Chinese Medical E-ournals Database

Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition) ›› 2016, Vol. 12 ›› Issue (06): 627 -632. doi: 10.3877/cma.j.issn.1673-5250.2016.06.002

Special Issue:

Original Article

Expression and correlation of human papillomavirus and C-X-C chemokine receptor 7 in cervical cancer and intraepithelial neoplasm

Pengfei Deng1, Huawen Li1,(), Weifen Wu2, Yan Zuo1, Dahong Ren3, Jianhong Huang4, Lifan Zhang1, Lihua Li1, Qifang Liu1   

  1. 1. Department of Gynecology, Zhuhai People′s Hospital, Zhuhai 519000, Guangdong Province, China
    2. Population and Family Planning Service of Baijiao Town, Doumen, Zhuhai 519125, Guangdong Province, China
    3. Department of Pathology, Zhuhai People′s Hospital, Zhuhai 519000, Guangdong Province, China
    4. Department of Clinical Laboratory, Zhuhai People′s Hospital, Zhuhai 519000, Guangdong Province, China
  • Received:2016-09-08 Revised:2016-10-30 Published:2016-12-01
  • Corresponding author: Huawen Li
  • About author:
    Corresponding author: Li Huawen, Email:
Objective

To investigate the correlation between human papillomavirus (HPV) -16, -18 and C-X-C chemokine receptor (CXCR) 7 in cervical cancer and intraepithelial neoplasm.

Methods

A total of 59 patients who underwent cervix resection and were diagnosed as cervical cancer by pathological detection, 86 patients who under went cervix resection and were diagnosed as cervical intraepithelial neoplasm (CIN) by pathological detection and 20 patients who underwent cervix resection due to other diseases were collected as study subjects in the Zhuhai People′s Hospital from March 2011 to March 2013. They were enrolled into cervical cancer group (n=59), CIN group (n=86) and control group (n=20), respectively. The expression of CXCR7 was examined by immunohistochemical, and the difference of CXCR7 expression among 3 groups were analyzed. Subsequently, the relative expression of HPV-16 DNA and HPV-18 DNA were verified with quantitative real-time PCR. Eventually, the protein expression profile of CXCR7 and stromal cell-derived factor (SDF)-1 were tested by Western blotting among 3 groups, and then the correlation analysis were performed between the expression HPV-16 DNA, HPV-18 DNA and CXCR7. There were no significant differences between two groups in age and other general clinical data (P>0.05).

Results

①The expression positive rates of CXCR7 in cervical tissues of cervical cancer group and CIN group both were significantly higher than that of control group, which were 88.1% (52/59) vs 15.0% (3/20) and 46.5% (40/86) vs 15.0% (3/20), and both the differences were statistically significant (χ2=37.77, P<0.001; χ2=6.68, P=0.010). ②The expression of HPV-16 DNA in CIN Ⅰ, CIN Ⅱ, CIN Ⅲ and cervical cancer tissues were (1.50±0.05) times, (2.87±0.09) times, (3.17±0.12) times and (6.41±0.20) times as much as that in normal cervix tissues, respectively, and the expression of HPV-16 DNA in CIN Ⅲ and cervical cancer tissues both were significantly higher than that in normal cervix tissues, and both the differences were statistically significant (t=2.15, P=0.042; t=3.11, P=0.003). Likewise, the expression of HPV-18 DNA in CIN Ⅰ, CIN Ⅱ, CIN Ⅲ and cervical cancer tissues were (1.56±0.07) times, (2.45±0.11) times, (3.89±0.16) times and (6.12±0.17) times as much as that in normal cervix tissues, respectively, and the expression of HPV-18 DNA in CIN Ⅲ and cervical cancer tissues both were significantly higher than in normal cervix tissues, and both the differences were statistically significant (t=2.21, P=0.024; t=3.03, P=0.004). ③The expression of CXCR7 and SDF-1 increased as the the deterioration of the disease by Western blotting. Not only that, there were positive correlation between CXCR7 expression and HPV-16 DNA (r=0.74, P<0.001), and HPV-18 DNA (r=0.78, P<0.001).

Conclusion

HPV may contribute the progression of cervical cancer induced by high-risk HPV.

图1 宫颈癌组、CIN组及对照组宫颈组织标本中CXCR7的免疫组织化学SP染色结果(图1A:对照组;图1B:CIN组;图1C:宫颈癌组)(SP染色,高倍)
图2 宫颈癌组、CIN组及对照组的宫颈组织标本中HPV-16、-18 DNA相对表达量比较
图3 宫颈癌组、CIN组及对照组HPV-16、-18 DNA表达量和CXCR7表达量的相关性(图3A:正常宫颈、CIN及宫颈癌组织中CXCR7和SDF-1蛋白表达量的Western blotting检测结果;图3B:HPV-16 DNA表达量与CXCR7表达量的相关性分析;图3C:HPV-18 DNA表达量与CXCR7表达量的相关性分析)
[1]
Torre LA, Bray F, Siegel RL, et al. Global cancer statistic, 2012[J]. CA Cancer J Clin, 2015, 65(2): 87-108.
[2]
Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: source, methods and major patterns in GLOBOCAN 2012[J]. Int J Cancer, 2015, 136(5): E359- E386.
[3]
Chen WQ, Zheng RS, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132.
[4]
Li Q, Bao W, Fan Q, et al. Epidermal growth factor receptor kinase substrate 8 promotes the metastasis of cervical cancer via the epithelial-mesenchymal transition[J]. Mol Med Rep, 2016, 14(4): 3220-3228.
[5]
Muller A, Homey B, Soto H, et al. Involvement of chemokine receptors in breast cancer metastasis[J]. Nature, 2001, 410(6824): 50-56.
[6]
Kryczek I, Lange A, Mottram P. CXCL12 and vascular endothelial growth factor synergistically induce neoangiogenesis in human ovarian cancers[J]. Cancer Res, 2005, 65(2): 465-472.
[7]
Kucia M, Jankowski K, Reca R, et al. CXCR4-SDF-1 signalling, locomotion, chemotaxis and adhesion[J]. J Mol Histol, 2004, 35(3): 233-245.
[8]
Kajiyama H, Shibata K, Terauchi M, et al. Involvement of SDF-1a/CXCR4 axis in the enhanced peritoneal metastasis of epithelial ovarian carcinoma[J]. Int J Cancer, 2008, 122(1): 91-99.
[9]
Zou W, Machelon V, Coulomb-L′Hermin A, et al. Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells[J]. Nat Med, 2001, 7(12): 1339-1346.
[10]
Balabanian K, Lagane B, Infantino S, et al. The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes[J]. J Biol Chem, 2005, 280(42): 35760-35766.
[11]
Burns JM, Summers BC, Wang Y, et al. A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development[J]. J Exp Med, 2006, 203(9): 2201-2213.
[12]
Miao Z,Luker KE,Summers BC,et al. CXCR7 (RDC1) promotes breast and lung tumor growth in vivo and is expressed on tumor associated vasculature[J]. Proc Natl Acad Sci USA, 2007, 104(40): 15735-15740.
[13]
Kurban S, Tursun M, Kurban G, et al. Role of CXCR7 and efforts on CXCL12 in Siha cells and upregulation in cervical squamous cell carinomas in Uighur women[J]. Asian Pac J Cancer Prev, 2014, 15(21): 9211-9216.
[14]
Liu Z, Yang L, Teng XY, et al. The involvement of CXCR7 in modulating the progression of papillary thyroid carcinoma[J]. J Surg Res, 2014, 191(2): 379-388.
[15]
Chow KY, Brotin E, Ben Khalifa Y, et al. A pivotal role for CXCL12 signaling in HPV-mediated transformation of keratinocytes: clues to understanding HPV-pathogenesis in WHIM syndrome[J]. Cell Host Microbe, 2010, 8(6): 523-533.
[16]
Shen-Gunther J, Wang CM, Poage GM, et al. Molecular pap smear: HPV genotype and DNA methylation of ADCY8, CDH8, and ZNF582 as an integrated biomarker for high-grade cervical cytology[J]. Clin Epigenetics, 2016, 8(1): 96-99.
[17]
Yu PF, Huang Y, Xu CL, et al. Downregulation of CXCL12 in mesenchymal stomal cells by TGF-β promotes breast cancer metastasis[J]. Oncogene, (2016-09-26)[2016-10-03].

URL    
[18]
Boldajipour B,Mahabaleshwar H,Kardash E,et al.Control of chemokine-guided cell migration by ligand sequestration[J]. Cell, 2008, 132(3): 463-473.
[19]
Wang JH, Shiozawa YS, Wang JC, et al. The role of CXCR7/RDC1 as a chemokine receptor for CXCL12/SDF-l in prostate cancer[J]. J Biol Chem, 2008, 283(7): 4283-4294.
[20]
Zur HH. Papillomaviruses and cancer: from basic studies to clinical application[J]. Nat Rev Cancer, 2002, 2(5): 342-350.
[1] Shuang Dong, Xiaoying Li, Litao Sun, Jiawei Tian. Advances in the application of imaging techniques in preoperative staging of cervical cancer[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(01): 113-119.
[2] Yimiao Wei, Yaqin Li, Weihong Zhao. Research progress on circular RNA in pathogenesis of cervical cancer[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2022, 18(05): 512-516.
[3] Lei Chu, Yi Guo, Xiaowen Tong. Research status of periostin in gynecological malignancies[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2022, 18(02): 145-149.
[4] Haixia Luo, Wei Wang, Min Hao. Current research status of gene copy number variation in cervical cancer[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2022, 18(02): 139-144.
[5] Heng Zhang, Haibo Qu. Imaging diagnosis of lymph node metastasis in cervical cancer[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2021, 17(05): 503-509.
[6] Yiran Wang, Ping Wang. Interpretation of the Guidelines of the Brazilian Society of Oncologic Surgery for Pelvic Exenteration in the Treatment of Cervical Cancer[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2021, 17(02): 142-151.
[7] Xuejiao Fan, Jianlei Bi, Lin Lin, Lin Zhao. Analysis of efficacy of neoadjuvant chemotherapy combined with surgery for stage ⅡB cervical cancer patients and its influencing factors[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2021, 17(01): 99-105.
[8] Lulu He, Qiaowen Bu, Jiaqi Luo, Jiating Gu, Xiping Luo. Current research status of methylation quantification of FAM19A4 gene promoter in cervical cancer and its precancerous lesion screening[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2021, 17(01): 23-29.
[9] Xiaoxia Zheng, Dapeng Li. Predictive values of neutrophil-to-lymphocyte ratio for neoadjuvant chemotherapy effects in patients with locally advanced cervical cancer[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2020, 16(05): 558-566.
[10] Dangyi Kong, Wei Wang, Min Hao. Evaluation value of non-coding RNA in prognosis of patients with cervical cancer[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2020, 16(05): 615-620.
[11] Yu Xue, Dan Wu, Zhunan Li, Zhengrong Zhang, Jing Lin, Ying Xu, Zhenhong Xiong, Dan Cao. Clinical effects of CO2 laser on cervical intraepithelial neoplasia and vaginal intraepithelial neoplasia[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2020, 16(04): 483-491.
[12] Xiaofei Sun, Yiqun Gu, Aichun Wang, Li Wang, Fanfan Meng, Jun Wang, lijuan Lu. Evaluation on cervical intraepithelial neoplasia for patients with cervicitis by p16/Ki-67 double staining[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2022, 16(06): 418-425.
[13] Kunpeng Wang, Yijie Yuan, Jiaqi Zhu, Tingting Zhang. Expression of LIN9 gene in cervical cancer cells and its relationship with E7 expression of human papilloma virus 16/18[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2021, 15(03): 196-201.
[14] Mi Li, huajuan Qiu, Yanqin Ji, Minghui Zhou. Effect of P16 and Ki67 expression and viral load detection on outcome of cervical lesions in woman of childbearing age with cervical intraepithelial neoplasia grade Ⅱ complicated with high-risk human papillomavirus infection[J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(03): 272-278.
[15] Ying Liu, Man Yin, Linqing Yang, Yunfei Wang. Diagnostic characteristics of invasive stratified mucin-producing carcinoma and literature review[J]. Chinese Journal of Diagnostics(Electronic Edition), 2023, 11(03): 173-177.
Viewed
Full text


Abstract