血管内皮生长因子-C及其受体表达与宫颈癌生长及淋巴结转移的相关性

doi:10.3760/cma.j.issn.1673-422X.2016.08.007

摘要/Abstract

摘要： 目的探讨宫颈癌组织中血管内皮生长因子-C（VEGF-C）及血管内皮生长因子受体-2（KDR）表达与宫颈癌形成及淋巴结转移的关系。方法选取2010年1月至2013年12月于陕西省宝鸡市妇幼保健院妇科手术切除标本的72例宫颈癌组织及其癌旁组织和36例正常宫颈组织，应用半定量PCR和酶联免疫吸附试验检测VEGF-C及KDR表达情况，并分析这两种蛋白表达与宫颈癌生长及淋巴结转移的关系。结果 72例宫颈癌组织与癌旁组织中VEGF-C的mRNA表达水平分别为4.67±1.05和2.02±0.65，明显高于正常组织的0.36±0.06，差异有统计学意义（t=2.247，P=0.025；t=1.379，P=0.027）；VEGF-C蛋白表达水平分别为68.30±17.10和48.20±12.70，明显高于正常组织的18.40±10.70，差异有统计学意义（t=4.357，P=0.016；t=6.337，P=0.012）。宫颈癌组织与癌旁组织中的KDR的mRNA表达水平分别为3.52±0.95和1.92±0.87，明显高于正常宫颈组织的0.72±0.36，差异有统计学意义（t=3.127，P=0.023；t=1.214，P=0.028）。KDR的蛋白表达水平分别为47.20±15.60和38.60±11.30，明显高于正常宫颈组织的16.40±9.40，差异有统计学意义（t=3.667，P=0.020；t=0.986，P=0.032）。72例宫颈癌组织中VEGF-C蛋白表达量与年龄（χ²=0.54，P=0.17）、组织类型（χ²=0.34，P=0.25）、浸润深度（χ²=5.39，P=0.08）、病理分级（χ²=0.78，P=0.11）无关；而与肿瘤大小（χ²=22.34，P=0.02）、临床分期（χ²=32.14，P=0.01）及有无淋巴结转移（χ²=15.58，P=0.03）有关。KDR蛋白表达量与肿瘤大小（χ²=13.78，P=0.04）、组织类型（χ²=32.74，P=0.01）、病理分级（χ²=13.72，P=0.04）、浸润深度（χ²=10.27，P=0.04）、临床分期（χ²=20.25，P=0.02）以及有无淋巴结转移（χ²=19.52，P=0.02）有关，而与年龄（χ²=4.17，P=0.09）无关。结论 VEGFC及KDR表达与宫颈癌的生长、浸润和转移相关，是反映患者淋巴转移的良好指标。

关键词: 宫颈肿瘤, 淋巴转移, 血管内皮生长因子C

Abstract: Objective To study the relationship between the expressions of vascular endothelial growth factor-C (VEGF-C) and vascular endothelial growth factor receptor-2 (KDR) in cervical carcinoma and the formation of cervical cancer and lymph node metastasis. Methods We selected 72 cervical carcinoma tissues, their corresponding adjacent tissues and 36 normal cervical tissues which have been resected in the Maternal and Child Health Care Hospital of Baoji of Shaanxi Province from January 2010 to December 2013. The mRNA and protein expressions of VEGF-C and KDR were examined by semi-quantitative PCR and enzyme linked immunosorbent assay in these tissues. The relationships between the expressions of VEGF-C and KDR and the formation of cervical cancer and lymph node metastasis were analyzed. Results The mRNA levels of VEGF-C in 72 cases of cervical cancer tissues and its corresponding adjacent tissues were 4.67±1.05 and 2.02±0.65, which were significantly higher than those in normal cervical tissues (0.36±0.06), with significant differences (t=2.247, P=0.025; t=1.379, P=0.027). The protein levels of VEGF-C in 72 cases of cervical cancer tissues and their corresponding adjacent tissues were 68.30±17.10 and 48.20±12.70, which were significantly higher than those in normal cervical tissues (18.40±10.70), with significant differences (t=4.357, P=0.016; t=6.337, P=0.012). The mRNA levels of KDR in 72 cases of cervical cancer tissues and their corresponding adjacent tissues were 3.52±0.95 and 1.92±0.87, which were significantly higher than those in normal cervical tissues (0.72±0.36), with significant differences (t=3.127, P=0.023; t=1.214, P=0.028). The protein levels of KDR in 72 cases of cervical cancer tissues and their corresponding adjacent tissues were 47.20±15.60 and 38.60±11.30, which were significantly higher than those in normal cervical tissues (16.40±9.40), with significant differences (t=3.667, P=0.020; t=0.986, P=0.032). The expression level of VEGFC protein in 72 cases of cervical cancer tissues was not correlated with age (χ2=0.54, P=0.17), tissue type (χ2=0.34, P=0.25), depth of invasion (χ2=5.39, P=0.08), pathological grade (χ2=0.78, P=0.11), but was correlated with tumor size (χ2=22.34, P=0.02), clinical stage (χ2=32.14, P=0.01) and lymph node metastasis (χ2=15.58, P=0.03). The expression level of its receptor KDR was correlated with tumor size (χ2=13.78, P=0.04), tissue type (χ2=32.74, P=0.01), pathological grade (χ2=13.72, P=0.04), depth of invasion (χ2=10.27, P=0.04), clinical staging (χ2=20.25, P=0.02) and lymph node metastasis (χ2=19.52, P=0.02), but was not correlated with age (χ2=4.17, P=0.09). Conclusion The expression levels of VEGFC and KDR are correlated with the growth, invasion and metastasis of cervical cancer, which are good indicators of the lymph node metastasis.

Key words: Uterine cervical neoplasms, Lymphatic metastasis, Vascular endothelial growth factor C

燕海亚, 王婕. 血管内皮生长因子-C及其受体表达与宫颈癌生长及淋巴结转移的相关性 [J]. 国际肿瘤学杂志, 2016, 43(8): 588-592.

Yan Haiya, Wang Jie. The relationship among the expressions of vascular endothelial growth factor-C and its receptor and the cervical cancer growth and lymph node metastasis[J]. Journal of International Oncology, 2016, 43(8): 588-592.

参考文献

［1］纪常生. 早期宫颈癌微淋巴转移病理与临床的关系［J］. 中国实用医药, 2015, 10(2): 76-77. DOI: 10.14163/j.cnki.11-5547/r.2015.02.048. ［2］ Burzawa J, Gonzales N, Frumovitz M. Challenges in the diagnosis and management of cervical neuroendocrine carcinoma［J］. Expert Rev Anticancer Ther, 2015, 15(7): 805-810. DOI: 10.1586/14737140.2015.1047767. ［3］李淼, 闫风彩, 钱智, 等. 宫颈癌组织中Survivin、Ki-67及VEGF的表达及相关性［J］. 现代肿瘤医学, 2011, 19(7): 1396-1399. DOI: 10.3969/j.issn.1672-4992.2011.07.47. ［4］ Zhu P, Zhang J, Chen Q, et al. Expression of vascular endothelial growth factor-C in gastric carcinoma and the effect of its antisense gene transfection on the proliferation of human gastric cancer cell line SGC-7901［J］. Am J Surg, 2012, 204(1): 78-83. DOI: 10.1016/j.amjsurg.2011.06.056. ［5］ Wang TB, Wang J, Wei XQ, et al. Serum vascular endothelial growth factor-C combined with multi-detector CT in the preoperative diagnosis of lymph node metastasis of gastric cancer ［J］. Asia Pac J Clin Oncol, 2012, 8(2): 180-186. DOI: 10.1111/j.1743-7563.2011.01490.x. ［6］ Yu H, Zhang S, Zhang R, et al. The role of VEGF-C/D and Flt4 in the lymphatic metastasis of early-stage invasive cervical carcinoma［J］. J Exp Clin Cancer Res, 2009, 28: 98. DOI: 10.1186/1756-9966-28-98. ［7］侯亚超, 邓靖宇, 梁寒. VEGF-C/D及其受体与胃癌淋巴转移关系的研究进展［J］. 中国肿瘤临床, 2014, 41(24): 1608-1611. DOI: 10.3969/j.issn.1000-8179.20140407. ［8］沈飞琼, 魏素菊. VEGF-C及其受体VEGFR-2/3与肺癌关系的研究进展［J］. 实用癌症杂志, 2013, 28(4): 452-455. DOI: 10.3969/j.issn.1001-5930.2013.04.043. ［9］周晓琳. 肝癌组织中VEGF-C及其受体Fit-4的表达及意义［J］. 临床与实验病理学杂志, 2013, 29(3): 340-342. ［10］ Shibuya M. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling in angiogenesis: a crucial target for anti-and pro-angiogenic therapies［J］. Genes Cancer, 2011, 2(12): 1097-1105. DOI: 10.1177/1947601911423031. ［11］Klasa-Mazurkiewicz D, Jarzab M, Milczek T, et al. Clinical significance of VEGFR-2 and VEGFR-3 expression in ovarian cancer patients［J］. Pol J Pathol, 2011, 62(1): 31-40. ［12］Chen Y, Jiang L, She F, et al. Vascular endothelial growth factor-C promotes the growth and invasion of gallbladder cancer via an autocrine mechanism［J］. Mol Cell Biochem, 2010, 345(1-2): 77-89. DOI: 10.1007/s11010-010-0562-y. ［13］Chen H, Suo K, Cheng Y, et al. Vascular endothelial growth factor C enhances cervical cancer migration and invasion via activation of focal adhesion kinase［J］. Gynecol Endocrinol, 2013, 29(1): 20-24. DOI: 10.3109/09513590.2012.705387. ［14］Fujiwaki R, Hata K, Iida K, et al. Vascular endothelial growth factor expression in progression of cervical cancer: correlation with thymidine phosphorylase expression, angiogenesis, tumor cell proliferation, and apoptosis［J］. Anticancer Res, 2000, 20(2B): 1317-1322. ［15］孟琴, 纪新强. RKIP和VEGF在宫颈癌及癌前病变中表达的临床研究［J］. 山东医学高等专科学校学报, 2011, 33(2): 8790. DOI: 10.3969/j.issn.1674-0947.2011.02.004. ［16］Tampouris AI, Kandiloros D, Giotakis I, et al. The role of the VEGF-C/-D/flt-4 autocrine loop in the pathogenesis of salivary neoplasms［J］. Pathol Res Pract, 2012, 208(3): 151-156. DOI: 10.1016/j.prp.2011.12.013. ［17］Yu H, Zhang S, Zhang R, et al. The role of VEGF-C/D and Flt4 in the lymphatic metastasis of early-stage invasive cervical carcinoma［J］. J ExpClin Cancer Res, 2009, 28: 98. DOI: 10.1186/1756-9966-28-98.

[1]	张宁宁, 杨哲, 檀丽梅, 李振宁, 王迪, 魏永志. 宫颈细胞DNA倍体分析联合B7-H4和PKCδ对宫颈癌的诊断价值[J]. 国际肿瘤学杂志, 2024, 51(5): 286-291.
[2]	张露, 蒋华, 林州, 马辰莺, 徐晓婷, 王利利, 周菊英. 免疫检查点抑制剂治疗复发转移性宫颈癌的疗效及预后分析[J]. 国际肿瘤学杂志, 2023, 50(8): 475-483.
[3]	吕璐, 孙鹏飞. 肠道菌群与宫颈癌[J]. 国际肿瘤学杂志, 2023, 50(6): 373-376.
[4]	曾利武, 杜雨强, 张鹏, 陶凯雄. 直肠癌侧方淋巴结转移的影像评估进展[J]. 国际肿瘤学杂志, 2023, 50(4): 248-251.
[5]	段传菊, 陈真云, 李晓红, 牛洪朋, 李秀敏. 复发宫颈癌免疫治疗1例[J]. 国际肿瘤学杂志, 2023, 50(12): 766-768.
[6]	马雪艳, 鲁历历, 孙鹏飞. 免疫微环境在宫颈癌中的研究进展[J]. 国际肿瘤学杂志, 2023, 50(1): 47-50.
[7]	张露, 周菊英, 马辰莺, 林州. 复发转移性宫颈癌免疫治疗相关进展[J]. 国际肿瘤学杂志, 2022, 49(9): 517-520.
[8]	史英侠, 胡莉钧, 于静萍. 免疫检查点抑制剂在复发或转移性宫颈癌治疗中的应用[J]. 国际肿瘤学杂志, 2022, 49(9): 568-571.
[9]	彭琛, 谢印通, 张昕, 谢鹏. 宫颈癌维持治疗研究进展[J]. 国际肿瘤学杂志, 2022, 49(7): 430-435.
[10]	熊婵, 阎英, 谢晓冬, 孟繁杰, 于卉影. 辐射诱导的多倍体宫颈癌HeLa细胞生物学特性研究[J]. 国际肿瘤学杂志, 2022, 49(5): 263-269.
[11]	袁晨阳, 周菊英. 宫颈癌预后因素的研究进展[J]. 国际肿瘤学杂志, 2022, 49(5): 307-313.
[12]	袁晨阳, 周菊英, 杜霄, 纪环, 赵天翼. 宫颈癌2018与2009 FIGO分期的比较及预后因素分析[J]. 国际肿瘤学杂志, 2022, 49(3): 151-163.
[13]	王玥, 吴琼, 许愿, 龚唯, 徐晓婷. 老年宫颈癌的筛查与治疗进展[J]. 国际肿瘤学杂志, 2022, 49(12): 754-758.
[14]	李劲浩, 王桂东, 李雪菲, 刘子琳, 孟凯龙. 静脉期CT值预测甲状腺乳头状癌中央组淋巴结转移的临床研究[J]. 国际肿瘤学杂志, 2022, 49(10): 581-585.
[15]	马秀珍, 卢艳, 赵冰冰, 邱宏聪, 徐勋, 韦敏. 岗松总黄酮对宫颈癌SiHa细胞迁移、侵袭及凋亡的影响[J]. 国际肿瘤学杂志, 2021, 48(4): 206-211.