P Singh1, J D Wig, R Srinivasan, B D Radotra. 1. School of Molecular and Microbial Biosciences, The University of Sydney, NSW, 2006, Australia. puneetsingh_bio@y7mail.com
Abstract
BACKGROUND: Smad4, Smad6 and Smad7 are important molecules in TGF-beta pathway, which plays an important role in pancreatic ductal adenocarcinoma (PDAC) biology. Aims : This study examined the expression profiles of Smad4, Smad6 and Smad7 mRNA in patient samples of PDAC and their relationship to Smad protein expression, SMAD4 gene mutations, clinicopathological parameters and patient survival. SETTINGS AND DESIGN: Surgically resected, paired normal and tumor tissues of 25 patients of PDAC were studied. MATERIALS AND METHODS: Protein and mRNA levels were assessed by immunohistochemistry and RT-PCR, respectively. STATISTICAL METHODS: Statistical analysis was done using Student's t-test, Pearson's chi-square test, Spearman's Rank Correlation, Pearson's Correlation test and Kaplan-Meier Logrank test. RESULTS: While there was a highly significant difference in the protein levels of all three Smads in tumor as compared to normal samples, mRNA levels were significantly different only for Smad4. Protein levels did not correlate significantly with mRNA levels for any of the three Smads. The mRNA levels of Smad4 and Smad6, Smad4 and Smad7, and Smad6 and Smad7 in tumor samples showed a significant positive correlation. The relationship of Smad4 mRNA expression to SMAD4 gene status and Smad4 protein expression was discordant and there was no significant correlation between mRNA expression and clinicopathological parameters and patient survival. CONCLUSION: The absence of concordance between SMAD4 gene status, mRNA expression and Smad4 protein expression suggests the presence of other regulatory mechanisms in Smad4 transcription and translation in PDAC.
BACKGROUND:Smad4, Smad6 and Smad7 are important molecules in TGF-beta pathway, which plays an important role in pancreatic ductal adenocarcinoma (PDAC) biology. Aims : This study examined the expression profiles of Smad4, Smad6 and Smad7 mRNA in patient samples of PDAC and their relationship to Smad protein expression, SMAD4 gene mutations, clinicopathological parameters and patient survival. SETTINGS AND DESIGN: Surgically resected, paired normal and tumor tissues of 25 patients of PDAC were studied. MATERIALS AND METHODS: Protein and mRNA levels were assessed by immunohistochemistry and RT-PCR, respectively. STATISTICAL METHODS: Statistical analysis was done using Student's t-test, Pearson's chi-square test, Spearman's Rank Correlation, Pearson's Correlation test and Kaplan-Meier Logrank test. RESULTS: While there was a highly significant difference in the protein levels of all three Smads in tumor as compared to normal samples, mRNA levels were significantly different only for Smad4. Protein levels did not correlate significantly with mRNA levels for any of the three Smads. The mRNA levels of Smad4 and Smad6, Smad4 and Smad7, and Smad6 and Smad7 in tumor samples showed a significant positive correlation. The relationship of Smad4 mRNA expression to SMAD4 gene status and Smad4 protein expression was discordant and there was no significant correlation between mRNA expression and clinicopathological parameters and patient survival. CONCLUSION: The absence of concordance between SMAD4 gene status, mRNA expression and Smad4 protein expression suggests the presence of other regulatory mechanisms in Smad4 transcription and translation in PDAC.
Authors: David J Birnbaum; Sebastian K S Begg; Pascal Finetti; Charles Vanderburg; Anupriya S Kulkarni; Azfar Neyaz; Thomas Hank; Eric Tai; Vikram Deshpande; François Bertucci; Daniel Birnbaum; Keith D Lillemoe; Andrew L Warshaw; Mari Mino-Kenudson; Carlos Fernandez-Del Castillo; David T Ting; Andrew S Liss Journal: Clin Cancer Res Date: 2021-02-05 Impact factor: 13.801