Correlation between stromal interaction molecule 1 and tumor malignant degree or lymph node metastasis in patients with gastric cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

MA Bo ¹ ,  JIANG Huaiwu ^1,2 , XU Liang ¹ , XIAO Guo ² , YANG Siyu ³

1. Department of Gastrointestinal Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P. R. China;
2. Department of Gastrointestinal Surgery, The Sichuan Mianyang 404 Hospital, Mianyang, Sichuan 621000, P. R. China;
3. Department of Pathology, The Sichuan Mianyang 404 Hospital, Mianyang, Sichuan 621000, P. R. China;

Corresponding?author：

JIANG Huaiwu, Email: jhuaiwu@163.com

Keywords：

gastric cancer; stromal interaction molecule 1; lymph node metastasis; immunohistochemistry method

DOI：

10.7507/1007-9424.202107031

Video：

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Objective To investigate the correlation between expression of stromal interaction molecule 1 (STIM1) and tumor malignant degree or lymph node metastasis in patients with gastric cancer. Methods A total of 83 patients with gastric cancer treated in the Affiliated Hospital of Southwest Medical University and Sichuan Mianyang 404 Hospital from October 2018 to April 2021 were collected. The expression of STIM1 protein in the gastric cancer tissues and the corresponding adjacent normal gastric tissues was detected by immunohistochemistry method. Meanwhile the correlation between the expression of STIM1 protein and clinicopathologic features or postoperative lymph node status of the patients with gastric cancer was analyzed. Results The positive rate of STIM1 protein expression in the gastric cancer tissues was 95.2% (79/83), including 62 (74.7%) patients with high expression (STIM1 scoring 5–7) and 21 (25.3%) patients with low expression (STIM1 scoring 2–4), which in the corresponding adjacent normal gastric tissues was 41.0% (34/83), the difference was statistically significant (χ²=58.078, P<0.001). The expression of STIM1 protein was not related to gender, age, and tumor size of the patients with gastric cancer (P>0.05), while the proportions of the patients with high expression of STIM1 protein in the gastric cancer patients with low/undifferentiated tumor, T3+T4 of infiltration depth, TNM stage Ⅲ, and lymph node metastasis were higher than those with high/medium differentiation (χ²=11.052, P=0.001), T1+T2 of infiltration depth (χ²=24.720, P<0.001), TNM stage Ⅰ+Ⅱ (χ²=9.980, P=0.002), and non-lymph node metastasis (χ²=6.097, P=0.014). The expression intensity of STIM1 protein was positively correlated with the number of lymph node metastasis (r=0.552, Z=–3.098, P=0.002) and the rate of lymph node metastasis (r=0.561, Z=–6.387, P<0.001). Conclusions Positive rate of STIM1 protein expression in gastric cancer tissues is relatively high. STIM1 protein expression in gastric cancer tissue is closely related to tumor malignancy and lymph node metastasis, so it might play an important role in progression of gastric cancer.

Citation： MA Bo, JIANG Huaiwu, XU Liang, XIAO Guo, YANG Siyu. Correlation between stromal interaction molecule 1 and tumor malignant degree or lymph node metastasis in patients with gastric cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2022, 29(4): 465-469. doi: 10.7507/1007-9424.202107031 Copy

1.	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
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.	Sitarz R, Skierucha M, Mielko J, et al. Gastric cancer: epidemiology, prevention, classification, and treatment. Cancer Manag Res, 2018, 10: 239-248.
4.	國家衛生健康委員會. 胃癌診療規范(2018年版). 中華消化病與影像雜志(電子版), 2019, 9(3): 118-144.
5.	陳正偉, 何慶泗. 淋巴結切除數目對不同分期胃癌預后的影響. 濟南: 山東大學, 2021.
6.	徐金眉, 劉衛華. STIM1在胃癌中的表達及功能研究. 成都: 成都醫學院, 2015.
7.	胡祥, 張馳. 第15版日本《胃癌處理規約》拔萃. 中國實用外科雜志, 2018, 38(5): 520-528.
8.	何振, 李鵬, 張澍田. 消化道早癌內鏡診治進展. 浙江醫學, 2016, 38(6): 377-378, 388.
9.	喬樂樂, 王公平, 周博, 等. 胃癌患者術前CRP/Alb比與淋巴結轉移相關性的研究. 中國腫瘤臨床, 2017, 44(5): 210-213.
10.	閔叢叢. 胃癌淋巴結轉移分子標志物的研究進展. 中國微創外科雜志, 2018, 18(1): 68-71.
11.	Sabbioni S, Barbanti-Brodano G, Croce CM, et al. GOK: a gene at 11p15 involved in rhabdomyosarcoma and rhabdoid tumor development. Cancer Res, 1997, 57(20): 4493-4497.
12.	Woo JS, Srikanth S, Gwack Y. Modulation of Orai1 and STIM1 by cellular factors//Kozak JA, Putney JW Jr, editors. Calcium entry channels in non-excitable cells. Boca Raton (FL): CRC Press/Taylor & Francis, 2018.
13.	Choi S, Maleth J, Jha A, et al. The TRPCs-STIM1-Orai interaction. Handb Exp Pharmacol, 2014, 223: 1035-1054.
14.	張舒, 牟雯君, 陳思, 等. STIM1在前列腺癌增殖、凋亡及腫瘤微環境中的作用. 中國生物化學與分子生物學會醫學生物化學與分子生物學分會、中國生物化學與分子生物學會臨床應用生物化學與分子生物學分會. 第七屆全國醫學生物化學與分子生物學和第四屆全國臨床應用生物化學與分子生物學聯合學術研討會暨醫學生化分會會員代表大會論文集. 中國生物化學與分子生物學會醫學生物化學與分子生物學分會、中國生物化學與分子生物學會臨床應用生物化學與分子生物學分會: 中國生物化學與分子生物學會, 2011: 235.
15.	Yang Y, Jiang Z, Wang B, et al. Expression of STIM1 is associated with tumor aggressiveness and poor prognosis in breast cancer. Pathol Res Pract, 2017, 213(9): 1043-1047.
16.	Yang S, Zhang JJ, Huang XY. Orai1 and STIM1 are critical for breast tumor cell migration and metastasis. Cancer Cell, 2009, 15(2): 124-134.
17.	Chen YF, Chiu WT, Chen YT, et al. Calcium store sensor stromal-interaction molecule 1-dependent signaling plays an important role in cervical cancer growth, migration, and angiogenesis. Proc Natl Acad Sci USA, 2011, 108(37): 15225-15230.
18.	Sun Y, Cui X, Wang J, et al. Stromal interaction molecule 1 (STIM1) silencing inhibits tumor growth and promotes cell cycle arrest and apoptosis in hypopharyngeal carcinoma. Med Oncol, 2015, 32(5): 150. doi: 10.1007/s12032-015-0608-9.
19.	Ge C, Zeng B, Li R, et al. Knockdown of STIM1 expression inhibits non-small-cell lung cancer cell proliferation in vitro and in nude mouse xenografts. Bioengineered, 2019, 10(1): 425-436.
20.	Zhao H, Yan G, Zheng L, et al. STIM1 is a metabolic checkpoint regulating the invasion and metastasis of hepatocellular carcinoma. Theranostics, 2020, 10(14): 6483-6499.
21.	Li P, Bian XY, Chen Q, et al. Blocking of stromal interaction molecule 1 expression influence cell proliferation and promote cell apoptosis in vitro and inhibit tumor growth in vivo in head and neck squamous cell carcinoma. PLoS One, 2017, 12(5): e0177484. doi: 10.1371/journal.pone.0177484.
22.	宋來小, 崔曉波. STIM1基因與頭頸部腫瘤關系的研究進展. 內蒙古醫學雜志, 2018, 50(3): 291-293.
23.	Xu JM, Zhou Y, Gao L, et al. Stromal interaction molecule 1 plays an important role in gastric cancer progression. Oncol Rep, 2016, 35(6): 3496-3504.
24.	Li J, Sukumar P, Milligan CJ, et al. Interactions, functions, and independence of plasma membrane STIM1 and TRPC1 in vascular smooth muscle cells. Circ Res, 2008, 103(8): e97-e104. doi: 10.1161/CIRCRESAHA.108.182931.
25.	Liu B, Yu HH, Ye HL, et al. Effects of stromal interacting molecule 1 gene silencing by short hairpin RNA on the biological behavior of human gastric cancer cells. Mol Med Rep, 2015, 12(2): 3047-3054.
26.	張明芳, 王丹, 王情, 等. 動脈平滑肌細胞 STIM1過表達上調Akt/mTOR 通路并促進細胞增殖. 中國藥理學通報, 2016, 32(1): 37-42.
27.	Huang Z, Li P, Wu L, et al. Hsa_circ_0029589 knockdown inhibits the proliferation, migration and invasion of vascular smooth muscle cells via regulating miR-214-3p and STIM1. Life Sci, 2020, 259: 118251. doi: 10.1016/j.lfs.2020.118251.
28.	Xia J, Wang H, Huang H, et al. Elevated Orai1 and STIM1 expressions upregulate MACC1 expression to promote tumor cell proliferation, metabolism, migration, and invasion in human gastric cancer. Cancer Lett, 2016, 381(1): 31-40.
29.	Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2007. CA Cancer J Clin, 2007, 57(1): 43-66.
30.	李彩蘋, 房太勇. CDX2蛋白, P53蛋白和Ki67抗原在胃癌組織中的表達及意義. 福州: 福建醫科大學, 2014.
31.	葉玉偉, 周永寧. 高發區胃癌防控策略及前瞻性隊列建設研究. 蘭州: 蘭州大學, 2017.
32.	Wang JJ, Lei KF, Han F. Tumor microenvironment: recent advances in various cancer treatments. Eur Rev Med Pharmacol Sci, 2018, 22(12): 3855-3864.
33.	Vashisht A, Trebak M, Motiani RK. STIM and Orai proteins as novel targets for cancer therapy. A review in the theme: cell and molecular processes in cancer metastasis. Am J Physiol Cell Physiol, 2015, 309(7): C457-C469. doi: 10.1152/ajpcell.00064.2015.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
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. Sitarz R, Skierucha M, Mielko J, et al. Gastric cancer: epidemiology, prevention, classification, and treatment. Cancer Manag Res, 2018, 10: 239-248.
4. 國家衛生健康委員會. 胃癌診療規范(2018年版). 中華消化病與影像雜志(電子版), 2019, 9(3): 118-144.
5. 陳正偉, 何慶泗. 淋巴結切除數目對不同分期胃癌預后的影響. 濟南: 山東大學, 2021.
6. 徐金眉, 劉衛華. STIM1在胃癌中的表達及功能研究. 成都: 成都醫學院, 2015.
7. 胡祥, 張馳. 第15版日本《胃癌處理規約》拔萃. 中國實用外科雜志, 2018, 38(5): 520-528.
8. 何振, 李鵬, 張澍田. 消化道早癌內鏡診治進展. 浙江醫學, 2016, 38(6): 377-378, 388.
9. 喬樂樂, 王公平, 周博, 等. 胃癌患者術前CRP/Alb比與淋巴結轉移相關性的研究. 中國腫瘤臨床, 2017, 44(5): 210-213.
10. 閔叢叢. 胃癌淋巴結轉移分子標志物的研究進展. 中國微創外科雜志, 2018, 18(1): 68-71.
11. Sabbioni S, Barbanti-Brodano G, Croce CM, et al. GOK: a gene at 11p15 involved in rhabdomyosarcoma and rhabdoid tumor development. Cancer Res, 1997, 57(20): 4493-4497.
12. Woo JS, Srikanth S, Gwack Y. Modulation of Orai1 and STIM1 by cellular factors//Kozak JA, Putney JW Jr, editors. Calcium entry channels in non-excitable cells. Boca Raton (FL): CRC Press/Taylor & Francis, 2018.
13. Choi S, Maleth J, Jha A, et al. The TRPCs-STIM1-Orai interaction. Handb Exp Pharmacol, 2014, 223: 1035-1054.
14. 張舒, 牟雯君, 陳思, 等. STIM1在前列腺癌增殖、凋亡及腫瘤微環境中的作用. 中國生物化學與分子生物學會醫學生物化學與分子生物學分會、中國生物化學與分子生物學會臨床應用生物化學與分子生物學分會. 第七屆全國醫學生物化學與分子生物學和第四屆全國臨床應用生物化學與分子生物學聯合學術研討會暨醫學生化分會會員代表大會論文集. 中國生物化學與分子生物學會醫學生物化學與分子生物學分會、中國生物化學與分子生物學會臨床應用生物化學與分子生物學分會: 中國生物化學與分子生物學會, 2011: 235.
15. Yang Y, Jiang Z, Wang B, et al. Expression of STIM1 is associated with tumor aggressiveness and poor prognosis in breast cancer. Pathol Res Pract, 2017, 213(9): 1043-1047.
16. Yang S, Zhang JJ, Huang XY. Orai1 and STIM1 are critical for breast tumor cell migration and metastasis. Cancer Cell, 2009, 15(2): 124-134.
17. Chen YF, Chiu WT, Chen YT, et al. Calcium store sensor stromal-interaction molecule 1-dependent signaling plays an important role in cervical cancer growth, migration, and angiogenesis. Proc Natl Acad Sci USA, 2011, 108(37): 15225-15230.
18. Sun Y, Cui X, Wang J, et al. Stromal interaction molecule 1 (STIM1) silencing inhibits tumor growth and promotes cell cycle arrest and apoptosis in hypopharyngeal carcinoma. Med Oncol, 2015, 32(5): 150. doi: 10.1007/s12032-015-0608-9.
19. Ge C, Zeng B, Li R, et al. Knockdown of STIM1 expression inhibits non-small-cell lung cancer cell proliferation in vitro and in nude mouse xenografts. Bioengineered, 2019, 10(1): 425-436.
20. Zhao H, Yan G, Zheng L, et al. STIM1 is a metabolic checkpoint regulating the invasion and metastasis of hepatocellular carcinoma. Theranostics, 2020, 10(14): 6483-6499.
21. Li P, Bian XY, Chen Q, et al. Blocking of stromal interaction molecule 1 expression influence cell proliferation and promote cell apoptosis in vitro and inhibit tumor growth in vivo in head and neck squamous cell carcinoma. PLoS One, 2017, 12(5): e0177484. doi: 10.1371/journal.pone.0177484.
22. 宋來小, 崔曉波. STIM1基因與頭頸部腫瘤關系的研究進展. 內蒙古醫學雜志, 2018, 50(3): 291-293.
23. Xu JM, Zhou Y, Gao L, et al. Stromal interaction molecule 1 plays an important role in gastric cancer progression. Oncol Rep, 2016, 35(6): 3496-3504.
24. Li J, Sukumar P, Milligan CJ, et al. Interactions, functions, and independence of plasma membrane STIM1 and TRPC1 in vascular smooth muscle cells. Circ Res, 2008, 103(8): e97-e104. doi: 10.1161/CIRCRESAHA.108.182931.
25. Liu B, Yu HH, Ye HL, et al. Effects of stromal interacting molecule 1 gene silencing by short hairpin RNA on the biological behavior of human gastric cancer cells. Mol Med Rep, 2015, 12(2): 3047-3054.
26. 張明芳, 王丹, 王情, 等. 動脈平滑肌細胞 STIM1過表達上調Akt/mTOR 通路并促進細胞增殖. 中國藥理學通報, 2016, 32(1): 37-42.
27. Huang Z, Li P, Wu L, et al. Hsa_circ_0029589 knockdown inhibits the proliferation, migration and invasion of vascular smooth muscle cells via regulating miR-214-3p and STIM1. Life Sci, 2020, 259: 118251. doi: 10.1016/j.lfs.2020.118251.
28. Xia J, Wang H, Huang H, et al. Elevated Orai1 and STIM1 expressions upregulate MACC1 expression to promote tumor cell proliferation, metabolism, migration, and invasion in human gastric cancer. Cancer Lett, 2016, 381(1): 31-40.
29. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2007. CA Cancer J Clin, 2007, 57(1): 43-66.
30. 李彩蘋, 房太勇. CDX2蛋白, P53蛋白和Ki67抗原在胃癌組織中的表達及意義. 福州: 福建醫科大學, 2014.
31. 葉玉偉, 周永寧. 高發區胃癌防控策略及前瞻性隊列建設研究. 蘭州: 蘭州大學, 2017.
32. Wang JJ, Lei KF, Han F. Tumor microenvironment: recent advances in various cancer treatments. Eur Rev Med Pharmacol Sci, 2018, 22(12): 3855-3864.
33. Vashisht A, Trebak M, Motiani RK. STIM and Orai proteins as novel targets for cancer therapy. A review in the theme: cell and molecular processes in cancer metastasis. Am J Physiol Cell Physiol, 2015, 309(7): C457-C469. doi: 10.1152/ajpcell.00064.2015.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Correlation between stromal interaction molecule 1 and tumor malignant degree or lymph node metastasis in patients with gastric cancer

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