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Reduced expression of lamin A/C correlates with poor histological differentiation and prognosis in primary gastric carcinoma

DOI: 10.1186/1756-9966-28-8

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Abstract:

The expression of lamin A/C at mRNA level was detected by the reverse transcription-polymerase chain reaction (RT-PCR) and real time RT-PCR, and western blot was used to examine the protein expression. Lamin A/C expression and its prognostic significance were investigated by performing immunohistochemical analysis on a total of 126 GC clinical tissue samples.Both lamin A/C mRNA and protein expression were downregulated in the majority of tumours compared with corresponding normal gastric tissues (p = 0.011 and p = 0.036, respectively). Real time RT-PCR further validated that downregulation of lamin A/C is associated with poor histological differentiation (r = 0.438, p = 0.025). The immunohistochemical staining showed an evident decrease of lamin A/C expression in 55.6% (70/126) GC cases. Importantly, the negative lamin A/C expression correlated strongly with histological classification (r = 0.361, p = 0.034). Survival analysis revealed that patients with lamin A/C downregulation have a poorer prognosis (p = 0.034). In addition, lamin A/C expression was found to be an independent prognostic factor by multivariate analysis.Data of this study suggest that lamin A/C is involved in the pathogenesis of GC, and it may serve as a valuable biomarker for assessing the prognosis for primary GC.The A-type lamins (predominantly lamins A and C, two alternatively spliced products of the LMNA gene), along with B-type lamins (members of the intermediate filament proteins), are the most principal components of the nuclear lamina-a proteinaceous meshwork of 10 nm diameter filaments lying at the interface between chromatin and the inner nuclear membrane. The nuclear lamina is thought to be a principal determinant of nuclear architecture. Downregulation or specific mutations in lamins cause abnormal nuclear shape, changes in heterochromatin localization at the nuclear periphery, global chromatin reorganization and possibly specific changes in the positions of genes [1]. It is possible t

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