BRMS1 Gene Expression May Be Associated with Clinico-Pathological Features of Breast Cancer
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Bioscience Reports (2017) 37 BSR20170672 DOI: 10.1042/BSR20170672 Research Article BRMS1 gene expression may be associated with clinico-pathological features of breast cancer Li-Zhong Lin1, Miao-Guo Cai2, Yue-Chu Dai1, Zhi-Bao Zheng1, Fang-Fang Jiang1, Li-Li Shi3,YinPan1 and Han-Bing Song3 1Department of Oncology, Taizhou Central Hospital, Taizhou 318000, P.R. China; 2Department of Oncology, Luqiao Branch of Taizhou Hospital, Taizhou 318000, P.R. China; Downloaded from http://portlandpress.com/bioscirep/article-pdf/37/4/BSR20170672/480548/bsr-2017-0672.pdf by guest on 30 September 2021 3Department of Infection, Luqiao Branch of Taizhou Hospital, Taizhou 318000, P.R. China Correspondence: Yin Pan ([email protected]) Our aim is to investigate whether or not the breast cancer metastasis suppressor 1 (BRMS1) gene expression is directly linked to clinico-pathological features of breast cancer. Following a stringent inclusion and exclusion criteria, case–control studies with associations between BRMS1 and breast cancer were selected from articles obtained by way of searches con- ducted through an electronic database. All statistical analyses were performed with Stata 12.0 (Stata Corp, College Station, TX, U.S.A.). Ultimately, 1,263 patients with breast can- cer were found in a meta-analysis retrieved from a total that included 12 studies. Results of our meta-analysis suggested that BRMS1 protein in breast cancer tissues was signifi- cantly lower in comparison with normal breast tissues (odds ratio, OR = 0.08, 95% confi- dence interval (CI) = 0.04–0.15). The BRMS1 protein in metastatic breast cancer tissue was decreased than from that was found in non-metastatic breast cancer tissue (OR = 0.20, 95%CI = 0.13–0.29), and BRMS1 protein in tumor-node-metastasis (TNM) stages 1 and 2 was found to be higher than TNM stages 3 and 4 (OR = 4.62, 95%CI = 2.77–7.70). BRMS1 protein in all three major types of breast cancer was lower than that of control tissues re- spectively. We also found strong correlations between BRMS1 mRNA levels and TNM stage and tumor size. The results our meta-analysis showed that reduction in BRMS1 expression level was linked directly to clinico-pathological features of breast cancer significantly; there- fore, suggesting the loss of expression or reduced levels of BRMS1 is potentially a strong indicator of the metastatic capacity of breast cancer with poor prognosis. Introduction Breast cancer accounts for approximately33% of cancers diagnosed among females in the U.S.A., and is the secondleading cause of cancer deaths worldwide[1]. Generally, older women are more commonly diagnosed with breast cancer, with one in 200 women before the age of 40 being diagnosed [2]. Generally, approximately 40% of all patients with breast cancer experience a relapse, of which recurrences 10–20% are locallymetastaticand 60–70% are distant metastases [3].Theestablished risk factors for breast cancer are age, menopausal status, bodymassindex (BMI), duration of breastfeeding, age at first pregnancy, and postmenopausal hormonal use [4-6].Thepredominant cause of death in breast cancer is distant metastasis Received: 12 April 2017 [7]. Tumor metastasis is a multistep process involving disruption of intercellular adhesions anddispersal Revised: 18 May 2017 of singlecellsfromsolid tumor, invasion of blood andlymphatic vessels, immunologic escape in circula- Accepted: 22 May 2017 tion, attachment to endothelial cells, extravasation from blood andlymph vesselsand proliferation, and angiogenesis induction [8,9]. This process is assisted by a preferred microenvironment at the primary and Accepted Manuscript Online: 22 May 2017 metastatic sites [7]. Version of Record published: Breast cancer metastasis suppressor 1 (BRMS1), introduced in 2000,inhibitsmetastasiswhilehaving 21 August 2017 no effect on the growth of primary tumors [10].TheBRMS1 gene is located at 11q13.1-13.2, a region c 2017 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution 1 License 4.0 (CC BY). Bioscience Reports (2017) 37 BSR20170672 DOI: 10.1042/BSR20170672 A BRMS1 postive rate (Breast cancer tissue VS. healthy control) Included study OR (95% CI) Weight% Wang DY (2014) 0.03 (0.01, 0.12) 44.10 Wu ZY (2011) 0.14 (0.04, 0.50) 18.22 He XB (2009) 0.06 (0.01, 0.27) 20.71 Cui M (2009) 0.17 (0.05, 0.54) 16.98 Heterogeneity test (I2 = 32.1%, P = 0.219) 0.08 (0.04, 0.15) 100.00 Z test (Z = 7.67, P < 0.001) Downloaded from http://portlandpress.com/bioscirep/article-pdf/37/4/BSR20170672/480548/bsr-2017-0672.pdf by guest on 30 September 2021 0.00641 1 156 B BRMS1 mRNA level (Breast cancer tissue VS. healthy control) Included study SMD (95% CI) Weight% Tang LB (2007) −12.00 (−13.44, −10.55) 49.80 Zhang YL (2006) −0.97 (−1.38, −0.56) 50.20 Heterogeneity test (I2 = 99.5%, P < 0.001) −6.46 (−17.27, 4.34) 100.00 Z test (Z = 1.17, P = 0.241) Random effects analysis −17.3 0 17.3 Figure 1. The expressions of BRMS1 in breast cancer and healthy tissues. often altered in late-stage breast cancers, whileinclose proximity to the genomic loci that contains deletions and amplifications commonlyobserved in progression of breast cancer [11].BRMS1 is also an inhibitor of metastasis in ovarian cancer, bladder cancer, non-small cell lung cancer, melanoma, and breast cancer. Metastasis mouse models have demonstrated ahighcapacityforBRMS1 to inhibit metastasis, recording up to 80–90% metastasis inhibition [8,12,13].ThemechanismsbywhichBRMS1 mediates its anti-metastasis function still remain unknown despite observations of anti-metastatic potential of BRMS1 [7].Following this context, it is also important that thorough evaluation of the BRMS1 association with metastatic breast cancer is performed, so for this reason performing a meta-analysis based studytotestthecorrelation between BRMS1 expression and the tumor behavior in breast cancers alone was necessary. Materials and methods Search strategy A literature search was performed systematically using PubMed,EBSCO, SpringerLink, Wiley, Ovid, Web of science, Wanfang Database, China National Knowledge Infrastructure (CNKI), andVIP Information databases using MeSH and free text search terms (last updated search on October, 2014). All variantsofkeysearchterms: breast cancer and BRMS1were included. For example, (‘BRMS1 protein, human’ or ‘breast-cancer metastasis suppressor 1’)and (‘breast neoplasms’ or ‘breast cancer’ or ‘breast carcinoma’ or ‘tumors, breast’ or ‘mammary neoplasms, human’ or ‘carcinoma, human mammary’ or ‘mammary cancer’ or ‘malignant neoplasmofbreast’ or ‘malignant tumor of breast’ or ‘cancer of the breast’)wereselected to retrieve corresponding literatures. Bibliographies regarding the collected trialsand review papers were studied and explored manuallyforpotentiallyrelevant and conducive articles. Criteria for selecting articles included in this meta-analysis Studyarticles were incorporated if (1)thestudytypeofselected studies was case–control study; (2) studysubjects were patients diagnosed with breast cancer and healthy controls; (3) selected studies provided complete data consisting of sample size, age, ethnicity, gender, pathological types, positive expression rate of BRMS1 protein, expression of BRMS1 mRNA etc.; (4) the extracted studies were published by the same authors, onlyincluding the last or complete one. 2 c 2017 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY). Bioscience Reports (2017) 37 BSR20170672 DOI: 10.1042/BSR20170672 A B BRMS1 postive rate BRMS1 postive rate (LN Present VS. LN Absent) (TNM I/II stage VS. TNM III/IV stage) Included study OR (95% CI) Weight% Included study OR (95% CI) Weight% Wang DY (2014) 0.38 (0.20, 0.73) 25.22 Wang DY (2014) 3.98 (1.80, 8.83) 44.03 Wang LX (2013) 0.08 (0.02, 0.29) 15.66 Wu ZY (2011) 4.38 (1.47, 13.05) 20.25 Han DY (2012) 0.15 (0.05, 0.41) 16.80 He XB (2009) 4.36 (1.32, 14.45) 19.77 Wu ZY (2011) 0.19 (0.06, 0.68) 10.74 He XB (2009) 0.16 (0.05, 0.49) 14.65 Cui M (2009) 7.00 (2.13, 23.02) 15.95 Cui M (2009) 0.12 (0.04, 0.37) 16.94 Heterogeneity test (I2 = 0.00%, P = 0.892) 4.62 (2.77, 7.70) 100.00 2 Heterogeneity test (I = 27.5%, P = 0.229) 0.20 (0.13, 0.29) 100.00 Z test (Z = 5.87, P < 0.001) Z test (Z = 8.05, P < 0.001) 0.023 1 43.4 0.0434 1 23 C D BRMS1 postive rate BRMS1 postive rate (Big tumors VS. Small tumors) (Histological I/II grade VS. Histological III grade) Included study OR (95% CI) Weight% Included study OR (95% CI) Weight% Downloaded from http://portlandpress.com/bioscirep/article-pdf/37/4/BSR20170672/480548/bsr-2017-0672.pdf by guest on 30 September 2021 Wang DY (2014) 1.26 (0.66, 2.42) 29.33 Wang DY (2014) 1.38 (0.72, 2.65) 41.08 Han DY (2012) 1.25 (0.49, 3.17) 14.44 Han DY (2012) 1.25 (0.50, 3.16) 21.17 Wu ZY (2011) 0.66 (0.23, 1.92) 15.29 He XB (2009) 1.30 (0.47, 3.54) 17.91 He XB (2009) 1.04 (0.41, 2.63) 15.69 Cui M (2009) 1.32 (0.51, 3.41) 19.84 Cui M (2009) 0.43 (0.17, 1.07) 25.26 Heterogeneity test (I2 = 0.00%, P = 0.998) 1.33 (0.87, 2.02) 100.00 Heterogeneity test (I2 = 10.2%, P = 0.348) 0.92 (0.63, 1.35) 100.00 Z test (Z = 1.31, P = 0.190) Z test (Z = 0.42, P = 0.673) 0.171 1 5.86 0.282 1 3.54 Figure 2.