Smac/DIABLO expression in human gastrointestinal carcinoma: Association with clinicopathological parameters and survivin expression

Shintani,Michiko; Sangawa,Akiko; Yamao,Naoki; Kamoshida,Shingo

doi:10.3892/ol.2014.2598

Smac/DIABLO expression in human gastrointestinal carcinoma: Association with clinicopathological parameters and survivin expression

Authors:
- Michiko Shintani
- Akiko Sangawa
- Naoki Yamao
- Shingo Kamoshida
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Affiliations: Laboratory of Pathology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Hyogo 654‑0142, Japan, Department of Clinical Laboratory, Kuma Hospital, Kobe, Hyogo 650‑0011, Japan
Published online on: October 9, 2014 https://doi.org/10.3892/ol.2014.2598
Pages: 2581-2586

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Abstract

Lack of apoptosis is a key factor in carcinogenesis and tumor progression. Survivin is a member of the inhibitor of apoptosis protein (IAP) family. Second mitochondria‑derived activator of caspases/direct inhibitor of apoptosis‑binding protein with low pI (Smac/DIABLO) is an antagonist of IAPs. Recently, Smac/DIABLO was identified as a potent therapeutic target. However, the clinical significance of Smac/DIABLO in gastrointestinal carcinomas remains unclear. In the present study, Smac/DIABLO expression was analyzed by immunohistochemistry in 72 gastric adenocarcinomas and 78 colorectal adenocarcinomas. The expression of Smac/DIABLO was significantly higher in colorectal carcinoma than in gastric carcinoma. Additionally, a correlation was found between the expression of Smac/DIABLO and nuclear survivin in well‑ to moderately‑differentiated colorectal adenocarcinomas (r=0.245; P<0.01). Based on these results, it was hypothesized that gastric and colorectal carcinomas differ in the level of Smac/DIABLO expression. Our previous studies revealed that the expression of cleaved caspase‑9 was significantly lower in colorectal carcinoma than in gastric carcinoma (P<0.0001). Conversely, the expression levels of microtubule‑associated protein 1 light chain 3 (LC3), an autophagy marker, and survivin were significantly higher in colon cancer than in gastric cancer (P<0.0001 and P<0.01, respectively). Taken together, these results indicate that not only LC3 and survivin expression, but also Smac/DIABLO expression, are significantly higher in colorectal carcinoma than in gastric carcinoma. We hypothesize that the analysis of Smac/DIABLO, survivin and LC3 expression in colorectal carcinoma is likely to aid cancer therapy due to the involvement of these markers in apoptosis and/or autophagy.

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