Expression and prognosis of CyclinA and CDK2 in patients with advanced cervical cancer after chemotherapy

Yongmei Gao; Hui Wang; Aizhen Zhong; Tao Yu

doi:10.14715/cmb/2020.66.3.13

Issue

Vol. 66 No. 3: Issue 3

Issue Published : June 8, 2020

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Expression and prognosis of CyclinA and CDK2 in patients with advanced cervical cancer after chemotherapy

https://doi.org/10.14715/cmb/2020.66.3.13

Yongmei Gao

Department of Gynecology, The Affiliated Qingdao Hiser Hospital of Qingdao University, Qingdao Hospital of TraditionalChinese Medicine, Qingdao 266000, China

Hui Wang

Department of Obstetrics and Gynecology, Liaocheng Third People's Hospital, Liaocheng 252000, China

Aizhen Zhong

Department of Obstetrics Zhangqiu District Maternal and Child Health Hospital, Jinan 250200, China

Tao Yu

Department of Gynecology, Zaozhuang Municipal Hospital, Zaozhuang, 277100, China

Corresponding Author(s) : Tao Yu

taoyu126@mail.ru

Cellular and Molecular Biology, Vol. 66 No. 3: Issue 3
Article Published : June 5, 2020

Abstract

This study aimed to investigate the expression and prognosis of CyclinA and CDK2 in patients with advanced cervical cancer after chemotherapy. The patient history of 108 patients with advanced cervical cancer admitted to our hospital from December 2013 to January 2016 was selected as a cervical cancer group. 54 normal healthy people admitted to our hospital for physical examination in the same period were selected as the control group. Western blotting and RT-PCR were used to detect the difference between CyclinA and CDK2 proteins and mRNA expression between the two groups and the correlation between them was analyzed. The expressions of CyclinA and CDK2 in serum and the changes in detection index level of squamous cell carcinoma antigen (SCCA), carcinoembryonic antigen (CEA) and vascular endothelial growth factor (VEGF) were observed in cervical cancer group at different stages of treatment. The correlation between the two indexes and SCCA, CEA, VEGF and the 3-year survival and prognostic significance of cervical cancer patients with different CyclinA and CDK2 expressions were analyzed. The relative expressions of CyclinA and CDK2 proteins and mRNA in the cervical cancer group were significantly higher than those in the control group (P< 0.05). Pearson correlation analysis showed a positive correlation between CyclinA and CDK2 proteins and mRNA expressions. After treatment, the expressions of CyclinA, CDK2 mRNA and SCCA, CEA and VEGF were significantly lower than those before treatment (P< 0.05). The 3-year survival rate of CyclinA and CDK2 in the high expression group was significantly lower than that of the low expression group. CyclinA and CDK2 are highly expressed in advanced cervical cancer. The expression is decreased after chemotherapy. The prognosis of both low expressions is higher and the expression is good. It can be used to predict the efficacy and prognosis of cervical cancer in the clinic.

Keywords

CyclinA CDK2 Advanced cervical cancer Chemotherapy Prognosis.

Gao, Y., Wang, H., Zhong, A., & Yu, T. (2020). Expression and prognosis of CyclinA and CDK2 in patients with advanced cervical cancer after chemotherapy. Cellular and Molecular Biology, 66(3), 85–91. https://doi.org/10.14715/cmb/2020.66.3.13

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References

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Forouzanfar MH, Foreman KJ, Delossantos AM, Lozano R, Lopez AD, Murray CJ and Naghavi M: Breast and cervical cancer in 187countries between 1980and 2010:a systematic analysis. Lancet 378: 1461-1484, 2011.
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Yoh D, Missuhiko S, S-X Jiang, et al: Active cyclin A-CDK2 Complex, a possible critical factor for cell prolifera-tion in human primary lung carcinomas. Am J Pathol 15: 963, 1998.
Dubrez L, Coll JL, Hurbin A, de Fraipont F, Lantejoul S and Favrot MC: Cell cycle arrest is suf-ficient for p53-mediated tumor regression. Gene Ther 8: 1705, 2001.
Hoei jmakers FH: Cenome maincenanee meehanisms forpreventing cancer. Nature 411: 366, 2001.
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Shin V, Ye Y, Koo M, et al: Cyclooxygenase-2 Modulated Cyclin D1, Cyclin-dependent Kinases (Cdks) and Promoted Cell Cycle Progression in Gastric Tumor Growth Stimulated by Nicotine. 2004.
Saurus P, Kuuseta S, Dumongt V, Lehtonen E, Fogarty CL, Lassenius MI, Forsblom C, Lehto M, Saleem MA, Groop PH, et al: Cyclin-dependent kinase2 protects podocytes from apoptosis. Sci Rep 6: 21664, 2016.
Cybulski M, Jarosz B, Nowakowski A, Jeleniewicz W, Kutarska E, Bednarek W and Stepulak A: Cyclin A Correlates with YB1, Progression and Resistanceto Chemotherapy in Human Epithelial Ovarian Cance. Anticancer Res 35: 1715-1721, 2016.
De Boer L, Oakes V, Beamish H, Giles N, Stevens F, Somodevilla-Torres M, Desouza C and Gabrielli B: Cyclin A/cdk2coordinateseentmsomal and nuclear mitotic events. Oncogene 27: 4261-4268, 2008.
Penson RT, Huang HQ, Wenzel LB, Monk BJ, Stockman S, Long HJ 3rd, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, et al: Bevacizumab for advanced cervical cancer:patient-reported outcomes of a randomised, phase 3 trial (NRG Oncology-Gynecologic Oncology Group protocol 240). Lancet Oncol 16: 301-311, 2015.
Mazeron R, Castelnau-Marchand P, Dumas I, del Campo ER, Kom LK, Martinetti F, Farha G, Tailleur A, Morice P, Chargari C, et al: Impact of treatment time and dose escalation on local control in locally advanced cervical cancer treated by chemoradiation and imageguided pulsed-dose rate adaptive brachytherapy. Radiother Oncol 114: 257-263, 2015.
Hernandez E, De La Mota J, Thomas MB, Huang Y, Gaughan JP and Wang F: Surgical-pathologic risk factors and immunohistochemical markers of pelvic lymph node metastasis in stage IB1 cervical cancer. J Low Genit Tract Dis 15: 303, 2011.
Dambal SK, Mihelich B, Hergenrother P, et al: Abstract 3801: Prostate cancer cells are selectively targeted by zinc-sequestration chemotherapy. Cancer Res 72: 3801-3801, 2012.
Karp G: Cell and Molecular Biology:Concepts and Experiments. 6th ed.Hoboken:John Wiley&Sons, Inc: 516, 2010.
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Tsytlonok M, Sanabria H, Wang Y, Felekyan S, Hemmen K, Phillips AH, Yun MK, Waddell MB, Park CG, Vaithiyalingam S, et al: Dynamic anticipation by Cdk2/Cyclin A-bound p27 mediates signal integration in cell cycle regulation. Nat Commun 10: 1676, 2019.
Shi XN, Li H, Yao H, Liu X, Li L, Leung KS, Kung HF and Lin MC: Adaoalene inhibits the activity of cyclin-dependent kinase 2 in colorectal carcinoma. Mol Med Rep 12: 6501-6508, 2015.
Wang X, Lu Y, Feng W, Chen Q, Guo H, Sun X and Bao Y: A two kinase-gene signature model using CDK2 and PAK4 expression predicts poor outcome in nonsmall cell lung cancers. Neoplasma 63: 322-329, 2016.
Kawana H, Tamaru J, Tanaka T, Hirai A, Saito Y, Kitagawa M, Mikata A, Harigaya K and Kuriyama T: Role of p27kip1and cyclin-dependent kinase 2 in the proliferation of non-small lung cancer. Am F Pathol 153: 505, 1998.
Dooley LM, Potts KL, Wilson LD, et al: 1187 PUBLICATION Combined therapy with radiation and S-1, an oral new 5-FU prodrug, is markedly effective against non-small cell lung cancer xenografts in mice. Eur J Cancer Suppl 3: 1656-61, 2011.
Liao B, Tang Y, Hu F, Zhou W, Yao X, Hong W, Wang J, Zhang X, Tang X and Zhang F: Serum levels of soluble vascular cell adhesion molecules may correlate with the severity of dengue viru-1 infection in adults. Emerg Microbes Infect: e24, 2015.
Parida S, Pal I, Parekh A, Thakur B, Bharti R, Das S and Mandal M: GW627368X inhibits prolif- eration and induces apoptosis in cervical cancer by interfer- ing with EP4/EGFR interactive signaling. Cell Death Dis 7: e2154, 2016.
Alotaibi MR, Gewirtz D and Povirk L: Abstract 2385: Involvement of autophagy and senescence in DNA repair in irradiated tumor cells. Cancer Res 74: 2385-2385, 2014.
Wang J, Chenivesse X, Henglein B and Bréchot C: Hepatitis B virus integration in a cyclin A gene in a hepatocellular carcinoma. Nature 343: 555-557, 1990.
Volm M and Koomgi R: Relevance of proliferative and pro-apoptotic factors in non-small-cell lung cancer for patientsurvival. Br J Cancer 82: 1747, 2000.
Tu YS, Kang XL, Zhou JG, Lv XF, Tang YB and Guan YY: Involvement of Chk1–Cdc25A-cyclin A/CDk2 pathway in simvastatin induced S-phase cell cycle arrest and apoptosis in multiple myeloma cells. Eur J Pharmacol 670: 356-364, 2011.

References

Beavis AL and Levinson KL: Preventing cervical cancer in the United States:barriers and resolutions for HPV vaccination. Front Oncol 6: 19, 2016.

Forouzanfar MH, Foreman KJ, Delossantos AM, Lozano R, Lopez AD, Murray CJ and Naghavi M: Breast and cervical cancer in 187countries between 1980and 2010:a systematic analysis. Lancet 378: 1461-1484, 2011.

Dueñas-González A and Campbell S: Global strategies for the treatment of early-stage and advanced cervical cancer. Curr Opin Obstet Gynecol 28: 11-17, 2016.

Lapresa M, Parma G, Portuesi R and Colombo N: Neoadjuvant chemotherapy in cervical cancer:an update. Expert Rev Anticancer Ther 15: 1171-1181, 2015.

Yoh D, Missuhiko S, S-X Jiang, et al: Active cyclin A-CDK2 Complex, a possible critical factor for cell prolifera-tion in human primary lung carcinomas. Am J Pathol 15: 963, 1998.

Dubrez L, Coll JL, Hurbin A, de Fraipont F, Lantejoul S and Favrot MC: Cell cycle arrest is suf-ficient for p53-mediated tumor regression. Gene Ther 8: 1705, 2001.

Hoei jmakers FH: Cenome maincenanee meehanisms forpreventing cancer. Nature 411: 366, 2001.

Dai L, Liu Y, Liu J, Wen X, Xu Z, Wang Z, Sun H, Tang S, Maguire AR, Quan J, et al: A novel cyclinE/cyclinA-CDK inhibitor targets p27(Kip1) degradation, cell cycle progression and cell survival: implications in cancer therapy. Cancer Lett 333: 103-112, 2013.

Shin V, Ye Y, Koo M, et al: Cyclooxygenase-2 Modulated Cyclin D1, Cyclin-dependent Kinases (Cdks) and Promoted Cell Cycle Progression in Gastric Tumor Growth Stimulated by Nicotine. 2004.

Saurus P, Kuuseta S, Dumongt V, Lehtonen E, Fogarty CL, Lassenius MI, Forsblom C, Lehto M, Saleem MA, Groop PH, et al: Cyclin-dependent kinase2 protects podocytes from apoptosis. Sci Rep 6: 21664, 2016.

Cybulski M, Jarosz B, Nowakowski A, Jeleniewicz W, Kutarska E, Bednarek W and Stepulak A: Cyclin A Correlates with YB1, Progression and Resistanceto Chemotherapy in Human Epithelial Ovarian Cance. Anticancer Res 35: 1715-1721, 2016.

De Boer L, Oakes V, Beamish H, Giles N, Stevens F, Somodevilla-Torres M, Desouza C and Gabrielli B: Cyclin A/cdk2coordinateseentmsomal and nuclear mitotic events. Oncogene 27: 4261-4268, 2008.

Penson RT, Huang HQ, Wenzel LB, Monk BJ, Stockman S, Long HJ 3rd, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, et al: Bevacizumab for advanced cervical cancer:patient-reported outcomes of a randomised, phase 3 trial (NRG Oncology-Gynecologic Oncology Group protocol 240). Lancet Oncol 16: 301-311, 2015.

Mazeron R, Castelnau-Marchand P, Dumas I, del Campo ER, Kom LK, Martinetti F, Farha G, Tailleur A, Morice P, Chargari C, et al: Impact of treatment time and dose escalation on local control in locally advanced cervical cancer treated by chemoradiation and imageguided pulsed-dose rate adaptive brachytherapy. Radiother Oncol 114: 257-263, 2015.

Hernandez E, De La Mota J, Thomas MB, Huang Y, Gaughan JP and Wang F: Surgical-pathologic risk factors and immunohistochemical markers of pelvic lymph node metastasis in stage IB1 cervical cancer. J Low Genit Tract Dis 15: 303, 2011.

Dambal SK, Mihelich B, Hergenrother P, et al: Abstract 3801: Prostate cancer cells are selectively targeted by zinc-sequestration chemotherapy. Cancer Res 72: 3801-3801, 2012.

Karp G: Cell and Molecular Biology:Concepts and Experiments. 6th ed.Hoboken:John Wiley&Sons, Inc: 516, 2010.

Otto T and Sicinski P: Cell cycle proteins as promising targets in cancer therapy. Nat Rev Cancer 17: 93-115, 2017.

Tsytlonok M, Sanabria H, Wang Y, Felekyan S, Hemmen K, Phillips AH, Yun MK, Waddell MB, Park CG, Vaithiyalingam S, et al: Dynamic anticipation by Cdk2/Cyclin A-bound p27 mediates signal integration in cell cycle regulation. Nat Commun 10: 1676, 2019.

Shi XN, Li H, Yao H, Liu X, Li L, Leung KS, Kung HF and Lin MC: Adaoalene inhibits the activity of cyclin-dependent kinase 2 in colorectal carcinoma. Mol Med Rep 12: 6501-6508, 2015.

Wang X, Lu Y, Feng W, Chen Q, Guo H, Sun X and Bao Y: A two kinase-gene signature model using CDK2 and PAK4 expression predicts poor outcome in nonsmall cell lung cancers. Neoplasma 63: 322-329, 2016.

Kawana H, Tamaru J, Tanaka T, Hirai A, Saito Y, Kitagawa M, Mikata A, Harigaya K and Kuriyama T: Role of p27kip1and cyclin-dependent kinase 2 in the proliferation of non-small lung cancer. Am F Pathol 153: 505, 1998.

Dooley LM, Potts KL, Wilson LD, et al: 1187 PUBLICATION Combined therapy with radiation and S-1, an oral new 5-FU prodrug, is markedly effective against non-small cell lung cancer xenografts in mice. Eur J Cancer Suppl 3: 1656-61, 2011.

Liao B, Tang Y, Hu F, Zhou W, Yao X, Hong W, Wang J, Zhang X, Tang X and Zhang F: Serum levels of soluble vascular cell adhesion molecules may correlate with the severity of dengue viru-1 infection in adults. Emerg Microbes Infect: e24, 2015.

Parida S, Pal I, Parekh A, Thakur B, Bharti R, Das S and Mandal M: GW627368X inhibits prolif- eration and induces apoptosis in cervical cancer by interfer- ing with EP4/EGFR interactive signaling. Cell Death Dis 7: e2154, 2016.

Alotaibi MR, Gewirtz D and Povirk L: Abstract 2385: Involvement of autophagy and senescence in DNA repair in irradiated tumor cells. Cancer Res 74: 2385-2385, 2014.

Wang J, Chenivesse X, Henglein B and Bréchot C: Hepatitis B virus integration in a cyclin A gene in a hepatocellular carcinoma. Nature 343: 555-557, 1990.

Volm M and Koomgi R: Relevance of proliferative and pro-apoptotic factors in non-small-cell lung cancer for patientsurvival. Br J Cancer 82: 1747, 2000.

Tu YS, Kang XL, Zhou JG, Lv XF, Tang YB and Guan YY: Involvement of Chk1–Cdc25A-cyclin A/CDk2 pathway in simvastatin induced S-phase cell cycle arrest and apoptosis in multiple myeloma cells. Eur J Pharmacol 670: 356-364, 2011.

Author biographies is not available.