Abstract
Casitas B-lineage lymphoma b (Cbl-b) is a ubiquitin-protein ligase and a signal transducing adaptor protein involved in immune regulation, and it may be involved in the development and progression of cancer. We investigated the association between Cbl-b expression and prognosis in patients with resectable pancreatic ductal adenocarcinoma (PDAC). The clinicopathological characteristics and survival data of 134 patients with surgery for PDAC between January 2009 and February 2012 were retrospectively evaluated, and Cbl-b expression was assayed by immunohistochemical staining. The association of Cbl-b expression with clinicopathological features and postoperative prognosis was analyzed. Cbl-b expression was strongly associated with the pathological primary tumor (pT) category (P = 0.005) and pathological TNM (pTNM) stage (P = 0.035), but not with other clinicopathological characteristics (all P > 0.05). In addition to current markers including pathological regional lymph nodes (pN) category, CA19-9, and histological differentiation, univariate and multivariate analysis found that Cbl-b was independently associated with overall survival (OS) of patients with resectable PDAC. Cbl-b was predictive of OS in a subgroup of patients with serum CA19-9 ≥ 37 U/mL. Cbl-b expression combined with pN, histological differentiation, and CA19-9 level could be used as a novel clinical model predictive of OS for patients with resectable PDAC. In conclusion, Cbl-b in resectable PDAC was an independent predictor of adverse prognosis. Cbl-b expression together with pN, histological differentiation, and CA19-9 level might lead to improved risk stratification and prognosis for patients with resectable PDAC.
Highlights
Despite advances in treatment, the prognosis of pancreatic cancer is dismal, and the 5-year survival rate is < 7% [1]
We found that silencing of Casitas B-lineage lymphoma b (Cbl-b) expression inhibited proliferation in pancreatic ductal adenocarcinoma (PDAC) cells in vitro [9]
We investigated the prognostic value of Cbl-b by retrospectively evaluating the relationship of Cbl-b expression with the clinicopathological characteristics and survival of PDAC patients
Summary
The prognosis of pancreatic cancer is dismal, and the 5-year survival rate is < 7% [1]. For patients with pancreatic cancer, surgical resection is the only curative treatment, but fewer than 20% of patients are indicated for radical surgery, and their 5-year survival rate is only 10%–25%[3, 4]. Various biomarkers have been reported to be the prognostic markers for pancreatic cancer. Despite being a hypovascular malignant tumor, pancreatic cancer cells are still capable of rapid proliferation. Li et al reported that presence of the rs2305035, a variant AA or AG genotypes was associated with overall survival (OS) [16], and patients with Cbl family mutations (e.g., c-Cbl, Cbl-b, and Cbl-c) for myeloid malignancies had poor prognosis [17]. If a relationship between Cbl-b expression and the prognosis in PDAC does exist, interfering with Cbl-b expression or the Cbl-b signal pathway may be able to prolong survival of PDAC patients, and shed light on potential therapeutic targets and prognostic biomarkers
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