Effect of calumenin on metastasis and invasion of gastric cancer and prognosis of patients

REN Zhixiang; LIU Jiajia; QIN Zhongyi; WANG Junjie; ZHENG Yiming; WANG Bin; QIAN Feng

doi:10.16016/j.2097-0927.202409151

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Effect of calumenin on metastasis and invasion of gastric cancer and prognosis of patients

Monographic Reports | 更新时间：2025-03-11

- Effect of calumenin on metastasis and invasion of gastric cancer and prognosis of patients
- Journal of Army Medical University Vol. 47, Issue 5, Pages: 435-442(2025)
- 作者机构：
  
  1.陆军军医大学（第三军医大学）第一附属医院普通外科，重庆
  2.陆军特色医学中心（第三军医大学大坪医院），消化内科消化系统肿瘤精准防治重庆市重点实验室，重庆
- 作者简介：
- 基金信息：
  
  the General Project of Natural Science Foundation of Chongqing(CSTB2022NSCQ-MSX0195;CSTC2021JCYJ-MSXMX1208)
- DOI：10.16016/j.2097-0927.202409151
  CLC： R341;R730.23;R735.2
- Received：30 September 2024，
  
  Revised：19 January 2025，
  
  Published：15 March 2025
- 稿件说明：
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任志祥，刘佳佳，覃中毅，等.钙腔蛋白对胃癌迁移、侵袭及患者预后的影响［J］.陆军军医大学学报，2025，47（05）：435-442.DOI：10.16016/j.2097-0927.202409151.

REN Z X，LIU J J，QIN Z Y，et al.Effect of calumenin on metastasis and invasion of gastric cancer and prognosis of patients［J］.J Army Med Univ，2025，47（05）：435-442.DOI：10.16016/j.2097-0927.202409151.
任志祥，刘佳佳，覃中毅，等.钙腔蛋白对胃癌迁移、侵袭及患者预后的影响［J］.陆军军医大学学报，2025，47（05）：435-442.DOI：10.16016/j.2097-0927.202409151. DOI：

REN Z X，LIU J J，QIN Z Y，et al.Effect of calumenin on metastasis and invasion of gastric cancer and prognosis of patients［J］.J Army Med Univ，2025，47（05）：435-442.DOI：10.16016/j.2097-0927.202409151. DOI：

摘要

目的

探究钙腔蛋白（calumenin， CALU）在胃癌中的表达及其对胃癌迁移、侵袭的影响，并分析其与胃癌患者预后的关系。

方法

利用癌症基因组图谱（the cancer genome atlas，TCGA）数据库分析CALU在胃癌中的表达水平及其对患者预后的影响。收集2018年1月至2022年12月在陆军军医大学第一附属医院普通外科进行胃部分切除术的189例胃癌患者的胃癌和癌旁组织样本102对。通过免疫组化实验检测CALU在胃癌和癌旁组织中的表达情况，并统计分析CALU表达与临床病理参数的关系。构建CALU敲低和过表达胃癌细胞株，通过Western blot以及RT-qPCR评估敲低及过表达效率。结合Transwell小室实验检测CALU对胃癌细胞的迁移、侵袭能力的影响。

结果

公共数据库结果分析发现CALU在胃癌组织中显著

高表达（

0.05），在95%置信区间下，CALU的表达水平与患者预后呈负相关（

0.05）。免疫组化结果发现相较于癌旁组织，CALU在胃癌组织中显著高表达（

0.01），其表达水平与浸润深度（

0.01）、淋巴结转移（

0.01）、TNM分期（

0.05）呈正相关，统计分析102例患者临床资料发现CALU的表达与TNM分期（

0.021）、T分期（

0.001）、N分期（

0.028）显著相关。CALU敲低可以显著的抑制胃癌细胞的迁移、侵袭能力（

0.01），而过表达则获得相反的结果。

结论

CALU在胃癌组织中高表达并促进胃癌的迁移、侵袭，进而导致胃癌患者的不良预后。

Abstract

Objective‍　‍To investigate the expression of calumenin (CALU) in gastric cancer and its effect on metastasis and invasion of gastric cancer

and analyze its relationship with the prognosis of gastric cancer patients. Methods‍　‍The Cancer Genome Atlas (TCGA) database was used to analyze the expression level of CALU in gastric cancer and its impact on patient prognosis. A total of 102 pairs of gastric cancer and paracancerous tissue samples were collected from 189 gastric cancer patients who underwent partial gastrectomy in First Affiliated Hospital of Army Medical University from January 2018 to December 2022. The expression of CALU in gastric cancer and paracancerous tissues was detected by immunohistochemical assay

and the relationship of its expression with clinicopathological parameters was statistically analyzed. After gastric cancer cells with CALU knockdown and overexpression were constructed

and the efficiencies of knockdown and overexpression were evaluated by Western blotting as well as RT-qPCR. Transwell assay was applied to determine the effect of CALU on the migration and invasion abilities of gastric cancer cells. Results‍　‍Bioinformation analysis found that CALU was significantly highly expressed in gastric cancer tissues (

0.05)

and its expression level was negatively correlated with the prognosis of patients (

0.05). Immunohistochemical results showed that the

expression level of CALU was obviously highly in gastric cancer tissues than the paracancerous tissues (

0.01)

and its level was positively correlated with the depth of infiltration (

0.01)

lymph node metastasis (

0.01)

and TNM stage (

0.05). Statistical analysis revealed that the clinical data of 102 patients showed that CALU expression was positively correlated with the TNM stage (

0.021) and T stage (

0.001) and N stage (

0.028). CALU knockdown significantly inhibited the migration and invasion abilities of gastric cancer cells (

0.01)

while over-expression obtained the opposite results. Conclusion‍　‍CALU is highly expressed in gastric cancer tissues and promotes metastasis and invasion of gastric cancer and thus leads to poor prognosis in patients.

关键词

Keywords

references

ZHENG R S ， ZHANG S W ， ZENG H M ， et al . Cancer incidence and mortality in China， 2016 ［J］. J Natl Cancer Cent ， 2022 ， 2 （ 1 ）： 1 - 9 . DOI： 10.1016/j.jncc.2022.02.002 http://dx.doi.org/10.1016/j.jncc.2022.02.002 .

LIU X ， HE Y D ， PENG Y ， et al . Metastasis of gastric carcinoma to the finger： report of a case ［J］. Zhonghua Bing Li Xue Za Zhi ， 2021 ， 50 （ 12 ）： 1407 - 1409 . DOI： 10.3760/cma.j.cn112151-20210520-00366 http://dx.doi.org/10.3760/cma.j.cn112151-20210520-00366 .

康鹏，张传宝，原林皓，等 . 钙腔蛋白基因在脑胶质瘤中的表达及其临床意义［J］. 中华神经外科杂志， 2020 ， 36 （ 2 ）： 130 - 135 . DOI： 10.3760/cma.j.issn.1001-2346.2020.02.005 http://dx.doi.org/10.3760/cma.j.issn.1001-2346.2020.02.005 .

KANG P ， ZHANG C B ， YUAN L H ， et al . Expression and clinical significance of calumenin in brain gliomas ［J］. Chin J Neurosurg ， 2020 ， 36 （ 2 ）： 130 - 135 . DOI： 10.3760/cma.j.issn.1001-2346.2020.02.005 http://dx.doi.org/10.3760/cma.j.issn.1001-2346.2020.02.005 .

黄侠，邱祥春，赵明 . 网腔钙结合蛋白的研究进展［J］. 生理科学进展， 2015 ， 46 （ 6 ）： 458 - 460 .

HUANG X ， QIU X C ， ZHAO M . Research progress of reticulum calcium binding protein ［J］. Prog Physiol Sci ， 2015 ， 46 （ 6 ）： 458 - 460 .

LEE J H ， KWON E J ， KIM D H . Calumenin has a role in the alleviation of ER stress in neonatal rat cardiomyocytes ［J］. Biochem Biophys Res Commun ， 2013 ， 439 （ 3 ）： 327 - 332 . DOI： 10.1016/j.bbrc.2013.08.087 http://dx.doi.org/10.1016/j.bbrc.2013.08.087 .

FENG H ， CHEN L ， WANG Q ， et al . Calumenin-15 facilitates filopodia formation by promoting TGF-β superfamily cytokine GDF-15 transcription ［J］. Cell Death Dis ， 2013 ， 4 （ 10 ）： e870 . DOI： 10.1038/cddis.2013.403 http://dx.doi.org/10.1038/cddis.2013.403 .

NAGANO K ， IMAI S ， ZHAO X ， et al . Identification and evaluation of metastasis-related proteins， oxysterol binding protein-like 5 and calumenin， in lung tumors ［J］. Int J Oncol ， 2015 ， 47 （ 1 ）： 195 - 203 . DOI： 10.3892/ijo.2015.3000 http://dx.doi.org/10.3892/ijo.2015.3000 .

KUNITA A ， MORITA S ， IRISA T U ， et al . MicroRNA-21 in cancer-associated fibroblasts supports lung adenocarcinoma progression ［J］. Sci Rep ， 2018 ， 8 （ 1 ）： 8838 . DOI： 10.1038/s41598-018-27128-3 http://dx.doi.org/10.1038/s41598-018-27128-3 .

DU Y H ， MIAO W H ， JIANG X ， et al . The epithelial to mesenchymal transition related gene calumenin is an adverse prognostic factor of bladder cancer correlated with tumor microenvironment remodeling， gene mutation， and ferroptosis ［J］. Front Oncol ， 2021 ， 11 ： 683951 . DOI： 10.3389/fonc.2021.683951 http://dx.doi.org/10.3389/fonc.2021.683951 .

许永虎，徐大志 . 21世纪以来胃癌治疗进展及未来展望［J］. 中国癌症杂志， 2024 ， 34 （ 3 ）： 239 - 249 . DOI： 10.19401/j.cnki.1007-3639.2024.03.001 http://dx.doi.org/10.19401/j.cnki.1007-3639.2024.03.001 .

XU Y H ， XU D Z . Progress and prospects of gastric cancer treatment in the 21st century ［J］. China Oncol ， 2024 ， 34 （ 3 ）： 239 - 249 . DOI： 10.19401/j.cnki.1007-3639.2024.03.001 http://dx.doi.org/10.19401/j.cnki.1007-3639.2024.03.001 .

PASECHNIKOV V ， CHUKOV S ， FEDOROV E ， et al . Gastric cancer： prevention， screening and early diagnosis ［J］. World J Gastroenterol ， 2014 ， 20 （ 38 ）： 13842 - 13862 . DOI： 10.3748/wjg.v20.i38.13842 http://dx.doi.org/10.3748/wjg.v20.i38.13842 .

JOHNSTON F M ， BECKMAN M . Updates on management of gastric cancer ［J］. Curr Oncol Rep ， 2019 ， 21 （ 8 ）： 67 . DOI： 10.1007/s11912-019-0820-4 http://dx.doi.org/10.1007/s11912-019-0820-4 .

HONORÉ B . The rapidly expanding CREC protein family： members， localization， function， and role in disease ［J］. Bioessays ， 2009 ， 31 （ 3 ）： 262 - 277 . DOI： 10.1002/bies. 200800186 http://dx.doi.org/10.1002/bies.200800186 .

NING J Y ， LIU M ， SHEN J ， et al . Expression signature and prognostic value of CREC gene family in human colorectal cancer ［J］. BMC Cancer ， 2023 ， 23 （ 1 ）： 878 . DOI： 10.1186/s12885-023-11303-5 http://dx.doi.org/10.1186/s12885-023-11303-5 .

TANG H ， MA M ， DAI J ， et al . MiR-let-7b and miR-let-7c suppress tumourigenesis of human mucosal melanoma and enhance the sensitivity to chemotherapy ［J］. J Exp Clin Cancer Res ， 2019 ， 38 （ 1 ）： 212 . DOI： 10.1186/s13046-019-1190-3 http://dx.doi.org/10.1186/s13046-019-1190-3 .

LI Y ， SUN S N ， ZHANG H ， et al . CALU promotes lung adenocarcinoma progression by enhancing cell proliferation， migration and invasion ［J］. Respir Res ， 2024 ， 25 （ 1 ）： 267 . DOI： 10.1186/s12931-024-02901-3 http://dx.doi.org/10.1186/s12931-024-02901-3 .

YANG Y ， WANG J ， XU S H ， et al . Calumenin contributes to epithelial-mesenchymal transition and predicts poor survival in glioma ［J］. Transl Neurosci ， 2021 ， 12 （ 1 ）： 67 - 75 . DOI： 10.1515/tnsci-2021-0004 http://dx.doi.org/10.1515/tnsci-2021-0004 .

TORRES S ， BARTOLOMÉ R A ， MENDES M ， et al . Proteome profiling of cancer-associated fibroblasts identifies novel proinflammatory signatures and prognostic markers for colorectal cancer ［J］. Clin Cancer Res ， 2013 ， 19 （ 21 ）： 6006 - 6019 . DOI： 10.1158/1078-0432.CCR-13-1130 http://dx.doi.org/10.1158/1078-0432.CCR-13-1130 .

ZHANG Y ， LIAO Y ， CHEN C Y ， et al . p38-regulated FOXC1 stability is required for colorectal cancer metastasis ［J］. J Pathol ， 2020 ， 250 （ 2 ）： 217 - 230 . DOI： 10.1002/path.5362 http://dx.doi.org/10.1002/path.5362 .

GE L ， LY Y ， HOLLENBERG M ， et al . A beta-arrestin-dependent scaffold is associated with prolonged MAPK activation in pseudopodia during protease-activated receptor-2-induced chemotaxis ［J］. J Biol Chem ， 2003 ， 278 （ 36 ）： 34418 - 34426 . DOI： 10.1074/jbc.M300573200 http://dx.doi.org/10.1074/jbc.M300573200

JIANG T L ， XIA Y W ， LV J L ， et al . A novel protein encoded by circMAPK1 inhibits progression of gastric cancer by suppressing activation of MAPK signaling ［J］. Mol Cancer ， 2021 ， 20 （ 1 ）： 66 . DOI： 10.1186/s12943-021-01358-y http://dx.doi.org/10.1186/s12943-021-01358-y .

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