Abstract
Background and purposeCD44 variants have been associated with tumor invasion and metastasis, but CD44 expression patterns have not been systematically investigated in pancreatic carcinoma. This study systematically investigated whether CD44 expression patterns are involved in pancreatic carcinoma metastasis and prognosis.MethodsWe applied primers specific for all CD44 variants and CD44s to analyze the expression patterns of CD44 (CD44v2-CD44v10 and CD44s) using quantitative real-time PCR (qRT-PCR). We then further evaluated their roles in pancreatic carcinoma metastasis and prognosis using clinical survival analysis.ResultsIncreased CD44v expression and decreased CD44s expression were found in metastatic pancreatic carcinoma in three different cell lines and in human tumor tissue. Clinical analysis showed that CD44v6+ and CD44v9+ were correlated with lymph node metastasis, liver metastasis and TNM stage. However, CD44s− was associated with liver metastasis, tumor differentiation and TNM stage. Survival analysis showed that patients with CD44v6+/CD44s− or CD44v6+/CD44s− had lower overall survival (OS) rates, although the individual expression of CD44v6, CD44v9 and CD44s was also related to decreased OS rates. Univariate analysis showed that lymph node metastasis; vessel invasion; hepatic metastases; TNM stage; and individual or co-expression of CD44v6, CD44v9 and CD44s were risk factors affecting survival. Multivariate analysis showed that CD44v6+/CD44s− was an independent predictor of survival.ConclusionsWe found that CD44v6+, CD44v9+ and CD44s− were associated with pancreatic carcinoma metastasis and progression and that CD44v6+/CD44s− was an independent risk factor affecting survival in pancreatic carcinoma. Therefore, the different expression patterns of CD44v/CD44s may determine pancreatic carcinoma prognosis.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1579257224116287.
Highlights
Background and purposeCD44 variants have been associated with tumor invasion and metastasis, but CD44 expression patterns have not been systematically investigated in pancreatic carcinoma
Increased expression of CD44v and decreased expression of CD44s were associated with the invasion and metastatic potential of Pancreatic carcinoma (PCa) To analyze the expression levels of all CD44 variants, we first designed primers for each variant
CD44v6+ and CD44v9+ were correlated with lymph node metastasis, liver metastasis and TNM stage, and CD44s− was associated with liver metastasis and TNM stage. These results indicate that CD44v6+, CD44v9+ and CD44s− may be associated with poor prognosis in pancreatic carcinoma patients
Summary
Background and purposeCD44 variants have been associated with tumor invasion and metastasis, but CD44 expression patterns have not been systematically investigated in pancreatic carcinoma. This molecule is encoded by 20 exons and undergoes extensive alternative splicing to generate CD44s (CD44 standard) and CD44v (CD44 variants) [4,5,6]. The variable exons are typically numbered v1-v10 (v1 is not encoded in humans), corresponding to the genomic exons 6–15, and are alternatively spliced and incorporated into the variable region either singly or in combination. This process has the potential to generate thousands of different CD44 isoforms (Additional file 1: Figure S1) [6,7,8], and as a result, CD44 has complex and diverse functions
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