Expression of CPNE1 in gastric cancer tissues and its relationship with prognosis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHOU Qian ^1,2,3 , CHEN Peng ² , GAO Xiaoxin ² , DU Chengzhou ² ,  LI Hongtao ^1,2

1. Second Clinical Medical College of Lanzhou University, Lanzhou 730030, P. R. China;
2. Department of General Surgery, The 940th Hospital of Joint Logistics Support Force of the People’s Liberation Army, Lanzhou 730050, P. R. China;
3. Key Laboratory of Stem Cells and Gene Drugs of Gansu Provincial, Lanzhou 730000, P. R. China;

Corresponding author：

LI Hongtao, Email: lihongtao528@163.com

Keywords：

gastric cancer; copine 1; clinicopathological characteristic; prognosis

DOI：

10.7507/1007-9424.202408038

Video：

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Objective To investigate the expression of calcium-dependent phospholipid binding protein 1 (CPNE1) in gastric cancer (GC) and the correlation with prognosis. Methods The clinicopathological data of 121 patients who underwent radical gastrectomy in the Department of General Surgery, The 940th Hospital of Joint Logistics Support Force of the People’s Liberation Army from March 2017 to December 2018 were retrospectively collected. The expression of CPNE1 in gastric cancer tissues was detected by immunohistochemical (IHC) staining, and its relationship with prognosis was analyzed. Gastric cancer tissue samples and adjacent tissue samples from 16 patients in the same time were prospectively collected, and the mRNA and protein expressions of CPNE1 were detected by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blotting (WB), respectively. Multivariate Cox proportional hazard regression model was used to analyze the prognostic factors of gastric cancer patients. Results IHC staining results showed that CPNE1 was mainly expressed in the cell membrane and cytoplasm of gastric epithelial cells, and the color showed different degrees of brown. Among the 121 patients, 70 (57.9%) had high CPNE1 expression and 51 (42.1%) had low CPNE1 expression. The RT-qPCR and WB results of 16 pairs of fresh tissue specimens showed that the expression levels of CPNE1 mRNA and protein in gastric cancer tissues were higher than those in adjacent tissues (gastric cancer tissue vs. adjacent tissue: CPNE1 mRNA 1.451 vs. 1.100, P=0.048; CPNE1, 0.995 vs. 0.521, P=0.001). Multivariate Cox proportional hazards regression analysis showed that high expression of CPNE1 [HR=1.923, 95%CI (1.124, 3.290), P=0.017] was risk factors affecting the prognosis of patients with gastric cancer. Conclusion CPNE1 is highly expressed in gastric cancer tissues and is associated with a poor prognosis in patients, and it may be a potential tumor biomarker.

1.	Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin, 2024, 74(1): 12-49.
2.	姚一菲, 孙可欣, 郑荣寿. 《2022全球癌症统计报告》解读: 中国与全球对比. 中国普外基础与临床杂志, 2024, 31(7): 769-780.
3.	李茁钰, 刘凯, 张维汉, 等. 全球及中国胃癌的流行病学特点及趋势: 2018–2022《全球癌症统计报告》解读. 中国普外基础与临床杂志, 2024, 31(10): 1236-1245.
4.	刘珊山, 何昱静, 郑英, 等. 2015年—2018年甘肃省恶性肿瘤发病和死亡情况及变化趋势分析. 肿瘤, 2024, 44(2): 169-179.
5.	朱奕潼, 袁浩冉, 丁高恒, 等. 2018年甘肃省肿瘤登记地区胃癌流行特征及2010-2018年变化趋势. 中国肿瘤, 2022, 31(12): 992-1000.
6.	蒲柯. 武威队列饮食模式与胃癌、癌前病变及幽门螺旋杆菌感染相关性研究. 兰州: 兰州大学, 2020.
7.	Zhou H, He Y, Huang Y, et al. Comprehensive analysis of prognostic value, immune implication and biological function of CPNE1 in clear cell renal cell carcinoma. Front Cell Dev Biol, 2023, 11: 1157269.
8.	Tang H, Pang P, Qin Z, et al. The CPNE family and their role in cancers. Front Genet, 2021, 12: 689097.
9.	张晓红, 李凡, 贝颂华, 等. CPNE家族在胃癌中的表达水平及其与患者预后的关系. 国际消化病杂志, 2020, 40(6): 377-383.
10.	Hofmann M, Stoss O, Shi D, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology, 2008, 52(7): 797-805.
11.	Cao Y, Liang H, Zhang F, et al. Prohibitin overexpression predicts poor prognosis and promotes cell proliferation and invasion through ERK pathway activation in gallbladder cancer. J Exp Clin Cancer Res, 2016, 35: 68.
12.	焦淑成, 王恒, 杜彦峥. 血清CEA和CA199表达水平评估胃癌病情的应用价值. 国际检验医学杂志, 2014(6): 661-662,666.
13.	Yoo JC, Park N, Choi HY, et al. JAB1 regulates CPNE1-related differentiation via direct binding to CPNE1 in HiB5 hippocampal progenitor cells. Biochem Biophys Res Commun, 2018, 497(1): 424-429.
14.	Choi HY, Park N, Lee B, et al. CPNE1-mediated neuronal differentiation can be inhibited by HAX1 expression in HiB5 cells. Biochem Biophys Res Commun, 2020, 533(3): 319-324.
15.	Yang W, Ng P, Zhao M, et al. Promoter-sharing by different genes in human genome–CPNE1 and RBM12 gene pair as an example. BMC Genomics, 2008, 9(1): 456.
16.	Ilacqua AN, Price JE, Graham BN, et al. Cyclic AMP signaling in Dictyostelium promotes the translocation of the copine family of calcium-binding proteins to the plasma membrane. BMC Cell Biol, 2018, 19(1): 13.
17.	El-Huneidi W, Anjum S, Mohammed AK, et al. Copine 3 “CPNE3” is a novel regulator for insulin secretion and glucose uptake in pancreatic β-cells. Sci Rep, 2021, 11(1): 20692.
18.	Yu T, Huang C, Lai C, et al. Copine 7 promotes colorectal cancer proliferation through PKM2 interaction and MAPK signaling pathway. Front Oncol, 2023, 13: 1166444.
19.	Park N, Yoo JC, Ryu J, et al. Copine1 enhances neuronal differentiation of the hippocampal progenitor HiB5 cells. Mol Cells, 2012, 34(6): 549-554.
20.	Liu S, Tang H, Zhu J, et al. High expression of Copine 1 promotes cell growth and metastasis in human lung adenocarcinoma. Int J Oncol, 2018, 53(6): 2369-2378.
21.	Paricharttanakul NM, Saharat K, Chokchaichamnankit D, et al. Unveiling a novel biomarker panel for diagnosis and classification of well-differentiated thyroid carcinomas. Oncol Rep, 2016, 35(4): 2286-2296.
22.	Su J, Huang Y, Wang Y, et al. CPNE1 is a potential prognostic biomarker, associated with immune infiltrates and promotes progression of hepatocellular carcinoma. Cancer Cell Int, 2022, 22(1): 67.
23.	Jiang Z, Jiang J, Zhao B, et al. CPNE1 silencing inhibits the proliferation, invasion and migration of human osteosarcoma cells. Oncol Rep, 2018, 39(2): 643-650.
24.	Shao Z, Ma X, Zhang Y, et al. CPNE1 predicts poor prognosis and promotes tumorigenesis and radioresistance via the AKT singling pathway in triple-negative breast cancer. Mol Carcinog, 2020, 59(5): 533-544.
25.	Cao J, Cao R, Liu Y, et al. CPNE1 mediates glycolysis and metastasis of breast cancer through activation of PI3K/AKT/HIF-1α signaling. Pathol Res Pract, 2023, 248: 154634.
26.	Sheng B, Zhao B, Dong Y, et al. Copine 1 predicts poor clinical outcomes by promoting M2 macrophage activation in ovarian cancer. Carcinogenesis. 2023, 44(10-11): 748-759.
27.	Wang A, Yang W, Li Y, et al. CPNE1 promotes non-small cell lung cancer progression by interacting with RACK1 via the MET signaling pathway. Cell Commun Signal, 2022, 20(1): 16.
28.	Wang Y, Pan S, He X, et al. CPNE1 enhances colorectal cancer cell growth, glycolysis, and drug resistance through regulating the AKT-GLUT1/HK2 pathway. Onco Targets Ther, 2021, 14: 699-710.
29.	Jang J, Lee S, Ko KP, et al. Association between body mass index and risk of gastric cancer by anatomic and histologic subtypes in over 500, 000 East and Southeast Asian cohort participants. Cancer Epidemiol Biomarkers Prev, 2022, 31(9): 1727-1734.

1. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin, 2024, 74(1): 12-49.
2. 姚一菲, 孙可欣, 郑荣寿. 《2022全球癌症统计报告》解读: 中国与全球对比. 中国普外基础与临床杂志, 2024, 31(7): 769-780.
3. 李茁钰, 刘凯, 张维汉, 等. 全球及中国胃癌的流行病学特点及趋势: 2018–2022《全球癌症统计报告》解读. 中国普外基础与临床杂志, 2024, 31(10): 1236-1245.
4. 刘珊山, 何昱静, 郑英, 等. 2015年—2018年甘肃省恶性肿瘤发病和死亡情况及变化趋势分析. 肿瘤, 2024, 44(2): 169-179.
5. 朱奕潼, 袁浩冉, 丁高恒, 等. 2018年甘肃省肿瘤登记地区胃癌流行特征及2010-2018年变化趋势. 中国肿瘤, 2022, 31(12): 992-1000.
6. 蒲柯. 武威队列饮食模式与胃癌、癌前病变及幽门螺旋杆菌感染相关性研究. 兰州: 兰州大学, 2020.
7. Zhou H, He Y, Huang Y, et al. Comprehensive analysis of prognostic value, immune implication and biological function of CPNE1 in clear cell renal cell carcinoma. Front Cell Dev Biol, 2023, 11: 1157269.
8. Tang H, Pang P, Qin Z, et al. The CPNE family and their role in cancers. Front Genet, 2021, 12: 689097.
9. 张晓红, 李凡, 贝颂华, 等. CPNE家族在胃癌中的表达水平及其与患者预后的关系. 国际消化病杂志, 2020, 40(6): 377-383.
10. Hofmann M, Stoss O, Shi D, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology, 2008, 52(7): 797-805.
11. Cao Y, Liang H, Zhang F, et al. Prohibitin overexpression predicts poor prognosis and promotes cell proliferation and invasion through ERK pathway activation in gallbladder cancer. J Exp Clin Cancer Res, 2016, 35: 68.
12. 焦淑成, 王恒, 杜彦峥. 血清CEA和CA199表达水平评估胃癌病情的应用价值. 国际检验医学杂志, 2014(6): 661-662,666.
13. Yoo JC, Park N, Choi HY, et al. JAB1 regulates CPNE1-related differentiation via direct binding to CPNE1 in HiB5 hippocampal progenitor cells. Biochem Biophys Res Commun, 2018, 497(1): 424-429.
14. Choi HY, Park N, Lee B, et al. CPNE1-mediated neuronal differentiation can be inhibited by HAX1 expression in HiB5 cells. Biochem Biophys Res Commun, 2020, 533(3): 319-324.
15. Yang W, Ng P, Zhao M, et al. Promoter-sharing by different genes in human genome–CPNE1 and RBM12 gene pair as an example. BMC Genomics, 2008, 9(1): 456.
16. Ilacqua AN, Price JE, Graham BN, et al. Cyclic AMP signaling in Dictyostelium promotes the translocation of the copine family of calcium-binding proteins to the plasma membrane. BMC Cell Biol, 2018, 19(1): 13.
17. El-Huneidi W, Anjum S, Mohammed AK, et al. Copine 3 “CPNE3” is a novel regulator for insulin secretion and glucose uptake in pancreatic β-cells. Sci Rep, 2021, 11(1): 20692.
18. Yu T, Huang C, Lai C, et al. Copine 7 promotes colorectal cancer proliferation through PKM2 interaction and MAPK signaling pathway. Front Oncol, 2023, 13: 1166444.
19. Park N, Yoo JC, Ryu J, et al. Copine1 enhances neuronal differentiation of the hippocampal progenitor HiB5 cells. Mol Cells, 2012, 34(6): 549-554.
20. Liu S, Tang H, Zhu J, et al. High expression of Copine 1 promotes cell growth and metastasis in human lung adenocarcinoma. Int J Oncol, 2018, 53(6): 2369-2378.
21. Paricharttanakul NM, Saharat K, Chokchaichamnankit D, et al. Unveiling a novel biomarker panel for diagnosis and classification of well-differentiated thyroid carcinomas. Oncol Rep, 2016, 35(4): 2286-2296.
22. Su J, Huang Y, Wang Y, et al. CPNE1 is a potential prognostic biomarker, associated with immune infiltrates and promotes progression of hepatocellular carcinoma. Cancer Cell Int, 2022, 22(1): 67.
23. Jiang Z, Jiang J, Zhao B, et al. CPNE1 silencing inhibits the proliferation, invasion and migration of human osteosarcoma cells. Oncol Rep, 2018, 39(2): 643-650.
24. Shao Z, Ma X, Zhang Y, et al. CPNE1 predicts poor prognosis and promotes tumorigenesis and radioresistance via the AKT singling pathway in triple-negative breast cancer. Mol Carcinog, 2020, 59(5): 533-544.
25. Cao J, Cao R, Liu Y, et al. CPNE1 mediates glycolysis and metastasis of breast cancer through activation of PI3K/AKT/HIF-1α signaling. Pathol Res Pract, 2023, 248: 154634.
26. Sheng B, Zhao B, Dong Y, et al. Copine 1 predicts poor clinical outcomes by promoting M2 macrophage activation in ovarian cancer. Carcinogenesis. 2023, 44(10-11): 748-759.
27. Wang A, Yang W, Li Y, et al. CPNE1 promotes non-small cell lung cancer progression by interacting with RACK1 via the MET signaling pathway. Cell Commun Signal, 2022, 20(1): 16.
28. Wang Y, Pan S, He X, et al. CPNE1 enhances colorectal cancer cell growth, glycolysis, and drug resistance through regulating the AKT-GLUT1/HK2 pathway. Onco Targets Ther, 2021, 14: 699-710.
29. Jang J, Lee S, Ko KP, et al. Association between body mass index and risk of gastric cancer by anatomic and histologic subtypes in over 500, 000 East and Southeast Asian cohort participants. Cancer Epidemiol Biomarkers Prev, 2022, 31(9): 1727-1734.

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