Elevated Expression of Calpain-4 Predicts Poor Prognosis in Patients with Gastric Cancer after Gastrectomy.
Calpain-4 belongs to the calpain family of calcium-dependent cysteine proteases, and functions as a small regulatory subunit of the calpains. Recent evidence indicates that calpain-4 plays critical roles in tumor migration and invasion. However, the roles of calpain-4 in gastric tumorigenesis remain poorly understood. Herein, we examined calpain-4 expression by immunohistochemical staining on tissue microarrays containing tumor samples of 174 gastric cancer patients between 2004 and 2008 at a single center. The Kaplan-Meier method was used to compare survival curves, and expression levels were correlated to clinicopathological factors and overall survival. Our data demonstrated that calpain-4 was generally increased in gastric cancer cell lines and primary tumor tissues. High expression of calpain-4 was positively associated with vessel invasion, lymph node metastasis, and advanced TNM (Tumor Node Metastasis) stage. Multivariate analysis identified calpain-4 as an independent prognostic factor for poor prognosis. A predictive nomogram integrating calpain-4 expression with other independent prognosticators was constructed, which generated a better prognostic value for overall survival of gastric cancer patients than a TNM staging system. In conclusion, calpain-4 could be regarded as a potential prognosis indicator for clinical outcomes in gastric cancer.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. 14111010028@fudan.edu.cn.
Peike
P
Peng
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China. minlingqiang@163.com.
Lingqiang
L
Min
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. songshus@126.com.
Shushu
S
Song
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China. 14111210064@fudan.edu.cn.
Junjie
J
Zhao
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. 13111010011@fudan.edu.cn.
Lili
L
Li
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. 15111010021@fudan.edu.cn.
Caiting
C
Yang
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. 12111010008@fudan.edu.cn.
Miaomiao
M
Shao
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. 14111010031@fudan.edu.cn.
Mingming
M
Zhang
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. 15211010029@fudan.edu.cn.
Hao
H
Wu
Institute of Biomedical Science, Fudan University, Shanghai 200032, China. 15211510023@fudan.edu.cn.
Jie
J
Zhang
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. 14111010002@fudan.edu.cn.
Can
C
Li
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China. wang.xuefei@zs-hospital.sh.cn.
Xuefei
X
Wang
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China. hongshanwang@fudan.edu.cn.
Hongshan
H
Wang
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China. qin.jing@zs-hospital.sh.cn.
Jing
J
Qin
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. yuanyuanruan@fudan.edu.cn.
Yuanyuan
Y
Ruan
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. gjxjxg@126.com.|Institute of Biomedical Science, Fudan University, Shanghai 200032, China. gjxjxg@126.com.
Jianxin
J
Gu
biomarker; calpain-4; gastric cancer; nomogram; overall survival; prognosis
PLoS One. 2013;8(1):e54619
23349941
J Clin Oncol. 2005 Sep 1;23(25):6220-32
16135489
J Int Med Res. 2014 Apr;42(2):282-91
24514433
Cancer Res. 2004 Oct 15;64(20):7237-40
15492240
J Biol Chem. 2001 Dec 21;276(51):48382-8
11602605
Nat Rev Cancer. 2011 May;11(5):364-74
21508973
Mol Cell Biol. 2000 Jun;20(12):4474-81
10825211
J Biol Chem. 2008 Jul 25;283(30):21002-10
18515801
Gastroenterology. 2013 Sep;145(3):505-8
23891604
Genome Biol. 2010;11(3):R25
20196867
Gastroenterology. 2016 May;150(5):1183-1195.e16
26855187
J Biol Chem. 2005 Feb 25;280(8):6879-89
15611136
EMBO J. 2003 Jul 1;22(13):3346-55
12839996
Cancer Sci. 2014 Jun;105(6):630-8
24703594
CA Cancer J Clin. 2015 Mar;65(2):87-108
25651787
Diabetes. 2004 Feb;53 Suppl 1:S12-8
14749260
J Biochem. 1986 May;99(5):1525-32
3011775
Endocrinology. 2005 May;146(5):2336-44
15691895
J Clin Oncol. 2014 May 20;32(15):1521-30
24752046
Med Oncol. 2015 Mar;32(3):51
25636510
Arch Biochem Biophys. 2014 Dec 15;564:26-36
25305531
Cancer Res. 2015 Sep 15;75(18):3832-41
26199092
Ann Surg Oncol. 2010 Jun;17(6):1471-4
20180029
Sci Rep. 2016 Jul 12;6:29604
27404891
Nat Methods. 2014 Jun;11(6):599-600
24874569
Int J Oncol. 2014 Feb;44(2):467-72
24297527
Exp Anim. 2010;59(5):549-66
21030783
Nat Med. 2015 May;21(5):449-56
25894828
CNS Neurosci Ther. 2014 Jun;20(6):521-7
24628706
J Pathol. 2014 Nov;234(3):316-28
24962955
Physiol Rev. 2003 Jul;83(3):731-801
12843408
Gene. 2005 Oct 24;360(1):1-19
16154715