Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
Department of Pathology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
Clin Transl Oncol. 2019 Jul;21(7):924-932. doi: 10.1007/s12094-018-02006-6. Epub 2018 Dec 18.
Pancreatic cancer (PC) is a highly aggressive and metastatic disease, with an elevated mortality rate. It is, therefore, crucial to assess factors affecting the prognosis of PC patients. Meanwhile, calpain-1 is associated with malignant tumor progression and metastasis. Thus, it is meaningful to evaluate the relationship between calpain-1 and PC.
Calpain-1 protein expression was assessed by immunohistochemistry in 96 pancreatic cancer samples and paired adjacent non-cancerous specimens. In addition, calpain-1 protein levels were assessed in six PC cell lines by western blot (WB). Next, PC cells were transfected with calpain-1 siRNA, and silencing was confirmed by WB. Finally, cell proliferation, colony formation, migration and invasion assays, and cell apoptosis analysis were performed to examine the effects of calpain-1 knockdown on proliferation, growth, apoptosis, migration, and invasion in PC cells.
The results showed that calpain-1 was overexpressed in PC tissues and cells. Meanwhile, calpain-1 overexpression was associated with tumor site (P = 0.029), metastasis (P = 0.000), and TNM stage (P = 0.000), but showed no associations with histological grade (P = 0.396), age (P = 0.809), sex (P = 1.000), and lesion size (P = 0.679). The Kaplan-Meier method demonstrated that the low calpain-1 expression group had increased overall survival (OS) compared with patients expressing high calpain-1 levels (28.7 ± 4.1 vs. 17.0 ± 2.3 months) (P = 0.005). Besides, calpain-1 in PC cells was successfully silenced by liposome-mediated RNA interference, resulting in reduced cell growth, invasion, and metastasis in PC cells, with no effect on apoptosis.
The above findings suggest that calpain-1 should be considered a potential biomarker for PC prognosis and therapy.
胰腺癌（PC）是一种侵袭性和转移性很强的疾病，死亡率很高。因此，评估影响 PC 患者预后的因素至关重要。同时，钙蛋白酶-1 与恶性肿瘤的进展和转移有关。因此，评估钙蛋白酶-1 与 PC 的关系具有重要意义。
采用免疫组织化学法检测 96 例胰腺癌组织及其配对的癌旁非肿瘤组织中钙蛋白酶-1 蛋白的表达，并采用 Western blot（WB）法检测 6 株 PC 细胞系中钙蛋白酶-1 蛋白的水平。然后，用钙蛋白酶-1 siRNA 转染 PC 细胞，并用 WB 验证沉默效果。最后，通过细胞增殖、集落形成、迁移和侵袭实验以及细胞凋亡分析，研究钙蛋白酶-1 敲低对 PC 细胞增殖、生长、凋亡、迁移和侵袭的影响。
结果表明，钙蛋白酶-1 在 PC 组织和细胞中过表达。同时，钙蛋白酶-1 过表达与肿瘤部位（P=0.029）、转移（P=0.000）和 TNM 分期（P=0.000）有关，而与组织学分级（P=0.396）、年龄（P=0.809）、性别（P=1.000）和病变大小（P=0.679）无关。Kaplan-Meier 法表明，低钙蛋白酶-1 表达组的总生存（OS）较高钙蛋白酶-1 表达组患者延长（28.7±4.1 个月比 17.0±2.3 个月）（P=0.005）。此外，通过脂质体介导的 RNA 干扰成功沉默 PC 细胞中的钙蛋白酶-1，导致 PC 细胞的生长、侵袭和转移减少，但对细胞凋亡无影响。
上述结果表明，钙蛋白酶-1 可作为 PC 预后和治疗的潜在生物标志物。
