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Updated: Jun 26, 2026
Colorectal Cancer Cell Surface Protein Profiling Using an Antibody Microarray and Fluorescence Multiplexing
Published on: September 25, 2011
Clinical significance of Smac/DIABLO expression in colorectal cancer
Kazuya Endo1, Shunji Kohnoe, Akihiro Watanabe
1Department of Surgery and Science, Kyushu University, Fukuoka 812-8582, Japan. k-endo@surg2.med.kyushu-u.ac.jp
Abstract:
Second mitochondria-derived activator of caspases/direct inhibitor of apoptosis-binding protein with low pI (Smac/DIABLO) is released by mitochondria in response to apoptotic stimuli and is thought to regulate apoptosis by antagonizing inhibitors of apoptosis proteins, which play an important role in sensitization of cancer cells to various therapeutic regimens. The expression of Smac/DIABLO has been demonstrated in various cancer cells, though little is known about its clinical significance with respect to colorectal cancer. The current study was designed to evaluate the relationship between prognosis and Smac/DIABLO expression by clinicopathological analysis of patients with colorectal cancer. Smac/DIABLO expression was evaluated using immunohistochemical staining in 121 consecutive patients with colorectal cancer and the relationship between Smac/DIABLO expression and clinicopathological factors was analyzed. Smac/DIABLO-positive expression was detected in 80 of the 121 patients (66%). The incidence of lymph node and distant metastasis in Smac/DIABLO-negative cancer was significantly higher than that in Smac/DIABLO-positive cancer (P=0.0004 and P=0.003, respectively). While univariate analysis showed that survival in patients with Smac/DIABLO-negative expression was significantly poorer than in Smac/DIABLO-positive cases (P<0.0001), Smac/DIABLO-negative expression was a prognostic indicator independent of Dukes' staging and lymph node metastasis by multivariate analysis. This study proposes that the decrease of Smac/DIABLO expression is an independent factor determining the poorer prognosis of patients with colorectal cancer.
Insights
Decreased expression of Smac/DIABLO (second mitochondria-derived activator of caspases/direct inhibitor of apoptosis-binding protein with low pI) is linked to poorer prognosis in colorectal cancer patients. Lower Smac/DIABLO levels correlate with increased metastasis and reduced survival rates.
Area of Science:
- Molecular Biology
- Oncology
- Cell Death Pathways
Background:
- Second mitochondria-derived activator of caspases/direct inhibitor of apoptosis-binding protein with low pI (Smac/DIABLO) regulates apoptosis by inhibiting apoptosis inhibitors.
- Smac/DIABLO's role in colorectal cancer prognosis is not well-established.
- Apoptosis regulation is crucial for cancer therapy sensitization.
Purpose of the Study:
- To investigate the clinical significance of Smac/DIABLO expression in colorectal cancer.
- To evaluate the relationship between Smac/DIABLO expression and patient prognosis.
- To determine if Smac/DIABLO expression is an independent prognostic factor.
Main Methods:
- Immunohistochemical staining of Smac/DIABLO in 121 colorectal cancer patient samples.
- Clinicopathological analysis correlating Smac/DIABLO expression with prognostic factors.
- Univariate and multivariate survival analyses.
Main Results:
- Smac/DIABLO-positive expression was observed in 66% of patients.
- Smac/DIABLO-negative expression was associated with significantly higher rates of lymph node and distant metastasis.
- Univariate analysis revealed poorer survival in Smac/DIABLO-negative cases (P<0.0001).
Conclusions:
- Decreased Smac/DIABLO expression is an independent prognostic indicator of poorer outcomes in colorectal cancer.
- Smac/DIABLO expression levels may predict disease progression and patient survival.
- Targeting Smac/DIABLO pathways could be a therapeutic strategy for colorectal cancer.