Evaluation the Gene Expression of P27 and SKP2 Genes in Iraqi Women Patients with Breast Cancer

Authors

  • Israa Allawi Luaibi Al-Hraishawi Department of Medical Biotechnology, College of Biotechnology, University of Al-Qadisiyah, Iraq. Author
  • Ziad M. Alkhozai Department of Medical Biotechnology, College of Biotechnology, University of Al-Qadisiyah, Iraq. Author
  • Hadeel Jabar Neama Almuoswi Department of Medical Biotechnology, College of Biotechnology, University of Al-Qadisiyah, Iraq. Author

Keywords:

breast cancer, p27and skp2 genes.

Abstract

The current experiment has been conducted to evaluate the suppression activity of P27 and SKP2 genes by using qRT- PCR, Blood samples are taken from 60 patients' women with breast cancer to represent patients' group and 40 women without breast cancer to represent control group, the ages of both groups ranged from 30 to more than 50 years in the Al. Diwaniyah General Teaching Hospital in AL-Qadisiya province. Also, ROC curve analysis is used to demonstrate the accuracy and validity of previous parameters in detecting women with breast cancer and to estimate the sensitivity and specificity. The obtained results showed that the control group has showed significantly (p<0.01) effect on gene expression for P27 (10.882-fold change) comparison with patients groups (4.496-fold change), while the results of this study have explained that the gene expression of SKP2 for patients' group have inquired high significant (p<0.01) superiority which is 13.943-fold change compared to 3.494-fold change for control group. The age groups have no significant effect on gene expression for SKP2 and P27 genes. Analysis results of ROC curve for P27 gene expression explain it is a good indicator to detected the actually patients with breast cancer ,whereas the sensitivity and specificity is 81.7 and 22.5% respectively and the cut-off for P27 is less than 6.52 fold change, while the gene expression of SKP2 is non- efficient to detected patients with breast cancer, whereas the cut-off is more than 4.486 fold change ,the sensitivity and the specificity is 63.3 and 20%respectively. 

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References

Alkarain, A., & Slingerland, J. (2003).

Deregulation of p27 by oncogenic signaling

and its prognostic significance in breast

cancer. Breast Cancer Research, 6(1), 1-9.

Bast Jr, R. C., Ravdin, P., Hayes, D. F., Bates,

S., Fritsche Jr, H., Jessup, J. M., ... &

Somerfield, M. R. (2001). 2000 update of

recommendations for the use of tumor markers

in breast and colorectal cancer: clinical practice

guidelines of the American Society of Clinical

Oncology. Journal of clinical oncology, 19(6),

-1878.

Bencivenga, D., Tramontano, A., Borgia, A.,

Negri, A., Caldarelli, I., Oliva, A., ... &

Borriello, A. (2014). P27Kipl serine 10

phosphorylation determines its metabolism

and interaction with cyclin-dependent

kinases. Cell cycle, 13(23), 3768-3782.

Benvidi, A., Dehghani Firouzabadi, A.,

Dehghan Tezerjani, M., Moshtaghiun, S. M.,

Mazloum-Ardakani, M., & Ansarin, A. (2015).

A highly sensitive and selective

electrochemical DNA biosensor to diagnose

breast cancer. Journal of Electroanalytical

Chemistry, 750, 57—64.

Brown, I., Shalli, K., McDonald, S. L., Moir,

S. E., Hutcheon, A. W., Heys, S. D., &

Schofield, A. C. (2004). Reduced expression of

p27 is a novel mechanism of docetaxel

resistance in breast cancer cells. Breast cancer

research, 6(5), 1-7.

Cai, Z., Moten, A., Peng, D., Hsu, C. C., Pan,

B. S., Manne, R., ... & Lin, H. K. (2020,

December). The Skp2 pathway: a critical target

for cancer therapy. In Seminars in cancer

biology (Vol. 67, pp. 16-33). Academic Press.

Carrano, A. C., Eytan, E., Hershko, A., &

Pagano, M. (1999). SKP2 is required for

ubiquitin-mediated degradation of the CDK

inhibitor p27. Nature cell biology, 1(4), 193-

Catzavelos, C., Bhattacharya, N., Ung, Y. C.,

Wilson, J. A., Roncari, L., Sandhu, C., ... & Slingerland, J. M. (1997). Decreased levels of the

cell-cycle inhibitor p27 Kipl protein: prognostic

implications in primary breast cancer. Nature

medicine, 3, 227-230.

Catzavelos, C., Bhattacharya, N., Ung, Y. C.,

Wilson, J. A., Roncari, L., Sandhu, C., ... &

Slingerland, J. M. (1997). Decreased levels of the

cell-cycle inhibitor p27 Kipl protein: prognostic

implications in primary breast cancer. Nature

medicine, 3, 227-230.

Cavallaro, S., Paratore, S., de Snoo, F.,

Salomone, E., Villari, L., Buscarino, C.,

Ferraii, F., Banna, G., Furci, M., Strazzanti,

A., Cunsolo, R., Pezzino, S., Gangi, S.and

Basile, F. (2012). Genomic analysis: toward a

new approach in breast cancer management.

Crit. Rev. Oncol. Hematol., 81: 207-223

Chander, H., Halpern, M., Resnick

Silverman, L., Manfredi, J. J., & Germain, D.

(2010). Skp2B attenuates p53 function by

inhibiting prohibitin. EMBO reports, 11(3),

-225.

Chappuis, P. O., Kapusta, L., Begin, L. R.,

Wong, N., Brunet, J. S., Narod, S. A., ... &

Foulkes, W. D. (2000). Germline BRCA1/2

mutations and p27Kipl protein levels

independently predict outcome after breast

cancer. Journal of clinical oncology, 18(24),

-4052.

Coats, S., Flanagan, W. M., Nourse, J., &

Roberts, J. M. (1996). Requirement of

p27Kipl for restriction point control of the

fibroblast cell cycle. Science, 272(5263), 877-

Dahia, P. L., Aguiar, R. C., Honegger, J.,

Fahlbush, R., Jordan, S., Lowe, D. G., ... &

Grossman, A. B. (1996). Mutation and

expression analysis of the p27/kipl gene in

corticotrophin-secreting

tumours. Oncogene, 16(1), 69-76.

Gstaiger, M., Jordan, R., Lim, M.,

Catzavelos, C., Mestan, J., Slingerland, J., &

Krek, W. (2001). Skp2 is oncogenic and

overexpressed in human cancers. Proceedings

of the National Academy of Sciences, 98(9),

-5048.

Haas JS. (2005). Evaluation and outcomes of

women with a breast lump and a normal

mammogram result. J Gen Intern Med

Aug;20(8):692-6.

Habeeb,B.M.(2022). Association of ATM and

TGF 1 Genes with Breast Cancer under

Radiotherapy in a Sample of Iraqi Women

Han, S., Park, K., Kim, H. Y., Lee, M. S.,

Kim, H. J., & Kim, Y. D. (1999). Reduced

expression of p27Kipl protein is associated

with poor clinical outcome of breast cancer

patients treated with systemic chemotherapy

and is linked to cell proliferation and

differentiation. Breast cancer research and

treatment, 55, 159-165.

Hengst, L., & Reed, S. I. (1996).

Translational control of p27Kipl

accumulation during the cell

cycle. Science, 271(5257), 1861-1864.

Heravi Karimovi, M., Pourdehqan, M., Jadid

Milani, M., Foroutan, S. K., & Aieen, F. (2006).

Study of the effects of group counseling on

quality of sexual life of patients with breast

cancer under chemotherapy at Imam Khomeini

Hospital. Journal of mazandaran university of

medical sciences, 16(54), 43-51.

Hermeking, H., Lengauer, C., Polyak, K., He,

T. C., Zhang, L., Thiagalingam, S., ... &

Vogelstein, B. (1997). 14-3-3 is a p53-

regulated inhibitor of G2/M

progression. Molecular cell, 1(1), 3-11.

Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu,

J., & Thun, M. J. (2009). Cancer statistics,

CA: a cancer journal for

clinicians, 59(4), 225-249.

Joyce, C., Rayi, A., & Kasi, A. (2018). TumorSuppressor Genes.

Kamura, T., Hara, T., Kotoshiba, S., Yada,

M., Ishida, N., Imaki, H., ... & Nakayama, K.

I. (2003). Degradation of p57 Kip2 mediated

by SCFSkp2-dependent

ubiquitylation. Proceedings of the National

Academy of Sciences, 100(18), 10231-10236.

Kitagawa, M., Lee, S. H., & McCormick,

F. (2008). Skp2 suppresses p53-dependent

apoptosis by inhibiting p300. Molecular

cell, 29(2), 217-231.

Lee, J. et al. (2009) .The function of p27 KIP1

during tumor development. Exp. Mol. Med.,

, 765-771

Lin, H., Ruan, G. Y., Sun, X. Q., Chen, X. Y.,

Zheng, X., & Sun, P. M. (2019). Effects of

RNAi-induced Skp2 inhibition on cell cycle,

apoptosis and proliferation of endometrial

carcinoma cells. Experimental and

Therapeutic Medicine, 17(5), 3441-3450.

Loda, M., Cukor, B., Tam, S. W., Lavin, P.,

Fiorentinc, M., Draetta, G. F., ... & Pagano,

M. (1997). Increased proteasome-dependent

degradation of the cyclin-dependent kinase

inhibitor p27 in aggressive colorectal

carcinomas. Nature medicine, 3(2), 231-234.

Makdissi, F. B. A., Santos, S. S., Bitencourt,

A., & Campos, F. A. B. (2022). An

introduction to male breast cancer for

urologists: epidemiology, diagnosis, principles

of treatment, and special

situations. International braz j urol, 48, 760-

Mamillapalli, R., Gavrilova, N., Mihaylova, V.

T., Tsvetkov, L. M., Wu, H., Zhang, H., & Sun,

H. (2001). PTEN regulates the ubiquitin¬

dependent degradation of the CDK inhibitor

p27KIPl through the ubiquitin E3 ligase

SCFSKP2. Current Biology, 11(4), 263-267.

McCampbell, A. S., Mittelstadt, M. L., Dere,

R., Kim, S., Zhou, L., Djordjevic, B., ... &

Walker, C. L. (2016). Loss of p27 associated

with risk for endometrial carcinoma arising in

the setting of obesity. Current molecular

medicine, 16(3), 252-265.

Park, M. S., Rosai, J., Nguyen, H. T.,

Capodieci, P., Cordon-Cardo, C., & Koff, A.

(1999). p27 and Rb are on overlapping

pathways suppressing tumorigenesis in

mice. Proceedings of the National Academy of Sciences, 96(11), 6382-6387.

Porter, P. L., Malone, K. E., Heagerty, P. J.,

Alexander, G. M., Gatti, L. A., Firpo, E. J., ...

& Roberts, J. M. (1997). Expression of cell¬

cycle regulators p27 Kipl and cyclin E, alone

and in combination, correlate with survival in

young breast cancer patients. Nature

medicine, 3, 222-225.

Radke, S., Pirkmaier, A., & Germain, D.

(2005). Differential expression of the F-box

proteins Skp2 and Skp2B in breast

cancer. Oncogene, 24(21), 3448-3458.

Rivard, N., L'Allemain, G., Bartek, J., &

Pouyssegur, J. (1996). Abrogation of p27Kipl

by cDNAantisense suppresses quiescence (GO

state) in fibroblasts. Journal of Biological

Chemistry, 271(31), 18337-18341.

Russo, A. A., Jeffrey, P. D., Patten, A. K.,

Massague, J., & Pavletich, N. P. (1996).

Crystal structure of the p27Kipl cyclindependent-kinase inibitor bound to the cyclin

A—Cdk2 complex. Nature, 382(6589), 325-

Safaee, A., Zeighami, B., Tabatabaee, H. R.,

& Moghimi Dehkordi, B. (2008). Quality of

life and related factors in breast cancer

patients under chemotherapy. Iranian Journal

of Epidemiology, 3(3), 61-66.

Siegel RL, Miller KD, Fuchs HE, Jemal A.

Cancer Statistics, 2021. CA Cancer J Clin.

;71:7-33. Erratum in: CA Cancer J Clin.

;71:359.

Signoretti, S., Di Marcotullio, L., Richardson, A.,

Ramaswamy, S., Isaac, B., Rue, M., ... & Pagano,

M. (2002). Oncogenic role of the ubiquitin ligase

subunit Skp2 in human breast cancer. The Journal

of clinical investigation, 110(5), 633-641.

Singletary, S. E., Allred, C., Ashley, P.,

Bassett, L. W., Berry, D., Bland, K. L, ... &

Greene, F. L. (2003). Staging system for breast

cancer: revisions for the 6th edition of the

AJCC Cancer Staging Manual. Surgical

Clinics, 83(4), 803-819.

Soerjomataram, L, & Bray, F. (2021). Planning for tomorrow: Global cancer

incidence and the role of prevention 2020—

Nature reviews Clinical

oncology, 18(10), 663-672.

Spirin, K. S., Simpson, J. F., Takeuchi, S.,

Kawamata, N., Miller, C. W., & Koeffler, H.

P. (1996). p27/Kipl mutation found in breast

cancer. Cancer Research, 56(10), 2400-2404.

Spss,(2013).statistical pachage of social

science.version22,aplication Guide:copy

Right by spss Inc.USA.

Sung H, Ferlay J, Siegel RL, Laversanne M,

Soerjomataram I, Jemal A, et al. Global cancer

statistics 2020: GLOBOCAN estimates of

incidence and mortality worldwide for 36

cancers in 185 countries. CA Cancer J Clin.

Tan, P., Cady, B., Wanner, M., Worland, P.,

Cukor, B., Magi-Galluzzi, C., ... & Loda, M.

(1997). The cell cycle inhibitor p27 is an

independent prognostic marker in small (Tia, b)

invasive breast carcinomas. Cancer

research, 57(7), 1259-1263.

Traub, F., Mengel, M., Liick, H. J., Kreipe,

H. H., & von Wasielewski, R. (2006).

Prognostic impact of Skp2 and p27 in human

breast cancer. Breast cancer research and

treatment, 99, 185-191.

Tsuchiya, A., Zhang, G. J., & Kanno, M.

(1999). Prognostic impact of cyclin

dependent kinase inhibitor p27kipl in node

positive breast cancer. Journal of surgical

oncology, 70(4), 230-

VigBetto, G., Motti, M. L., & Fresco, A (2002).

Understanding p27kipl deregulation in cancer:

downregulation or mislocalizaiton?. Cell cycle, 1(6),

-400.Visvader, J. E„ & Stingl, J. (2014).

Mammary stem cells and the differentiation

hierarchy: current status and perspectives. Genes &

development, 28(11), 1143-1158.

Wang, Z., Fukushima, H., Inuzuka, H., Wan, L.,

Liu, P., Gao, D., ... & Wei, W. (2012). Skp2 is a

promising therapeutic target in breast

cancer. Frontiers in oncology, 1, 57.

World Health Organization ,2020.Estimated

of the new cases in 2020,worldwide New

Global Cancer Data.(WHO,2020).

Zhang, W., Cao, L., Sun, Z., Xu, J., Tang, L., Chen, W., ... & Guan, X. (2016). Skp2 is over¬ expressed in breast cancer and promotes breast cancer cell proliferation. Cell cycle, 15(10), 1344-1351.

Zhang, W., Luo, J., Chen, F., Yang, F., Song, W., Zhu, A., & Guan, X. (2015). BRCA1 regulates PIG3-mediated apoptosis in a p53- dependent manner. Oncotarget, 6(10), 76O8.Zhang, W,, Cao, L,, Sun, Z., Xu, J,, Tang, L., Chen, W., ... & Guan, X. (2016). Skp2 is over-expressed in breast cancer and promotes breast cancer cell proliferation. Cell cycle, 15(10), 1344-1351.

Zweignd, M.H.,campbell.G.(1993). Receiver operating characteristic (ROC) plots : a fundamental evaluation too in clinical medicine. clinical chemistry.,39:561-577.

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2023-02-28

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Allawi Luaibi Al-Hraishawi, I., M. Alkhozai, Z., & Jabar Neama Almuoswi, H. (2023). Evaluation the Gene Expression of P27 and SKP2 Genes in Iraqi Women Patients with Breast Cancer. History of Medicine, 9(1). http://13.200.237.241/HOM/index.php/medicine/article/view/857