The protein calpain-9 may be an independent factor for poor prognosis that, when combined with TNM stage, may provide a better predictive model for outcomes in patients with gastric cancer, according to a study published in Scientific Reports.
Gastric cancer is the fifth most common type of cancer and the third leading cause of cancer-related death worldwide but is especially prevalent in Asia. While significant advances in treatment strategies and therapeutic options have been made, the prognosis of this patient population remains poor, with only ~23% surviving 5 years, highlighting the need for new molecular markers and cancer mechanisms that can be targeted by new therapeutic agents.
For that reason, Chinese researchers led by Zhenbin Shen, Zhongshan Hospital, Fudan University (Shanghai, China), conducted a study examining the expression of calpain-9 and calpain-8, proteins with protective functions in the mucous membrane of the of the stomach, in patients with gastric cancer to see if they were indicative of patient outcomes.
Tumor samples were obtained from 151 patients with gastric cancer who underwent gastrectomy without preoperative treatment at Zhongshan Hospital between 2004 and 2008. Hospital records were used to track clinicopathological features and survival data associated with each patient. Statistical models were also used to assess the predictive value of calpain 9 and 8 expression.
Researchers found that calpain-9 protein levels were decreased in tumorous tissue samples and calpain-8 expression was largely unchanged when compared with matched adjacent normal gastric tissue samples. Immunohistochemical assay confirmed these findings.
Additional analysis revealed that the overexpression of calpain-9 was also associated with cell cycle arrest in transfected in vitro gastric cancer cells while calpain-8 showed little influence on cell cycle progression or the expression of cell cycle-related proteins.
With these data in mind, researchers determined correlations between calpain-9 and clinicopathological features using the 151 gastric cancer samples. Overall, they found that calpain-9 expression was lower in the cancerous tissue than in the non-tumor gastric samples. Additionally, low expression of calpain-9 was found to be positively associated with male sex, late T stage, lymph node metastasis, and advanced TNM stage. In terms of survival, a Kaplan-Meier analysis revealed that high expression of calpain-9 correlated with prolonged survival. Further, when patients were divided into subgroups based on their TNM stage, calpain-9 expression was a statistically significant indicator of outcomes in patients with gastric cancer, indicating that a model incorporating these factors could provide more accurate prognoses.
“Our data suggested that calpain-9 could be useful as a new biomarker to establish the risk and prognosis of gastric cancer and to facilitate the selection of therapeutic modalities in clinical practice, as well as to propose a strategy to target calpain-9 as a potential adjuvant therapy for gastric cancer treatment,” researchers concluded.
However, they added that further research should be conducted to clarify the role of calpain-8 in gastric cancer prognosis and to identify ways in which these mechanisms could be targeted with therapeutic regimens in order to improve outcomes. —Sean McGuire