血浆sHLA-G在宫颈癌和癌前病变检测中的应用

The application of plasma soluble human leukocyte antigen in diagnosis of patients with cervical cancer and its precancerous lesion

目的 探讨血浆sHLA-G在诊断CIN及宫颈癌中的应用价值.方法 采用ELISA检测102例宫颈癌患者、72例CIN患者和20名健康对照者血浆sHLA-G水平,并分析其对宫颈癌的诊断价值及与宫颈癌临床病理参数间的关系.其中,宫颈癌患者经FIGO分期分为：Ⅰ期32例、Ⅱ期28例、Ⅲ期25例、Ⅳ期17例;按肿瘤大小分为：＜4 cm 63例、≥4 cm 39例;按病理组织类型分为：鳞癌78例、腺癌24例;高分化57例、中分化29例、低分化16例;无淋巴结转移64例、淋巴结转移38例.CIN患者中Ⅰ级21例、Ⅱ级25例、Ⅲ级26例.结果 血浆sHLA-G在宫颈癌组为193.6（151.3～287.4）kU/L,CIN Ⅰ级组为48.3（34.6～57.2）kU/L、CIN Ⅱ级组为91.3（68.2～118.6）kU/L、CIN Ⅲ级组为106.4（73.8～165.7）kU/L、健康对照组为45.2（38.0～55.5）kU/L;各组间血浆sHLA-G水平差异有统计学意义（H=13.287,P＜0.01）,且宫颈癌组明显高于CIN Ⅰ级组、CIN Ⅱ级组、CIN Ⅲ级组及健康对照组（U值分别为8.832、6.456、4.017、9.873,P均＜0.05）;CIN Ⅱ级组和CIN Ⅲ级组血浆sHLA-G水平明显高于CIN Ⅰ级组和健康对照组（U值分别为4.361、4.892、5.139、5.485,P均＜0.05）.SCC-Ag在健康对照组、CIN Ⅰ级组、CIN Ⅱ级组、CIN Ⅲ级组和宫颈癌组的水平分别为0.43（0.38～0.69）μg/L、0.47（0.35～0.72）μg/L、0.65（0.53～0.81）μg/L、0.82（0.54～1.03）μg/L和1.02（0.62～1.87）μg/L.宫颈癌组血浆SCC-Ag水平明显高于CIN Ⅰ级组、CIN Ⅱ级组及健康对照组（U值分别为7.926、4.877、8.132,P均＜0.05）;CIN Ⅲ级组血浆SCC-Ag水平明显高于CIN Ⅰ级组和健康对照组（U值分别为6.574、6.763,P均＜0.05）.CA125在健康对照组、CIN Ⅰ级组、CIN Ⅱ级组、CIN Ⅲ级组和宫颈癌组的水平分别为14.38（6.14～21.82）kU/L、15.42（6.25～23.53）kU/L、21.34（9.82～32.58）kU/L、25.69（14.47～38.71）kU/L和27.72（14.29～43.87）kU/L.宫颈癌组血浆CA125水平明显高于CIN Ⅰ级组、CIN Ⅱ级组及健康对照组（U值分别为7.564、4.522、7.429,P均＜0.05）;CIN Ⅲ级组血浆CA125水平明显高于CIN Ⅰ级组和健康对照组（U值分别为5.871、5.435,P均＜0.05）.ROC曲线分析sHLA-G的AUC为0.828（95% CI：0.768～0.879）,其诊断价值高于SCC-Ag[0.727（95% CI：0.658～0.788）;Z=2.294,P＜0.05]和CA125[0.705（95%CI：0.636～0.769）;Z=2.842,P＜0.05];SCC-Ag与CA125的诊断效能比较,差异无统计学意义（Z=0.672,P＞0.05）.经ROC曲线分析确定sHLA-G诊断临界值为109.6 kU/L时,其敏感度为86.3%,特异度为76.1%,阳性预测值为80.0%,阴性预测值为83.3%,准确性为78.4%.宫颈癌患者血浆sHLA-G水平与FIGO分期及淋巴结转移密切相关（U值分别为6.085、4.451,P均＜0.05）,而与患者年龄、肿瘤大小、组织形态及细胞分化无关（U值分别为1.274、1.956、1.268、2.719,P均＞0.05）.结论 血浆sHLA-G水平检测有助于宫颈癌及癌前病变的早期发现,并且可以作为宫颈癌病情进展及淋巴结转移的判断指标.

Objective To explore the application value of plasma sHLA-G in diagnosis of CIN and cervical cancer. Methods The plasma sHLA-G levels were detected by ELISA in 102 cases with cervical cancer（ FIGO Ⅰ stage 32 cases, Ⅱ stage 28 cases, Ⅲ stage 25 cases and Ⅳstage 17 cases; tumor size：＜4 cm 63 cases and ≥4 cm 39 cases; squamous cell carcinoma 78 cases and adenocarcinoma 24 cases;cell differentiation：well 57 cases, moderate 29 cases and poor 16 cases; lymph nodes metastasis negative64 cases and positive 38 cases ）, 72 cases with CIN（ Ⅰ grade 21 cases, Ⅱ grade 25 cases and Ⅲ grade26 cases ） and 20 cases of healthy controls. The diagnostic value of sHLA-G and its correlations with clinical parameters were analyzed. Results The plasma levels of sHLA-G were 193.6（ 151.3-287.4 ） kU/L in cervical cancer group, 48.3（ 34.6-57.2 ） kU/L in CIN Ⅰ group, 91.3（ 68.2-118.6 ） kU/L in CIN Ⅱ group, 106.4（ 73.8-165.7 ） kU/L in CIN Ⅲ group and 45.2（ 38.0-55.5 ） kU/L in health control group.The level of sHLA-G was significantly higher in cervical cancer group than that in CIN Ⅰ group, CIN Ⅱ group, CIN Ⅲ group and healthy control group（ U value of 8.832, 6.456, 4.017, 9.873, P ＜ 0.05,respectively ）. The level of sHLA-G was significantly higher in CIN Ⅱ group and CIN Ⅲ group than that in CIN Ⅰ group and health control group（ U value of 4.361,4.892, 5.139, 5.485, P ＜0.05, respectively ）.The levels of SCC Ag in healthy control group, CIN Ⅰ group, CIN Ⅱ group, CIN Ⅲ group and cervical cancer group were 0.43（ 0.38-0.69 ）μg/L, 0.47（ 0.35-0.72 ）μg/L, 0.65（ 0.53-0.81 ）μg/L, 0.82（ 0.54-1.03 ）μg/L and 1.02（ 0.62-1.87 ）μg/L. The level of SCC-Ag was significantly higher in cervical cancer group than that in CIN Ⅰ group, CIN Ⅱ group and healthy control group（ U value of 7.926, 4.877, 8.132,P ＜0.05, respectively ）. The level of SCC-Ag was significantly higher in CIN Ⅲ group than that in CIN Ⅰ group and health control group（ U value of 6.574, 6.763, P ＜0.05, respectively ）. The levels of CA125 in healthy control group, CIN Ⅰ group, CIN Ⅱ group, CIN Ⅲ group and cervical cancer group were 14.38 （ 6.14-21.82 ） kU/L, 15.42（ 6.25-23.53 ） kU/L, 21.34（ 9.82-32.58 ） kU/L, 25.69（ 14.47-38.71 ）kU/L and 27.72（ 14.29-43.87 ） kU/L. The level of CA125 was significantly higher in cervical cancer group than that in CIN Ⅰ group, CIN Ⅱ group and healthy control group（ U value of 7.564, 4.522, 7.429, P ＜0.05, respectively ）. The level of CA125 was significantly higher in CIN Ⅲ group than that in CIN Ⅰ group and health control group（ U value of 5.871, 5.435, P ＜0.05, respectively ）. ROC curve analysis showed AUC for sHLA-G was 0.828（ 95% CI：0.768-0.879 ）, which was high as compared with the AUC of SCC-Ag [ 0.727（ 95% CI：0.658-0.788 ）;Z = 2.294, P ＜ 0.05 ] and the AUC of CA125 [ 0.705（ 95% CI：0.636-0.769 ）;Z =2.842 ,P ＜0.05 ]. There was no significant difference of diagnostic efficiency between SCC and CA125（ Z =0.672, P ＞ 0.05 ）. When cutoff value of sHLA-G was 109.6 kU/L, the diagnostic sensitivity,specificity, positive predictive value, negative predictive value and accuracy rate were 86.3%, 76.1%,80.0%, 83.3%, and 78.4%, respectively. The levels of sHLA-G in cervical cancer patients were significantly correlated with FIGO stages and lymphoid node metastasis （ U value of 6.085, 4.451, P ＜0.05, respectively ）, while there were no significant differences between the levels of sHLA-G and age,tumor size, histological type and cell differentiation（ U value of 1.274, 1.956, 1.268, 2.719, P ＞0.05,respectively ）. Conclusions sHLA-G can be used for the early screening of cervical cancer and its precancerous lesion. It could also be used as an index for judging progression and lymphoid node metastasis.