Expression of Programmed Cell Death 4 in Different Subtypes of Breast Cancer and Its Relationship to Prognosis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 HANXiao-rong ¹ , WUKun-he ² , GAOHong-yi ² , LIANZhen-qiang ¹ , HANNi ¹ , HEQiu-yuan ³ ,  WANGQi ¹

1. Department of Breast Surgery, Guangdong Maternal and Children Hospital, Guangzhou 511442, Guangdong Province, China;
2. Department of Pathology, Guangdong Maternal and Children Hospital, Guangzhou 511442, Guangdong Province, China;
3. Department of Medical Records, Guangdong Maternal and Children Hospital, Guangzhou 511442, Guangdong Province, China;

Corresponding author：

WANGQi, Email: wangqigz@21cn.com

Keywords：

Breast cancer; Programmed cell death 4; Prognosis

DOI：

10.7507/1007-9424.20140139

Video：

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Objective To explore the expression of programmed cell death 4 (PDCD4) in different subtype of breast cancer and its relationship to prognosis. Methods Three hundred and thirty-eight patients with breast cancer from January 2007 to December 2009 in this hospital were collected. All these patients were categorized into three subtypes which was luminal, HER-2 positive, and triple negative according to the results of immunohistochemical stain. SP immunohistochemistry was used to detect the expression of PDCD4 in the different subtype of breast cancer. Kaplan-Meier and Cox proportional hazards model was used to analyze the prognosis. Results ①The positive rate of PDCD4 expression was 73.37%(146/199), 30.16%(19/63), and 35.53%(27/76) in the luminal, HER-2 positive, and triple negative breast cancer, respectively. The expression of PDCD4 was downregulated especially in the HER-2 positive and triple negative breast cancer(χ²=38.315, P=0.000; χ²=33.746, P=0.000) as compared with the luminal breast cancer. 2 The disease free survival and overall survival rates in the PDCD4 positive patients were significantly higher than those in the PDCD4 negative patients(P < 0.05) despite the subtypes.③Cox model revealed that T staging, N staging, and PDCD4 were the independent prognostic factors for disease free survival and that histological grade, T staging, N staging, and PDCD4 were the independent prognostic factors for overall survival. Conclusions PDCD4 expression is downregulated in all subtypes of breast cancer especially in HER-2 positive and triple negative breast cancer, and the loss of PDCD4 expression is correlated to poor prognosis. PDCD4 is an independent prognostic factor of breast cancer.

Citation： HANXiao-rong, WUKun-he, GAOHong-yi, LIANZhen-qiang, HANNi, HEQiu-yuan, WANGQi. Expression of Programmed Cell Death 4 in Different Subtypes of Breast Cancer and Its Relationship to Prognosis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2014, 21(5): 577-582. doi: 10.7507/1007-9424.20140139 Copy

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2.	Lopez KE, Toole SA, McNeil CM, et al.PI3K pathway activation in breast cancer is asociated with the basal-like phenotype and cancer-specific mortality[J].Int J Cancer, 2010, 126(5):1121-1131.
3.	Lankat-Buttgereit B, Göke R.The tumour suppressor Pdcd4:recent advances in the elucidation of function and regulation[J].Biol Cell, 2009, 101(6):309-317.
4.	Shibahara K, Asano M, Ishida Y, et al.Isolation of a novel mouse gene MA-3 that is induced upon programmed cell death[J].Gene, 1995, 166(2):297-301.
5.	Chen Y, Knösel T, Kristiansen G, et al.Loss of PDCD4 expression in human lung cancer correlates with tumour progression and prognosis[J].J Pathol, 2003, 200(5):640-646.
6.	Wei ZT, Zhang X, Wang XY, et al.Pdcd4 inhibits the malignant phenotype of ovarian cancer cells[J].Cancer Sci, 2009, 100(8):1408-1413.
7.	Zhang Z, DuBois RN.Detection of differentially expressed genes in human colon carcinoma cells treated with a selective COX-2 inhibitor[J].Oncogene, 2001, 20(33):4450-4456.
8.	Yang HS, Matthews CP, Clair T, et al.Tumorigenesis suppressor Pdcd4 down-regulates mitogen-activated protein kinase kinase kinase kinase 1 expression to suppress colon carcinoma cell invasion[J].Mol Cell Biol, 2006, 26(4):1297-1306.
9.	Wang Q, Sun Z, Yang HS.Downregulation of tumor suppressor Pdcd4 promotes invasion and activates both beta-catenin/Tcf and AP-1-dependent transcription in colon carcinoma cells[J].Oncogene, 2008, 27(11):1527-1535.
10.	Wen YH, Shi X, Chiriboga L, et al.Alterations in the expression of PDCD4 in ductal carcinoma of the breast[J].Oncol Rep, 2007, 18(6):1387-1393.
11.	González-Villasana V, Nieves-Alicea R, McMurtry V, et al.Programmed cell death 4 inhibits leptin-induced breast cancer cell invasion[J].Oncol Rep, 2012, 27(3):861-866.
12.	Nieves-Alicea R, Colburn NH, Simeone AM, et al.Programmed cell death 4 inhibits breast cancer cell invasion by increasing tissue inhibitor of metalloproteinases-2 expression[J].Breast Cancer Res Treat, 2009, 114(2):203-209.
13.	Wedeken L, Singh P, Klempnauer KH.Tumor suppressor protein Pdcd4 inhibits translation of p53 mRNA[J].J Biol Chem, 2011, 286(50):42855-42862.
14.	Palamarchuk A, Efanov A, Maximov V, et al.Akt phosphorylates and regulates Pdcd4 tumor suppressor protein[J].Cancer Res, 2005, 65(24):11282-11286.
15.	许传兵, 徐忠华, 刘照旭, 等.抑癌基因Pdcd4在肾透明细胞癌中的表达及生物学意义[J].中国现代医学杂志, 2010, 20(18):2775-2778.

1. Sørlie T, Perou CM, Tibshirani R.Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications[J].Proc Natl Acad Sci USA, 2001, 98(19):10869-10874.
2. Lopez KE, Toole SA, McNeil CM, et al.PI3K pathway activation in breast cancer is asociated with the basal-like phenotype and cancer-specific mortality[J].Int J Cancer, 2010, 126(5):1121-1131.
3. Lankat-Buttgereit B, Göke R.The tumour suppressor Pdcd4:recent advances in the elucidation of function and regulation[J].Biol Cell, 2009, 101(6):309-317.
4. Shibahara K, Asano M, Ishida Y, et al.Isolation of a novel mouse gene MA-3 that is induced upon programmed cell death[J].Gene, 1995, 166(2):297-301.
5. Chen Y, Knösel T, Kristiansen G, et al.Loss of PDCD4 expression in human lung cancer correlates with tumour progression and prognosis[J].J Pathol, 2003, 200(5):640-646.
6. Wei ZT, Zhang X, Wang XY, et al.Pdcd4 inhibits the malignant phenotype of ovarian cancer cells[J].Cancer Sci, 2009, 100(8):1408-1413.
7. Zhang Z, DuBois RN.Detection of differentially expressed genes in human colon carcinoma cells treated with a selective COX-2 inhibitor[J].Oncogene, 2001, 20(33):4450-4456.
8. Yang HS, Matthews CP, Clair T, et al.Tumorigenesis suppressor Pdcd4 down-regulates mitogen-activated protein kinase kinase kinase kinase 1 expression to suppress colon carcinoma cell invasion[J].Mol Cell Biol, 2006, 26(4):1297-1306.
9. Wang Q, Sun Z, Yang HS.Downregulation of tumor suppressor Pdcd4 promotes invasion and activates both beta-catenin/Tcf and AP-1-dependent transcription in colon carcinoma cells[J].Oncogene, 2008, 27(11):1527-1535.
10. Wen YH, Shi X, Chiriboga L, et al.Alterations in the expression of PDCD4 in ductal carcinoma of the breast[J].Oncol Rep, 2007, 18(6):1387-1393.
11. González-Villasana V, Nieves-Alicea R, McMurtry V, et al.Programmed cell death 4 inhibits leptin-induced breast cancer cell invasion[J].Oncol Rep, 2012, 27(3):861-866.
12. Nieves-Alicea R, Colburn NH, Simeone AM, et al.Programmed cell death 4 inhibits breast cancer cell invasion by increasing tissue inhibitor of metalloproteinases-2 expression[J].Breast Cancer Res Treat, 2009, 114(2):203-209.
13. Wedeken L, Singh P, Klempnauer KH.Tumor suppressor protein Pdcd4 inhibits translation of p53 mRNA[J].J Biol Chem, 2011, 286(50):42855-42862.
14. Palamarchuk A, Efanov A, Maximov V, et al.Akt phosphorylates and regulates Pdcd4 tumor suppressor protein[J].Cancer Res, 2005, 65(24):11282-11286.
15. 许传兵, 徐忠华, 刘照旭, 等.抑癌基因Pdcd4在肾透明细胞癌中的表达及生物学意义[J].中国现代医学杂志, 2010, 20(18):2775-2778.

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Expression of Programmed Cell Death 4 in Different Subtypes of Breast Cancer and Its Relationship to Prognosis

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