Relations between SCUBE3 or SP1 expression and clinicopathologic characteristics and prognosis of patients with breast cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

YUAN Qinghui ¹ , XIE Gang ¹ , WANG Anqun ¹ ,  HE Wei ²

1. Department of Pathology, Mianyang Central Hospital, Mianyang, Sichuan 621000, P. R. China;
2. Department of Pain, Mianyang Central Hospital, Mianyang, Sichuan 621000, P. R. China;

Corresponding author：

HE Wei, Email: hewei5413@163.com

Keywords：

breast cancer; signal peptide-CUB-EGF-like domain containing protein 3; specificity protein 1; clinicopathologic characteristics; prognosis

DOI：

10.7507/1007-9424.202104051

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Objective To detect the expressions of signal peptide-CUB-EGF-like domain containing protein 3 (SCUBE3) and specificity protein 1 (SP1) in breast cancer tissues, and explore relations between their protein expressions and clinicopathologic features or prognosis.Methods From February 2013 to October 2015, the breast cancer tissues and the corresponding adjacent normal breast tissues of 80 women patients with breast cancer in the Mianyang Central Hospital were selected, and the expressions of SCUBE3 and SP1 proteins in the tissues were detected by immunohistochemistry. The relations between the expressions of SCUBE3 and SP1 and clinicopathologic parameters of breast cancer were analyzed, the correlation between the SCUBE3 and SP1 was analyzed by Spearman rank correlation analysis. Kaplan-Meier method was used to analyze the survival of patients with breast cancer; and Cox proportional hazards regression model was used to analyze the risk factors of overall survival of patients with breast cancer.Results The positive rates of SCUBE3 and SP1 proteins expressions in the breast cancer tissues were higher than those in the corresponding adjacent normal breast tissues (P<0.05). The positive rates of SCUBE3 and SP1 protein expressions were higher in the breast cancer tissues with lymph node metastasis and molecular subtypes of Luminal A or B (P<0.05), and the positive rates of SCUBE3 protein expression were higher in the breast cancer tissues with TNM stage Ⅱ–Ⅳ and high Ki67 (P<0.05). The retsult of Spearman rank correlation analysis showed that the positive rates of SCUBE3 and SP1 proteins expressions in the breast cancer tissues was positive correlation (χ²=7.979, r_s=0.316, P=0.005). Kaplan-Meier curve showed that the overall survival of the patients with positive expression of SCUBE3 or SP1 protein was worse than that of the patients with negative expression (χ²=4.042, P=0.044; χ²=10.676, P=0.001). The Cox proportional hazards regression model multivariate analysis showed that the positive SCUBE3 (HR=6.020, P=0.016), positive SP1 (HR=4.077, P=0.018), lymph node metastasis (HR=3.518, P=0.017), and higher Ki67 expression (HR=7.989, P<0.001) were the independent risk factors of overall survival for the patients with breast cancer.Conclusion Positive rates of SCUBE3 and SP1 proteins expressions in breast cancer tissues are higher and there is a positive correlation between them, which are closely related to clinicopathologic parameters such as lymph node metastasis and molecular subtypes and prognosis of patients with breast cancer.

Citation： YUAN Qinghui, XIE Gang, WANG Anqun, HE Wei. Relations between SCUBE3 or SP1 expression and clinicopathologic characteristics and prognosis of patients with breast cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2022, 29(1): 72-77. doi: 10.7507/1007-9424.202104051 Copy

1.	康佳, 吴桐, 张蕾, 等. 不同分子分型乳腺癌的多模态超声特征和临床病理对照研究. 中华超声影像学杂志, 2020, 29(4): 330-336.
2.	Kayali M, Abi Jaoude J, Tfayli A, et al. Post-mastectomy radiation therapy in breast cancer patients with 1–3 positive lymph nodes: No one size fits all. Crit Rev Oncol Hematol, 2020, 147: 102880.
3.	邱鹏飞, 王永胜. 乳腺癌内乳淋巴结精准分期与个体化治疗. 中国肿瘤外科杂志, 2020, 12(4): 306-310, 315.
4.	Andersson Y, Bergkvist L, Frisell J, et al. Long-term breast cancer survival in relation to the metastatic tumor burden in axillary lymph nodes. Breast Cancer Res Treat, 2018, 171(2): 359-369.
5.	Wu YY, Peck K, Chang YL, et al. SCUBE3 is an endogenous TGF-β receptor ligand and regulates the epithelial-mesenchymal transition in lung cancer. Oncogene, 2011, 30(34): 3682-3693.
6.	Liu X, Wang LG, Zhang LC, et al. Molecular cloning, tissue expression pattern, and copy number variation of porcine SCUBE3. Genet Mol Res, 2016, 15(1): gmr7010.
7.	Huo Q, He X, Li Z, et al. SCUBE3 serves as an independent poor prognostic factor in breast cancer. Cancer Cell Int, 2021, 21(1): 268.
8.	孔祥泉, 曾毅, 王立峰, 等. 乳腺癌组织中 SCUBE2 表达与临床病理特征的相关性研究. 慢性病学杂志, 2016, 17(8): 845-849.
9.	Torabi B, Flashner S, Beishline K, et al. Caspase cleavage of transcription factor Sp1 enhances apoptosis. Apoptosis, 2018, 23(1): 65-78.
10.	Zhang KF, Wang J, Guo J, et al. Metformin enhances radiosensitivity in hepatocellular carcinoma by inhibition of specificity protein 1 and epithelial-to-mesenchymal transition. J Cancer Res Ther, 2019, 15(7): 1603-1610.
11.	史晓宇, 张敬, 孟玮, 等. 转录因子 Sp1 和存活素在乳腺癌中的表达及相关性研究. 实用肿瘤学杂志, 2017, 31(2): 107-111.
12.	刘裔莎, 魏兵, 杨雯娟, 等. 美国癌症联合会乳腺癌分期(第七版)简介. 中华病理学杂志, 2010, 39(11): 787-790.
13.	Bliss SA, Paul S, Pobiarzyn PW, et al. Evaluation of a developmental hierarchy for breast cancer cells to assess risk-based patient selection for targeted treatment. Sci Rep, 2018, 8(1): 367.
14.	卢小冬. 长链非编码 RNA 牛磺酸调节基因 1 和 miR-132 的表达与乳腺癌预后的关系. 中华普通外科学文献(电子版), 2020, 14(1): 5-9.
15.	Said NM. Three gold indicators for breast cancer prognosis: a case-control study with ROC analysis for novel ratios related to CBC with (ALP and LDH). Mol Biol Rep, 2019, 46(2): 2013-2027.
16.	Su F, Geng J, Li X, et al. SP1 promotes tumor angiogenesis and invasion by activating VEGF expression in an acquired trastuzumab-resistant ovarian cancer model. Oncol Rep, 2017, 38(5): 2677-2684.
17.	Bolayır HA, Güneş H, Kıvrak T, et al. The role of SCUBE1 in the pathogenesis of no-reflow phenomenon presenting with ST segment elevation myocardial infarction. Anatol J Cardiol, 2017, 18(2): 122-127.
18.	Yang X, Hu J, Shi C, et al. Activation of TGF-β1 pathway by SCUBE3 regulates TWIST1 expression and promotes breast cancer progression. Cancer Biother Radiopharm, 2020, 35(2): 120-128.
19.	李俊, 李国庆. 新型分泌型蛋白 SCUBE1 在急性冠脉综合征中促进无复流的研究进展. 新疆医学, 2018, 48(1): 91-93.
20.	Chen JH, Kuo KT, Bamodu OA, et al. Upregulated SCUBE2 expression in breast cancer stem cells enhances triple negative breast cancer aggression through modulation of Notch signaling and epithelial-to-mesenchymal transition. Exp Cell Res, 2018, 370(2): 444-453.
21.	Monteleone E, Orecchia V, Corrieri P, et al. SP1 and STAT3 functionally synergize to induce the RhoU small GTPase and a subclass of non-canonical WNT responsive genes correlating with poor prognosis in breast cancer. Cancers (Basel), 2019, 11(1): 101.
22.	韩亮, 张丽荣, 赵峰. 转录因子特异性蛋白 1 对三阴乳腺癌 HCC1806 细胞增殖凋亡的影响及其机制. 中华实验外科杂志, 2020, 37(7): 1201-1204.
23.	Lee YJ, Kim WI, Kim SY, et al. Flavonoid morin inhibits proliferation and induces apoptosis of melanoma cells by regulating reactive oxygen species, Sp1 and Mcl-1. Arch Pharm Res, 2019, 42(6): 531-542.
24.	黎三艳, 郑眉嵩, 陈余鹏, 等. 孕激素抗体 EP2、SP2、1E2、16 在非特殊型浸润性乳腺癌的表达差异. 第三军医大学学报, 2020, 42(10): 1042-1046.
25.	Zhang S, Huang P, Dai H, et al. Timeless regulates sphingolipid metabolism and tumor cell growth through Sp1/ACER2/S1P axis in ER-positive breast cancer. Cell Death Dis, 2020, 11(10): 892.

1. 康佳, 吴桐, 张蕾, 等. 不同分子分型乳腺癌的多模态超声特征和临床病理对照研究. 中华超声影像学杂志, 2020, 29(4): 330-336.
2. Kayali M, Abi Jaoude J, Tfayli A, et al. Post-mastectomy radiation therapy in breast cancer patients with 1–3 positive lymph nodes: No one size fits all. Crit Rev Oncol Hematol, 2020, 147: 102880.
3. 邱鹏飞, 王永胜. 乳腺癌内乳淋巴结精准分期与个体化治疗. 中国肿瘤外科杂志, 2020, 12(4): 306-310, 315.
4. Andersson Y, Bergkvist L, Frisell J, et al. Long-term breast cancer survival in relation to the metastatic tumor burden in axillary lymph nodes. Breast Cancer Res Treat, 2018, 171(2): 359-369.
5. Wu YY, Peck K, Chang YL, et al. SCUBE3 is an endogenous TGF-β receptor ligand and regulates the epithelial-mesenchymal transition in lung cancer. Oncogene, 2011, 30(34): 3682-3693.
6. Liu X, Wang LG, Zhang LC, et al. Molecular cloning, tissue expression pattern, and copy number variation of porcine SCUBE3. Genet Mol Res, 2016, 15(1): gmr7010.
7. Huo Q, He X, Li Z, et al. SCUBE3 serves as an independent poor prognostic factor in breast cancer. Cancer Cell Int, 2021, 21(1): 268.
8. 孔祥泉, 曾毅, 王立峰, 等. 乳腺癌组织中 SCUBE2 表达与临床病理特征的相关性研究. 慢性病学杂志, 2016, 17(8): 845-849.
9. Torabi B, Flashner S, Beishline K, et al. Caspase cleavage of transcription factor Sp1 enhances apoptosis. Apoptosis, 2018, 23(1): 65-78.
10. Zhang KF, Wang J, Guo J, et al. Metformin enhances radiosensitivity in hepatocellular carcinoma by inhibition of specificity protein 1 and epithelial-to-mesenchymal transition. J Cancer Res Ther, 2019, 15(7): 1603-1610.
11. 史晓宇, 张敬, 孟玮, 等. 转录因子 Sp1 和存活素在乳腺癌中的表达及相关性研究. 实用肿瘤学杂志, 2017, 31(2): 107-111.
12. 刘裔莎, 魏兵, 杨雯娟, 等. 美国癌症联合会乳腺癌分期(第七版)简介. 中华病理学杂志, 2010, 39(11): 787-790.
13. Bliss SA, Paul S, Pobiarzyn PW, et al. Evaluation of a developmental hierarchy for breast cancer cells to assess risk-based patient selection for targeted treatment. Sci Rep, 2018, 8(1): 367.
14. 卢小冬. 长链非编码 RNA 牛磺酸调节基因 1 和 miR-132 的表达与乳腺癌预后的关系. 中华普通外科学文献(电子版), 2020, 14(1): 5-9.
15. Said NM. Three gold indicators for breast cancer prognosis: a case-control study with ROC analysis for novel ratios related to CBC with (ALP and LDH). Mol Biol Rep, 2019, 46(2): 2013-2027.
16. Su F, Geng J, Li X, et al. SP1 promotes tumor angiogenesis and invasion by activating VEGF expression in an acquired trastuzumab-resistant ovarian cancer model. Oncol Rep, 2017, 38(5): 2677-2684.
17. Bolayır HA, Güneş H, Kıvrak T, et al. The role of SCUBE1 in the pathogenesis of no-reflow phenomenon presenting with ST segment elevation myocardial infarction. Anatol J Cardiol, 2017, 18(2): 122-127.
18. Yang X, Hu J, Shi C, et al. Activation of TGF-β1 pathway by SCUBE3 regulates TWIST1 expression and promotes breast cancer progression. Cancer Biother Radiopharm, 2020, 35(2): 120-128.
19. 李俊, 李国庆. 新型分泌型蛋白 SCUBE1 在急性冠脉综合征中促进无复流的研究进展. 新疆医学, 2018, 48(1): 91-93.
20. Chen JH, Kuo KT, Bamodu OA, et al. Upregulated SCUBE2 expression in breast cancer stem cells enhances triple negative breast cancer aggression through modulation of Notch signaling and epithelial-to-mesenchymal transition. Exp Cell Res, 2018, 370(2): 444-453.
21. Monteleone E, Orecchia V, Corrieri P, et al. SP1 and STAT3 functionally synergize to induce the RhoU small GTPase and a subclass of non-canonical WNT responsive genes correlating with poor prognosis in breast cancer. Cancers (Basel), 2019, 11(1): 101.
22. 韩亮, 张丽荣, 赵峰. 转录因子特异性蛋白 1 对三阴乳腺癌 HCC1806 细胞增殖凋亡的影响及其机制. 中华实验外科杂志, 2020, 37(7): 1201-1204.
23. Lee YJ, Kim WI, Kim SY, et al. Flavonoid morin inhibits proliferation and induces apoptosis of melanoma cells by regulating reactive oxygen species, Sp1 and Mcl-1. Arch Pharm Res, 2019, 42(6): 531-542.
24. 黎三艳, 郑眉嵩, 陈余鹏, 等. 孕激素抗体 EP2、SP2、1E2、16 在非特殊型浸润性乳腺癌的表达差异. 第三军医大学学报, 2020, 42(10): 1042-1046.
25. Zhang S, Huang P, Dai H, et al. Timeless regulates sphingolipid metabolism and tumor cell growth through Sp1/ACER2/S1P axis in ER-positive breast cancer. Cell Death Dis, 2020, 11(10): 892.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Relations between SCUBE3 or SP1 expression and clinicopathologic characteristics and prognosis of patients with breast cancer

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