探讨X染色体连锁凋亡抑制蛋白(XIAP)与XIAP相关因子(XAF1)异常表达与卵巢癌的相关性。

选择2018年6月至12月于四川大学华西第二医院妇科进行卵巢癌患者全面临床分期手术，经术后切除卵巢癌组织的活组织病理学检查，被诊断为卵巢癌的72例患者为研究对象，纳入卵巢癌组；进一步按照组织病理学检查结果将其分为中-高分化亚组(n＝24)与低分化亚组(n＝48)，浆液性癌亚组(n＝36)与非浆液性癌亚组(n＝36)；按照国际妇产科联盟(FIGO)临床分期进一步分为Ⅰ~Ⅱ期亚组(n＝35)与Ⅲ~Ⅳ期亚组(n＝37)，淋巴结未转移亚组(n＝59)与淋巴结转移亚组(n＝13)。选择同期在同一家医院，因卵巢畸胎瘤、卵巢囊肿等进行患侧卵巢手术，并经术后切除组织的活组织病理学检查，被诊断为良性卵巢肿瘤的35例良性卵巢肿瘤患者，以及因子宫腺肌病、子宫肌瘤等，进行全子宫及双附件切除术，并经术后切除组织的活组织病理学检查，被诊断为子宫腺肌病、子宫肌瘤的卵巢功能正常的30例患者作为对照，分别纳入良性肿瘤组与对照组。采用免疫组织化学(IHC)法检测3组患者手术切除卵巢组织的XIAP与XAF1表达情况。对3组患者手术切除卵巢组织的XIAP与XAF1阳性表达率比较，采用χ²检验。采用Spearman秩相关性分析，对卵巢癌组患者XAF1与XIAP表达水平相关性进行分析。3组患者年龄等一般临床资料比较，差异无统计学意义(P>0.05)。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求。

①卵巢癌组、良性肿瘤组及对照组患者卵巢组织的XIAP阳性表达率分别为81.3%(60/72)、51.4%(18/35)、46.7%(14/30)，XAF1阳性表达率分别为38.9%(28/72)、80.0%(28/35)、86.7%(26/30)，3组患者卵巢组织的XIAP、XAF1阳性表达率分别总体比较，差异均有统计学意义(χ²＝18.12、28.06，P<0.001)。进一步对其分别进行两两比较结果显示，卵巢癌组患者卵巢癌组织的XIAP阳性表达率，显著高于良性肿瘤组与对照组，而XAF1阳性表达率，则显著低于良性肿瘤组、对照组，并且差异均有统计学意义(P均<0.001)；而良性肿瘤组与对照组患者卵巢组织的XIAP、XAF1阳性表达率分别比较，差异均无统计学意义(P＝0.072、0.475)。②低分化亚组、Ⅰ~Ⅱ期亚组、淋巴结未转移亚组卵巢癌患者卵巢癌组织XAF1阳性表达率分别为91.7%(44/48)、51.4%(18/35)、45.8%(27/59)，分别显著高于中-高分化亚组的66.7%(16/24)、Ⅲ~Ⅳ期亚组的27.0%(10/37)、淋巴结转移亚组的7.7%(1/13)，并且差异亦均有统计学意义(χ²＝7.20、4.51、6.50，P＝0.007、0.034、0.011)。③在浆液性癌亚组与非浆液性癌亚组患者卵巢癌组织中，XIAP与XAF1阳性表达强度相关性均无统计学意义(r_s＝－0.315、0.094，P＝0.585、0.062)。

与正常卵巢组织、良性卵巢肿瘤组织相比，卵巢癌患者卵巢癌组织XAF1表达降低，而XIAP表达则增高。卵巢癌患者中，卵巢癌组织XIAP表达水平与卵巢癌组织分化程度有关，XAF1表达水平则与患者FIGO临床分期、淋巴结转移有关，二者相关性有待进一步研究、证实。

To explore the correlation of abnormal expression of X-linked inhibitor of apoptosis protein (XIAP) and XIAP associated factor (XAF)1 with ovarian cancer.

A total of 72 patients diagnosed with ovarian cancer based on postoperative histopathological examination following comprehensive staging surgery in the Department of Gynecology, West China Second University Hospital, Sichuan University from June to December 2018 were selected as subjects, and were included into ovarian cancer group. Based on results of histopathological examination, they were further divided into moderately and well-differentiated subgroup (n=24) and poorly differentiated subgroup (n=48), serous carcinoma subgroup (n=36) and non-serous carcinoma subgroup (n=36); according to the International Federation of Gynecology and Obstetrics (FIGO) clinical staging, they were further divided into stage Ⅰ-Ⅱ subgroup (n=35) and stage Ⅲ-Ⅳ subgroup (n=37), without lymph node metastasis subgroup (n=59) and lymph node metastasis subgroup (n=13). And 35 ovarian benign tumor patients who underwent unilateral ovarian cystectomy for ovarian teratoma, ovarian cyst, and so on in the same hospital during the same period and were histopathologically diagnosed with benign ovarian tumors postoperatively, were included into benign tumor group. And 30 patients who underwent total hysterectomy with bilateral salpingo-oophorectomy for adenomyosis and uterine fibroids and were histopathologically diagnosed with adenomyosis and uterine fibroids, while maintaining normal ovarian function, were included into normal control group. Immunohistochemistry (IHC) was used to detect the expression of XIAP and XAF1 in surgically excised ovarian tissues of three groups. Chi-square test were conducted for comparison of positive expression rates of XIAP and XAF1 in surgically excised ovarian tissue among three groups. Spearman′s rank correlation analysis was used to analyze the correlation between XAF1 and XIAP expression in patients of ovarian cancer group. There were no statistical differences among three groups in general clinical data, such as age and so on (P>0.05). The procedures followed in this study were in accordance with the requirements of World Medical Association Declaration of Helsinki revised in 2013.

①The positive expression rates of XIAP in ovarian tissue of ovarian cancer group, benign tumor group and normal control group were 81.3% (60/72), 51.4% (18/35), 46.7% (14/30), respectively, and XAF1 positive expression rates were 38.9% (28/72), 80.0% (28/35), 86.7% (26/30), respectively. There were statistically significant differences in overall comparison of positive expression rates of XIAP and XAF1 in ovarian tissue of three groups (χ²=18.12, 28.06; P<0.001). Further pairwise comparisons revealed that the positive expression rate of XIAP in ovarian tissue of ovarian cancer group was significantly higher than that in benign tumor group and normal control group, while the positive expression rate of XAF1 in ovarian tissue of ovarian cancer group was significantly lower than that in benign tumor group and normal control group, and all the differences were statistically significant (P all <0.001). However, there were no statistically significant differences in positive expression rates of XIAP and XAF1 in ovarian tissue of benign tumor group and normal control group (P=0.072, 0.475). ②The positive expression rates of XIAP in ovarian tissue of ovarian cancer patients in poorly differentiated subgroup, Ⅰ-Ⅱ subgroup and without lymph node metastasis subgroup were 91.7% (44/48), 51.4% (18/35) and 45.8% (27/59) respectively, which all were significantly higher than a rate of 66.7% (16/24) in moderately and well-differentiated subgroup, 27.0% (10/37) in Ⅲ-Ⅳ subgroup, and 7.7% (1/13) in lymph node metastasis subgroup (χ²=7.20, 4.51, 6.50; P=0.007, 0.034, 0.011). ③In ovarian tissue of serous carcinoma subgroup and non-serous carcinoma subgroup, there were no statistically significant differences in correlation between positive expression intensities of XIAP and XAF1 (r_s=-0.315, 0.094; P=0.585, 0.062).

Compared to normal ovarian tissue and benign ovarian tumor tissue, ovarian cancer tissue exhibits decreased expression of XAF1 and increased expression of XIAP. Among ovarian cancer patients, expression of XIAP in ovarian cancer tissue is associated with the differentiation degree of ovarian cancer tissue, while expression of XAF1 is related to FIGO clinical stage and lymph node metastasis. The correlation between XIAP and XAF1 in ovarian cancer patients needs to be confirmed by further studies.