines[interleukin(IL)-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12,IL-17,interferon-gamma(INF-γ),interferon-alpha(IFN-α),tumor necrosis factor-alpha(TNF-α)]determinations in patients with epithelial ovarian cancer.Methods From May 2021 to May 2023,67 patients with epithelial ovarian cancer(ovarian cancer group),22 patients with benign ovarian tumors(ovarian cysts,cystadenomas and so on)(benign group)and 21 healthy subjects(healthy control group)were enrolled from Shanghai Cancer Center of Fudan University.The clinical data of all the subjects were collected,and serum levels of 12 cytokines were determined.All the patients were followed up until September 1st,2023.The survival of all the patients was analyzed by Kaplan-Meier curve.Results Compared with healthy control group,serum levels of IL-5,IL-8,IL-10,IL-17,TNF-αand IFN-γwere decreased in ovarian cancer group(P<0.05),and the level of TNF-αin ovarian cancer group was lower than that in benign group(P<0.05).There was no statistical significance in the other cytokines among the 3 groups(P>0.05).The positive rate of IL-6 was the highest in ovarian cancer group(85.1%),followed by IL-10(49.3%)and IL-8(40.3%),and the positive rates of the other cytokines were<40%.The negative rates of IL-4,TNF-αand IFN-γwere higher than positive rates in patients with carbohydrate antigen(CA)125 and human epididymis protein 4(HE4)-positive epithelial ovarian cancer(P<0.05).The positive rates of serum T helper cell(Th)2 cytokines(IL-4,IL-6,IL-10)were higher than those of Th1 cytokines(IL-2,TNF-α,IFN-γ)in patients with advanced the International Federation of Gynecology and Obstetrics(FIGO)stage,serous histological type,ascites and lymphatic metastasis(P<0.05).There was statistical significance in the positive rate of Th1 cytokines among different FIGO stages(P=0.001).However,no statistical significance was found in the positive rates of Th1 and Th2 cytokines for epithelial ovarian cancer patients with different clinical characteristics(P>0.05).The progression-free survival(PFS)of the positive group of IL-2,IL-6 and IL-10 was shorter than that of the corresponding negative group(Log-rankχ^(2) values were 3.567,4.463 and 3.997,P=0.046,0.013 and 0.035,respectively).The PFS in the positive group of IL-17 was longer than that in the corresponding negative group(Log-rankχ^(2) value was 3.659,P=0.043),but there was no statistical significance in PFS between the positive group and the negative group of the other cytokines(P>0.05).Conclusions Cytokine determination is helpful to monitor inflammatory status and immune function in patients with epithelial ovarian cancer,and has a certain value in judging disease progression and evaluating prognosis.