Clinicopathologic Significance of SATB1 and DJ-1 Proteins Expression in Cervical Carcinoma
Keywords:
Cervical Carcinoma, SATB1, DJ-1, Immunohistochemistry, Clinicopathologic Variables
Abstract
Background: Special AT-rich sequence binding protein 1 (SATB1) and DJ-1 proteins play a crucial role in tumorigenesis and tumor progression in many human malignancies. Limited data is available in literature about their role in cervical carcinomas. Aims: The present study was designed to investigate the immunohistochemical expression of SATB1 and DJ-1 proteins in cervical carcinoma and their relationships to clinicopathologic variables. Material and Methods: Tissue sections from 100 cervical lesions distributed as 60 cases of cervical carcinoma, 30 cases of squamous intraepithelial lesion (SIL) and 10 cases with normal cervical tissue were evaluated for SATB1 and DJ-1 proteins expression by immunohistochemistry. Results: SATB1 expression was detected in 41.7% of cervical carcinomas versus 20% and 6.7% of HSIL and LSIL, respectively (p = 0.019). A significant positive correlation between SATB1 expression to lymph node metastasis (p = 0.004) and pTNM (p = 0.028) was noted. DJ-1 expression was detected in 68.3% versus 33.3% and 13.3% of HSIL and LSIL, respectively (p = 0.001). A significant positive association between DJ-1 expression and lymph node metastasis (p = 0.037) was noted. Normal cervical tissue was negative for SATB1 and DJ-1 expression. A significant positive association between SATB1 and DJ-1 immunoreactivity was detected in investigated cervical carcinomas (p = 0.027). Conclusions: SATB1 and DJ-1 are shown to be promising potential prognostic biomarkers in cervical carcinoma since their overexpression is correlated with advanced clinicopathologic variables including lymph node metastasis. SATB1 and DJ-1 can be promising therapeutic targets for cervical cancer.References
1- Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr.
2- Wang S, Wang L, Zhang Y, Liu Y, Meng F, Ma J, et al. Special AT-rich sequence-binding protein 1: a novel biomarker predicting cervical squamous cell carcinoma prognosis and lymph node metastasis. Jpn J Clin Oncol. 2015; 45(9):812-818.
3- Alvarez JD, Yasui DH, Niida H, Joh T, Loh DY, Kohwi-Shigematsu T: The MAR-binding protein SATB1 orchestrates temporal and spatial expression of multiple genes during T-cell development. Genes Dev. 2000; 14:521–535.
4- Cai S, Han HJ, Kohwi-Shigematsu T. Tissue-specific nuclear architecture and gene expression regulated by SATB1. Nat Genet. 2003; 34:42-51.
5- Galande S, Purbey PK, Notani D, Kumar PP: The third dimension of gene regulation: organization of dynamic chromatin loopscape by SATB1. Curr Opin Genet Dev. 2007; 17:408–414.
6- Zhang S, Gao X, Ma Y, Jiang J, Dai Z, Yin X, et al. Expression and significance of SATB1 in the development of breast cancer. Genet Mol Res. 2015; 14(2):3309-3317.
7- Ismail IA, Kang HS, Lee HJ, Kim JK, Hong SH. DJ-1 upregulates breast cancer cell invasion by repressing KLF17 expression. Br J Cancer 2014; 110:1298-1306.
8- Wang B, Qin H, Wang Y, Chen W, Luo J, Zhu X, et al. Effect of DJ-1 overexpression on the proliferation, apoptosis, invasion and migration of laryngeal squamous cell carcinoma SNU-46 cells through PI3K/AKT/mTOR. Oncol Rep. 2014; 32(3):1108-1116.
9- Cao J, Lou S , Ying M, Yang B. DJ-1 as a human oncogene and potential therapeutic target. Biochemical Pharmacology 2015; 93: 241–250.
10- Kim RH, Peters M, Jang Y, Shi W, Pintilie M, Fletcher GC, et al. DJ-1, a novel regulator of the tumor suppressor PTEN. Cancer Cell 2005; 7: 263-273.
11- Kurman RJ, Caracangiu ML, Herrington CS and Young RH, “World Health Organization Classification of Tumors: WHO Classification of Tumors of Female Reproductive Organs”, 4th edition, Lyon: IARC press, 2014; pp 170-171.
12- Patani N, Jiang W, Mansel R, Newbold R, Mokbel K. The mRNA expression of SATB1 and SATB2 in human breast cancer. Cancer Cell Int. 2009; 9:18.
13- Mao L, Yang C, Wang J, Li W, Wen R, Chen J, et al. SATB1 is overexpressed in metastatic prostate cancer and promotes prostate cancer cell growth and invasion. J Transl Med. 2013; 11:111.
14- Han HJ, Russo J, Kohwi Y, Kohwi-Shigematsu T: SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis. Nature 2008; 452(7184):187-193.
15- Lu X, Cheng C, Zhu S, Yang Y, Zheng L, Wang G, et al. SATB1 is an independent prognostic marker for gastric cancer in a Chinese population. Oncol Rep. 2010; 24(4):981-987.
16- Zhang Y, Tian X, Ji H, Guan X, Xu W, Dong B, et al. Expression of SATB1 promotes the growth and metastasis of colorectal cancer. PLoS One. 2014; 9(6):e100413.
17- Wu D, Zeng L, Liu F, Zhong Q, Zhang D, Cai C, et al. Special AT rich DNA binding protein 1 expression is associated with liver cancer metastasis. Oncol Lett. 2016; 12(6):4377-4384.
18- Xiang J, Zhou L, Li S, Xi X, Zhang J, Wang Y, et al. AT-rich sequence binding protein 1: contribution to tumor progression and metastasis of human ovarian carcinoma. Oncol Lett. 2012; 3(4):865-870.
19- Zhao XD, Ji WY, Zhang W, He LX, Yang J, Liang HJ, et al. Overexpression of SATB1 in laryngeal squamous cell carcinoma. ORL J Otorhinolaryngol Relat Spec. 2010; 72(1):1-5.
20- Chen H, Takahara M, Oba J, Xie L, Chiba T, Takeuchi S, et al. Clinicopathologic and prognostic significance of SATB1 in cutaneous malignant melanoma. J Dermatol Sci. 2011; 64(1):39-44.
21- He X, Zheng Z, Li J, Ben Q, Liu J, Zhang J, et al. DJ-1 promotes invasion and metastasis of pancreatic cancer cells by activating SRC/ERK/uPA. Carcinogenesis. 2012; 33(3):555-562.
22- Vasseur S, Afzal S, Tardivel-Lacombe J, Park DS, Iovanna JL, Mak TW. DJ-1/PARK7 is an important mediator of hypoxia-induced cellular responses. Proc Natl Acad Sci U S A. 2009; 106:1111-1116.
23- Shen Z, Ren Y, Ye D, Guo J, Kang C, Ding H. Significance and relationship between DJ-1 gene and surviving gene expression in laryngeal carcinoma. Eur J Histochem. 2011; 55:e9.
24- Shu K, Xiao Z, Long S, Yan J, Yu X, Zhu Q, Mei T. Expression of DJ-1 in endometrial cancer close correlation with clinicopathological features and apoptosis. Int J Gynecol Cancer. 2013; 23:1029-35.
25- Li Y, Cui J, Zhang CH, Yang DJ, Chen JH, Zan WH, et al. High-expression of DJ-1 and loss of PTEN associated with tumor metastasis and correlated with poor prognosis of gastric carcinoma. Int J Med Sci. 2013; 10:1689-1697.
26- Lee H, Choi SK, Ro JY. Overexpression of DJ-1 and HSP90α, and loss of PTEN associated with invasive urothelial carcinoma of urinary bladder: Possible prognostic markers. Oncol Lett. 2012; 3:507-512.
27- Sun Y-H, Wen W, Song J-M, Xu M-Q, Yang Z-Y. Expression of DJ-1 in human cervical lesion tissues and its clinical significance. Chinese J. Diagn. Pathol. 2013; 3. Abstract (available in English on website: en.cnki.com.cn/Article_en/CJFDTOTAL-ZDBL201303014.htm).
28- Arnouk H, Merkley MA, Podolsky RH, Stöppler H, Santos C, Alvarez M, et al. Characterization of Molecular Markers Indicative of cervical Cancer Progression. Proteomics Clin Appl. 2009; 3:516-527.
29- Wang H, Gao W. DJ-1 Expression in Cervical Carcinoma and its Effects on Cell Viability and Apoptosis. Med Sci Monit, 2016; 22: 2943-2949.
2- Wang S, Wang L, Zhang Y, Liu Y, Meng F, Ma J, et al. Special AT-rich sequence-binding protein 1: a novel biomarker predicting cervical squamous cell carcinoma prognosis and lymph node metastasis. Jpn J Clin Oncol. 2015; 45(9):812-818.
3- Alvarez JD, Yasui DH, Niida H, Joh T, Loh DY, Kohwi-Shigematsu T: The MAR-binding protein SATB1 orchestrates temporal and spatial expression of multiple genes during T-cell development. Genes Dev. 2000; 14:521–535.
4- Cai S, Han HJ, Kohwi-Shigematsu T. Tissue-specific nuclear architecture and gene expression regulated by SATB1. Nat Genet. 2003; 34:42-51.
5- Galande S, Purbey PK, Notani D, Kumar PP: The third dimension of gene regulation: organization of dynamic chromatin loopscape by SATB1. Curr Opin Genet Dev. 2007; 17:408–414.
6- Zhang S, Gao X, Ma Y, Jiang J, Dai Z, Yin X, et al. Expression and significance of SATB1 in the development of breast cancer. Genet Mol Res. 2015; 14(2):3309-3317.
7- Ismail IA, Kang HS, Lee HJ, Kim JK, Hong SH. DJ-1 upregulates breast cancer cell invasion by repressing KLF17 expression. Br J Cancer 2014; 110:1298-1306.
8- Wang B, Qin H, Wang Y, Chen W, Luo J, Zhu X, et al. Effect of DJ-1 overexpression on the proliferation, apoptosis, invasion and migration of laryngeal squamous cell carcinoma SNU-46 cells through PI3K/AKT/mTOR. Oncol Rep. 2014; 32(3):1108-1116.
9- Cao J, Lou S , Ying M, Yang B. DJ-1 as a human oncogene and potential therapeutic target. Biochemical Pharmacology 2015; 93: 241–250.
10- Kim RH, Peters M, Jang Y, Shi W, Pintilie M, Fletcher GC, et al. DJ-1, a novel regulator of the tumor suppressor PTEN. Cancer Cell 2005; 7: 263-273.
11- Kurman RJ, Caracangiu ML, Herrington CS and Young RH, “World Health Organization Classification of Tumors: WHO Classification of Tumors of Female Reproductive Organs”, 4th edition, Lyon: IARC press, 2014; pp 170-171.
12- Patani N, Jiang W, Mansel R, Newbold R, Mokbel K. The mRNA expression of SATB1 and SATB2 in human breast cancer. Cancer Cell Int. 2009; 9:18.
13- Mao L, Yang C, Wang J, Li W, Wen R, Chen J, et al. SATB1 is overexpressed in metastatic prostate cancer and promotes prostate cancer cell growth and invasion. J Transl Med. 2013; 11:111.
14- Han HJ, Russo J, Kohwi Y, Kohwi-Shigematsu T: SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis. Nature 2008; 452(7184):187-193.
15- Lu X, Cheng C, Zhu S, Yang Y, Zheng L, Wang G, et al. SATB1 is an independent prognostic marker for gastric cancer in a Chinese population. Oncol Rep. 2010; 24(4):981-987.
16- Zhang Y, Tian X, Ji H, Guan X, Xu W, Dong B, et al. Expression of SATB1 promotes the growth and metastasis of colorectal cancer. PLoS One. 2014; 9(6):e100413.
17- Wu D, Zeng L, Liu F, Zhong Q, Zhang D, Cai C, et al. Special AT rich DNA binding protein 1 expression is associated with liver cancer metastasis. Oncol Lett. 2016; 12(6):4377-4384.
18- Xiang J, Zhou L, Li S, Xi X, Zhang J, Wang Y, et al. AT-rich sequence binding protein 1: contribution to tumor progression and metastasis of human ovarian carcinoma. Oncol Lett. 2012; 3(4):865-870.
19- Zhao XD, Ji WY, Zhang W, He LX, Yang J, Liang HJ, et al. Overexpression of SATB1 in laryngeal squamous cell carcinoma. ORL J Otorhinolaryngol Relat Spec. 2010; 72(1):1-5.
20- Chen H, Takahara M, Oba J, Xie L, Chiba T, Takeuchi S, et al. Clinicopathologic and prognostic significance of SATB1 in cutaneous malignant melanoma. J Dermatol Sci. 2011; 64(1):39-44.
21- He X, Zheng Z, Li J, Ben Q, Liu J, Zhang J, et al. DJ-1 promotes invasion and metastasis of pancreatic cancer cells by activating SRC/ERK/uPA. Carcinogenesis. 2012; 33(3):555-562.
22- Vasseur S, Afzal S, Tardivel-Lacombe J, Park DS, Iovanna JL, Mak TW. DJ-1/PARK7 is an important mediator of hypoxia-induced cellular responses. Proc Natl Acad Sci U S A. 2009; 106:1111-1116.
23- Shen Z, Ren Y, Ye D, Guo J, Kang C, Ding H. Significance and relationship between DJ-1 gene and surviving gene expression in laryngeal carcinoma. Eur J Histochem. 2011; 55:e9.
24- Shu K, Xiao Z, Long S, Yan J, Yu X, Zhu Q, Mei T. Expression of DJ-1 in endometrial cancer close correlation with clinicopathological features and apoptosis. Int J Gynecol Cancer. 2013; 23:1029-35.
25- Li Y, Cui J, Zhang CH, Yang DJ, Chen JH, Zan WH, et al. High-expression of DJ-1 and loss of PTEN associated with tumor metastasis and correlated with poor prognosis of gastric carcinoma. Int J Med Sci. 2013; 10:1689-1697.
26- Lee H, Choi SK, Ro JY. Overexpression of DJ-1 and HSP90α, and loss of PTEN associated with invasive urothelial carcinoma of urinary bladder: Possible prognostic markers. Oncol Lett. 2012; 3:507-512.
27- Sun Y-H, Wen W, Song J-M, Xu M-Q, Yang Z-Y. Expression of DJ-1 in human cervical lesion tissues and its clinical significance. Chinese J. Diagn. Pathol. 2013; 3. Abstract (available in English on website: en.cnki.com.cn/Article_en/CJFDTOTAL-ZDBL201303014.htm).
28- Arnouk H, Merkley MA, Podolsky RH, Stöppler H, Santos C, Alvarez M, et al. Characterization of Molecular Markers Indicative of cervical Cancer Progression. Proteomics Clin Appl. 2009; 3:516-527.
29- Wang H, Gao W. DJ-1 Expression in Cervical Carcinoma and its Effects on Cell Viability and Apoptosis. Med Sci Monit, 2016; 22: 2943-2949.
Published
2018-08-31
Issue
Section
Original Article
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access at http://opcit.eprints.org/oacitation-biblio.html).
