CD44 splicing pattern is associated with disease progression in pulmonary adenocarcinoma
Journal
Journal of the Formosan Medical Association
Journal Volume
104
Journal Issue
8
Pages
541-548
Date Issued
2005
Author(s)
Abstract
Background and Purpose: Certain alternatively spliced exons of CD44 gene have been associated with specific functions. However, these functions may have come from inclusion of a central array of alternatively spliced exons, rather than a single one. The goals of this study were to analyze all of the variant exons included by alternative splicing, the entire population of CD44 mRNA transcripts, and the prognostic implications of CD44 mRNA and protein isoforms expressed by non-small cell lung cancer (NSCLC). Methods: Using a polymerase chain reaction protocol with short reaction times, we amplified, sequenced and quantified CD44 mRNA transcripts from 52 samples of NSCLC to determine the splicing patterns of alternatively included exons and the proportion of each CD44 mRNA transcript. The expression of CD44 standard form and variant isoforms CD44v3 and CD44v6 were also analyzed by immunohistochemistry (IHC). Results: Normal lung and NSCLC expressed CD44 mRNA transcripts containing variant exons v10, v8-10, v6-10, v3-10 and v2-10. In squamous cell carcinoma, the expression rates of these mRNA transcripts were equal to or higher than those of the normal lung, and the splicing pattern was not associated with disease progression. In adenocarcinoma, the expression rates of CD44v6-10, v3-10 and v2-10 mRNA were lower than in normal lung. The down-regulation of CD44v6-10, CD44v3-10 mRNA and CD44v6 protein paralleled the progression of adenocarcinoma. Recurrence of adenocarcinoma was associated with negative expression of CD44v6-10 or CD44v3-10 mRNA, and with low-level expression of CD44v6 or CD44v3 by IHC. Negative expression of CD44v6-10 mRNA and reduced expression of CD44v6 protein were associated with a shorter disease-free and overall survival in the univariate but not the multivariate analysis. Conclusion: Our data suggest that CD44 splicing pattern is associated with disease progression in adenocarcinoma.
SDGs
Other Subjects
CD44v antigen; CD44v3 antigen; CD44v6 antigen; unclassified drug; Hermes antigen; messenger RNA; adult; aged; alternative RNA splicing; article; cancer staging; cancer survival; controlled study; disease course; down regulation; exon; female; gene amplification; gene expression; gene sequence; human; human tissue; immunohistochemistry; lung adenocarcinoma; lung non small cell cancer; lung squamous cell carcinoma; major clinical study; male; overall survival; prognosis; reverse transcription polymerase chain reaction; adenocarcinoma; alternative RNA splicing; chemistry; gene expression regulation; genetics; lung; lung tumor; middle aged; mortality; pathology; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Alternative Splicing; Antigens, CD44; Carcinoma, Non-Small-Cell Lung; Disease Progression; Exons; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Lung; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; RNA, Messenger
Type
journal article