The clinical significance of GSDMD and caspase<b>-</b>1 expressions in the invasive ductal breast carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Qian ,  ZHAO Haibin

Department of Pathology, The 904th Hospital of Joint Logistic Support Force of PLA, Wuxi, Jiangsu 214044, P. R. China;

Corresponding author：

ZHAO Haibin, Email: 552006953@qq.com

Keywords：

invasive ductal carcinoma of breast; gasdermin-D; caspase-1; prognosis

DOI：

10.7507/1007-9424.202108084

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To study the clinical significance of gasdermin-D（GSDMD) and caspase-1 expressions in the invasive ductal breast carcinoma. Methods Seventy-seven female patients with invasive ductal carcinoma of breast performed radical resection in the 904th Hospital of Joint Logistic Support Force of PLA from January 2015 to June 2016 were selected as the research object. The expressions of GSDMD and caspase-1 protein in cancer tissues and 20 adjacent tissues were detected by immunohistochemistry, and their correlation with clinicopathological features was analyzed. Kaplan-Meier analysis was used to draw the survival curve, and log-rank test was used for univariate survival analysis, and Cox proportional hazards regression analysis of prognostic factors in patients with breast invasive ductal carcinoma. Results The proportion of high expression of GSDMD and caspase-1 protein in adjacent tissues were significantly higher than those in breast cancer tissues (P<0.05). Univariate analysis results showed that the survival time of patients with invasive ductal carcinoma of breast were correlated with lymphatic metastasis, TNM staging, and the expression status of progesterone receptor, GSDMD, caspase-1 and Ki-67 (P<0.05). Multivariate analysis results showed that the low expression of GSDMD protein [HR=4.096, 95%CI (1.102, 15.216), P<0.05] and low expression of caspase-1 protein [HR=3.945, 95%CI (1.062, 14.652), P<0.05] were the independent risk factor that affect the survival rate of patients with invasive ductal carcinoma of breast. Conclusion The low expression of GSDMD and caspase-1 protein in invasive ductal carcinoma of breast are independent risk factors for postoperative survival.

Citation： WANG Qian, ZHAO Haibin. The clinical significance of GSDMD and caspase-1 expressions in the invasive ductal breast carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2022, 29(6): 768-773. doi: 10.7507/1007-9424.202108084 Copy

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2.	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
3.	刘广, 王永胜. 乳腺癌新辅助化疗后保乳手术研究进展. 中国普外基础与临床杂志, 2010, 17(12): 1249-1252.
4.	Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
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6.	Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet, 2014, 384(9938): 164-172.
7.	Broz P. Immunology: caspase target drives pyroptosis. Nature, 2015, 526(7575): 642-643.
8.	Wang WJ, Chen D, Jiang MZ, et al. Downregulation of gasdermin D promotes gastric cancer proliferation by regulating cell cycle-related proteins. J Dig Dis, 2018, 19(2): 74-83.
9.	Ma Y, Chen Y, Lin C, et al. Biological functions and clinical significance of the newly identified long non-coding RNA RP1-85F18. 6 in colorectal cancer. Oncol Rep, 2018, 40(5): 2648-2658.
10.	Gao J, Qiu X, Xi G, et al. Downregulation of GSDMD attenuates tumor proliferation via the intrinsic mitochondrial apoptotic pathway and inhibition of EGFR/Akt signaling and predicts a good prognosis in non-small cell lung cancer. Oncol Rep, 2018, 40(4): 1971-1984.
11.	Peng J, Jiang H, Guo J, et al. CD147 expression is associated with tumor proliferation in bladder cancer via GSDMD. Biomed Res Int, 2020, 2020: 7638975. doi: 10.1155/2020/7638975.
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13.	Gaidt MM, Hornung V. Pore formation by GSDMD is the effector mechanism of pyroptosis. EMBO J, 2016, 35(20): 2167-2169.
14.	Xia X, Wang X, Cheng Z, et al. The role of pyroptosis in cancer: pro-cancer or pro-“host”? Cell Death Dis, 2019, 10(9): 650. doi: 10.1038/s41419-019-1883-8.
15.	Liu J, Gao L, Zhu X, et al. Gasdermin D is a novel prognostic biomarker and relates to TMZ response in glioblastoma. Cancers (Basel), 2021, 13(22): 5620. doi: 10.3390/cancers13225620.
16.	Martinon F, Tschopp J. Inflammatory caspases and inflammasomes: master switches of inflammation. Cell Death Differ, 2007, 14(1): 10-22.
17.	Molla MD, Akalu Y, Geto Z, et al. Role of caspase-1 in the pathogenesis of inflammatory-associated chronic noncommunicable diseases. J Inflamm Res, 2020, 13: 749-764.
18.	Domblides C, Soubeyran I, Lartigue L, et al. Prognostic role of inflammasome components in human colorectal cancer. Cancers (Basel). 2020, 12(12): 3500. doi: 10.3390/cancers12123500.
19.	Winter RN, Kramer A, Borkowski A, et al. Loss of caspase-1 and caspase-3 protein expression in human prostate cancer. Cancer Res, 2001, 61(3): 1227-1232.
20.	Sun Y, Guo Y. Expression of caspase-1 in breast cancer tissues and its effects on cell proliferation, apoptosis and invasion. Oncol Lett, 2018, 15(5): 6431-6435.
21.	Tsuchiya K. Switching from apoptosis to pyroptosis: gasdermin-elicited inflammation and antitumor immunity. Int J Mol Sci, 2021, 22(1): 426. doi: 10.3390/ijms22010426.
22.	Wang K, Sun Q, Zhong X, et al. Structural mechanism for GSDMD targeting by autoprocessed caspases in pyroptosis. Cell, 2020, 180(5): 941-955.
23.	Yang Y, Liu PY, Bao W, et al. Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway. BMC Cancer, 2020, 20(1): 28. doi: 10.1186/s12885-019-6491-6.
24.	Yue E, Tuguzbaeva G, Chen X, et al. Anthocyanin is involved in the activation of pyroptosis in oral squamous cell carcinoma. Phytomedicine, 2019, 56: 286-294.

1. Li X, Zeng Z, Wang J, et al. MicroRNA-9 and breast cancer. Biomed Pharmacother, 2020, 122: 109687. doi: 10.1016/j.biopha.2019.109687.
2. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
3. 刘广, 王永胜. 乳腺癌新辅助化疗后保乳手术研究进展. 中国普外基础与临床杂志, 2010, 17(12): 1249-1252.
4. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
5. Malvezzi M, Bertuccio P, Rosso T, et al. European cancer mortality predictions for the year 2015: does lung cancer have the highest death rate in EU women? Ann Oncol, 2015, 26(4): 779-786.
6. Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet, 2014, 384(9938): 164-172.
7. Broz P. Immunology: caspase target drives pyroptosis. Nature, 2015, 526(7575): 642-643.
8. Wang WJ, Chen D, Jiang MZ, et al. Downregulation of gasdermin D promotes gastric cancer proliferation by regulating cell cycle-related proteins. J Dig Dis, 2018, 19(2): 74-83.
9. Ma Y, Chen Y, Lin C, et al. Biological functions and clinical significance of the newly identified long non-coding RNA RP1-85F18. 6 in colorectal cancer. Oncol Rep, 2018, 40(5): 2648-2658.
10. Gao J, Qiu X, Xi G, et al. Downregulation of GSDMD attenuates tumor proliferation via the intrinsic mitochondrial apoptotic pathway and inhibition of EGFR/Akt signaling and predicts a good prognosis in non-small cell lung cancer. Oncol Rep, 2018, 40(4): 1971-1984.
11. Peng J, Jiang H, Guo J, et al. CD147 expression is associated with tumor proliferation in bladder cancer via GSDMD. Biomed Res Int, 2020, 2020: 7638975. doi: 10.1155/2020/7638975.
12. Xue Y, Du HD, Tang D, et al. Correlation between the NLRP3 inflammasome and the prognosis of patients with LSCC. Front Oncol, 2019, 9: 588. doi: 10.3389/fonc.2019.00588.
13. Gaidt MM, Hornung V. Pore formation by GSDMD is the effector mechanism of pyroptosis. EMBO J, 2016, 35(20): 2167-2169.
14. Xia X, Wang X, Cheng Z, et al. The role of pyroptosis in cancer: pro-cancer or pro-“host”? Cell Death Dis, 2019, 10(9): 650. doi: 10.1038/s41419-019-1883-8.
15. Liu J, Gao L, Zhu X, et al. Gasdermin D is a novel prognostic biomarker and relates to TMZ response in glioblastoma. Cancers (Basel), 2021, 13(22): 5620. doi: 10.3390/cancers13225620.
16. Martinon F, Tschopp J. Inflammatory caspases and inflammasomes: master switches of inflammation. Cell Death Differ, 2007, 14(1): 10-22.
17. Molla MD, Akalu Y, Geto Z, et al. Role of caspase-1 in the pathogenesis of inflammatory-associated chronic noncommunicable diseases. J Inflamm Res, 2020, 13: 749-764.
18. Domblides C, Soubeyran I, Lartigue L, et al. Prognostic role of inflammasome components in human colorectal cancer. Cancers (Basel). 2020, 12(12): 3500. doi: 10.3390/cancers12123500.
19. Winter RN, Kramer A, Borkowski A, et al. Loss of caspase-1 and caspase-3 protein expression in human prostate cancer. Cancer Res, 2001, 61(3): 1227-1232.
20. Sun Y, Guo Y. Expression of caspase-1 in breast cancer tissues and its effects on cell proliferation, apoptosis and invasion. Oncol Lett, 2018, 15(5): 6431-6435.
21. Tsuchiya K. Switching from apoptosis to pyroptosis: gasdermin-elicited inflammation and antitumor immunity. Int J Mol Sci, 2021, 22(1): 426. doi: 10.3390/ijms22010426.
22. Wang K, Sun Q, Zhong X, et al. Structural mechanism for GSDMD targeting by autoprocessed caspases in pyroptosis. Cell, 2020, 180(5): 941-955.
23. Yang Y, Liu PY, Bao W, et al. Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway. BMC Cancer, 2020, 20(1): 28. doi: 10.1186/s12885-019-6491-6.
24. Yue E, Tuguzbaeva G, Chen X, et al. Anthocyanin is involved in the activation of pyroptosis in oral squamous cell carcinoma. Phytomedicine, 2019, 56: 286-294.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

The clinical significance of GSDMD and caspase-1 expressions in the invasive ductal breast carcinoma

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