Elevated Expression of Calpain-4 Predicts Poor Prognosis in Patients with Gastric Cancer after Gastrectomy

Abstract

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.

Calpain Small Subunit 1 Protein in the Prognosis of Cancer Survivors and Its Clinicopathological Correlation

“…However, the potential value of Capn4 protein as a biomarker to predict clinical outcomes is still debatable. For example, Wu et al [10] reported that elevated expression of Capn4 was linked to poor prognosis as well as lymph node metastasis and deeper tumor invasion in esophageal cancer, which was consistent with the results in nasopharyngeal carcinoma [12], but no significant association was found between Capn4 protein expression and T stage in gastric cancer [13]. And Cheng et al [9] found that there was a significant relationship between Capn4 protein expression and TNM staging; however, in non-small cell lung cancer, no significant correlation was observed between Capn4 expression and tumor stage [14].…”

“…What is more important, it is reported that Capn4 is involved in tumor progression through many pathways, such as epithelial-mesenchymal transition (EMT), the FAK-Src signaling pathways, the Wnt/ -catenin ( -catenin), and the nuclear factor B (NF-B) signaling pathways [24,[30][31][32]. Additionally, Capn4 also correlates with drug response and tumor resistance and might serve as a potential therapeutic target for several kinds of tumors [13,14,33,34].…”

“…Characteristics. According to the selection criteria, eleven studies [9][10][11][12][13][14][20][21][22][23][24] were finally included into this meta-analysis, all included studies were retrospective studies from China, and a total of 1775 patients were recruited in this work. The sample size varied from 91 to 323.…”

Calpain‐2 triggers prostate cancer metastasis via enhancing CRMP4 promoter methylation through NF‐κB/DNMT1 signaling pathway

“…Interestingly, NF‐κB RelA/p65 enhances methylation of CpG islands on the promoter region and represses the transcription of certain tumor‐suppressor genes through recruitment of DNA methyltransferase‐1 (DNMT1) . Moreover, calpain proteins, a family of intracellular Ca2 ± dependent cysteine proteases are associated with the development and progression of a variety of tumors, such as breast cancer, gastric cancer . There is still controversy in the expression pattern of calpain in PCa samples due to the contradictory results of mRNA .…”

“…9 Moreover, calpain proteins, a family of intracellular Ca2 ± dependent cysteine proteases are associated with the development and progression of a variety of tumors, such as breast cancer, 10 gastric cancer. 11,12 There is still controversy in the expression pattern of calpain in PCa samples due to the contradictory results of mRNA. 13,14 In the previous study, we confirmed that calpain-2 also cleaves CRMP4, 15 but the functional modulation remains unclear.…”