Expression of HPV16E6 and Indoleamine 2, 3-dioxygenase in Cervical Lesions and Its Clinical Implications
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摘要:
目的 检测高危HPV感染的正常宫颈组织、宫颈癌前病变组织、宫颈癌组织HPV16E6和IDO的表达，分析二者在宫颈病变组织恶化过程中的关系，探讨其作为宫颈癌肿瘤标志物的可能性。 方法 把经第二代杂交捕获（HC-2）法行HPV DNA检测为高危型HPV感染的宫颈病变者120例为实验对象，正常宫颈组织、宫颈癌前病变组织、宫颈癌组织各40例。免疫组化染色法检测各组织中HPV16E6和IDO的表达情况。 结果 40例正常宫颈组织中HPV16E6和IDO阳性表达率分别为7.5%、0%；40例宫颈癌前病变组织中HPV16E6和IDO阳性表达率分别为37.5%、22.5%。40例宫颈癌组织中HPV16E6和IDO阳性表达率分别为90%、80%。在宫颈病变组织恶化过程中HPV16E6和IDO的阳性表达呈正相关（rs = 0.710，P = 0.000）。 结论 HPV16E6和IDO的表达随宫颈病变的进展而呈现出阳性程度逐渐递增趋势，HPV16E6和IDO可考虑成为预测宫颈病变组织恶化的肿瘤标志物。 -
关键词:
- 人乳头瘤病毒 /
- 宫颈病变组织 /
- HPV16E6 /
- 吲哚胺2，3-二氧化酶
Abstract:Objective To explore the potential of HPV16E6 and IDO as a tumor markers of cervical cancer, the expression of high-risk HPV-infected normal cervical tissue, cervical precancerous lesions, cervical cancer tissue HPV16E6 and IDO, the correlation between HPV16E6 and IDO in the progression of cervical lesions were analyzed. Methods 120 cases of cervical lesions with high-risk HPV infection detected by HPV DNA in the second generation hybrid capture（HC-2）method were used as experimental subjects, 40 cases each in normal cervical tissue group, cervical precancerous lesions group and cervical cancer tissues group, respectively. The expression of HPV16E6 and IDO in each tissue group was detected by immunohistochemical staining. Results The expression rates of HPV16E6 and IDO in 40 cases of normal cervical tissues were 7.5% and 0%, respectively. The expression rates of HPV16E6 and IDO in 40 cases of cervical precancerous lesions were 37.5% and 22.5%, respectively. The positive expression rates of HPV16E6 and IDO in 40 cases of cervical cancer tissues were 90% and 80%, respectively. The positive expression of HPV16E6 and IDO was positively correlated in the progression of cervical lesions（rs = 0.710, P = 0.000）. Conclusion The expression of HPV16E6 and IDO showed a positive trend with the progress of cervical lesions. HPV16E6 and IDO have the potential of tumor markers for predicting the progression cervical lesions. -
Key words:
- HPV /
- Cervical lesion tissue /
- HPV16E6 /
- IDO
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表 1 不同组别中HPV16E6蛋白表达阳性率比较[n（%）]
Table 1. Comparison of HPV16E6 expression rates in different groups [n（%）]
组别 n − + ++ +++ 阳性表达 P 正常组 40 37（92.5） 3（7.5） 0（0） 0（0） 3（7.5） CINⅠ-Ⅱ 25 17（68） 4（16） 4（16） 0（0） 8（32）* 0.010 CINⅢ 15 8（53.3） 2（13.3） 4（26.7） 1（6.7） 7（46.7）** 0.001 宫颈癌ⅠA-ⅡA 28 4（14.3） 3（10.7） 15（53.6） 6（21.4） 24（85.7）** 0.000 宫颈癌≥ⅡB 12 0（0） 2（16.7） 3（25） 7（58.3） 12（100）** 0.000 与正常组比较，*P < 0.05；** P < 0.01。 
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表 2 40例宫颈癌组织中HPV16E6蛋白表达水平与宫颈癌临床病理因素的关系（n）
Table 2. Relationship between HPV16E6 protein expression and clinical pathological factors in cervical cancer in 40 cases of cervical cancer（n）
临床病理因素 n 阳性 阴性 阳性表达率（%） P 年龄（岁） ≤53 11 10 1 90.9 0.906 > 53 29 26 3 89.7 病理类型 鳞癌 32 29 3 90.6 0.792 非鳞癌 8 7 1 87.5 肿瘤大小 ≤4 cm 31 27 4 87.1 0.256 > 4 cm 9 9 0 100.0 临床分期 Ⅰ-ⅡA 28 24 4 85.7 0.168 ≥ⅡB 12 12 0 100 深肌层浸润 有 26 26 0 100.0* 0.004 无 14 10 4 71.4 盆腔淋巴结转移 有 13 13 0 92.3 0.144 无 27 23 4 85.2 *P < 0.05。
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表 3 不同组别中IDO阳性率比较（n（%））
Table 3. Comparison of IDO expression rates in different groups [n（%）]
组别 n − + ++ +++ 阳性表达 P 正常组 40 40（100） 0（0） 0（0） 0（0） 0（0） CINⅠ-Ⅱ 25 22（88） 2（8） 1（4） 0（0） 3（12）* 0.025 CINⅢ 15 9（60） 3（20） 3（20） 0（0） 6（40）** 0.000 宫颈癌ⅠA-ⅡA 28 7（25） 5（18） 11（39） 5（18） 21（75）** 0.000 宫颈癌≥ⅡB 12 0（0） 1（8） 3（25） 8（67） 11（100）** 0.000 与正常组比较，*P < 0.05；** P < 0.01。
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表 4 HPV16E6、IDO在各研究对象中表达的相关性
Table 4. Correlation of HPV16E6 and IDO expression in each group
HPV16E6 IDO 合计 − + ++ +++ − 62 2 1 1 66 + 7 4 2 1 14 ++ 6 4 13 1 24 +++ 3 1 2 10 16 合计 78 11 18 13 120
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[1] 李丽娜. 宫颈癌发生和病理进程的不同阶段与IDO表达的相关性[J].中国实验诊断学,2015,19(10):1742-1744. [2] 廖琪. IDO在不同宫颈病变组织中的表达及意义[J].中国伤残医学,2013,21(10):283-284. [3] Mirabello L,Clarke M A,Nelson C W,et al. The Intersection of HPV epidemiology,Genomics and mechanistic studies of HPV-mediated carcinogenesis[J]. Viruses,2018,10(2):80. doi: 10.3390/v10020080 [4] Tortora M,Annunziata C,Liguori G,et al. Detection of human papillomavirus DNA in peri-tumor tissues and pelvic lymph nodes as potential molecular marker of micrometastasis in cervical cancer[J]. Infect Agent Cancer,2016,11(1):1-7. doi: 10.1186/s13027-016-0047-z [5] Shuling Liu,Takeo Minaguchi,Bouchra Lachkar,et al. Separate analysis of human papillomavirus E6 and E7 messenger RNAs to predict cervical neoplasia progression[J]. PLoS One,2018,13(2):e0193061. doi: 10.1371/journal.pone.0193061 [6] Wen-Jing Shi,Hao Liu,Dan Wu,et al. E6/E7 proteins are potential markers for the screening and diagnosis of cervical pre-cancerous lesions and cervical cancer in a Chinese population[J]. Oncol Lett,2017,14(5):6251-6258. [7] Ye-li Yao,Qi-fang Tian,Bei Cheng,et al. Human papillomavirus(HPV)E6/E7 mRNA detection in cervical exfoliated cells:A potential triage for HPV-positive women[J]. J Zhejiang Univ Sci B,2017,18(3):256-262. doi: 10.1631/jzus.B1600288 [8] Nerea Fontecha,Miren Basaras,Silvia Hernáez,et al. Assessment of human papillomavirus E6/E7 oncogene expression as cervical disease biomarker[J]. BMC Cancer,2016,16(1):852. doi: 10.1186/s12885-016-2885-x [9] Roberta Zappacosta,Francesca Sablone,Lucia Pansa,et al. Analytic and diagnostic performances of human papillomavirus E6/E7mRNA test on up-to 11-year-old liquid-based cervical samples. A biobank-based longitudinal study[J]. Int J Mol Sci,2017,18(7):1480. doi: 10.3390/ijms18071480 [10] Maria Teresa Bruno,Martina Ferrara,Valentina Fava,et al. HPV genotype determination and E6/E7 mRNA detection for management of HPV positive women[J]. Virol J,2018,15(1):52. doi: 10.1186/s12985-018-0957-z [11] Mabuchi R,Hara T,Matsumoto T,et al. High serum concentration of L-kynurenine predicts unfavorable outcomes in patients with acute myeloid leukemia[J]. Leuk Lymphoma,2016,57(1):92-98. doi: 10.3109/10428194.2015.1041388 [12] Shibata Y,Hara T,Nagano J,et al. The Role of Indoleamine 2,3-dioxygenase in diethylnitrosamine-induced liver carcinogenesis[J]. PLo S One,2016,11(1):e014627. [13] Ferns D M, Kema I P, Buist M R, et al. Indoleamine-2, 3-dioxygenase（IDO）metabolic activity is detrimental for cervical cancer patient survival[J]. 2015, 4（2）: e981457. [14] Meng X,Du G,Ye L Ogawa M,et al. Expression of CXCR-4 and IDO in human colorectal cancer:An immunohistochemical approach[J]. Mol Clin Oncol,2017,6(5):701-704. doi: 10.3892/mco.2017.1207 [15] Asghar K,Farooq A,Zulfiqar B,et al. Indoleamine 2,3-dioxygenase:As a potential prognostic marker and immunotherapeutic target for hepatocellular carcinoma[J]. World J Gastroenterol,2017,23(13):2286-2293. doi: 10.3748/wjg.v23.i13.2286 [16] Meng X,Du G,Ye L,et al. Combinatorial antitumor effects of indoleamine 2,3-dioxygenase inhibitor NLG919 and paclitaxel in a murine B16-F10 melanoma model[J]. Int J Immunopathol Pharmacol,2017,30(3):215-226. doi: 10.1177/0394632017714696 -
