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Updated: May 26, 2026
Multiomics Analysis of TMEM200A as a Pan-Cancer Biomarker
Published on: September 15, 2023
Immunohistochemical analysis of cell death pathways in gastrointestinal adenocarcinoma
Michiko Shintani1, Akiko Sangawa, Naoki Yamao
1Laboratory of Pathology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Japan. mtshin@kobe-u.ac.jp
Abstract:
Caspase-8 and caspase-9 play crucial roles in the extrinsic and intrinsic apoptotic pathways, respectively. The nuclear translocation of apoptosis-inducing factor (AIF) is involved in caspase-independent apoptosis. Microtubule-associated protein 1 light chain 3 (LC3) plays a pivotal role in autophagy. In the present study, we analyzed the expression of cleaved caspase-8 (CC8), cleaved caspase-9 (CC9), AIF, and LC3 in 160 gastrointestinal adenocarcinomas. The nuclear expression of AIF was rare. The expression of CC8 in gastric and colorectal adenocarcinomas did not differ, whereas the percentage of CC9-positive tumors in gastric adenocarcinomas was significantly higher than in colorectal adenocarcinomas. In contrast, the percentage of LC3-positive tumors in gastric adenocarcinomas was significantly lower than in colorectal adenocarcinomas. CC8 and CC9 occasionally co-existed in the same tumor cells in gastric adenocarcinoma. However, LC3-positive tumor cells in colorectal adenocarcinomas were constantly negative for CC8. No correlation was identified between the expression of any markers and clinicopathological parameters. These results suggest that different cell death pathways are activated in a manner that depends upon the primary site and cell type. The extrinsic and intrinsic apoptotic pathways may be mutually regulated in gastric adenocarcinomas. Also, autophagy may function as a cellular guardian to avoid apoptosis in colorectal adenocarcinomas.
Insights
This study reveals distinct cell death pathway activation in gastric versus colorectal adenocarcinomas. Gastric cancers show higher intrinsic apoptosis markers, while colorectal cancers exhibit more autophagy, suggesting site-specific cancer progression mechanisms.
Area of Science:
- Gastroenterology
- Oncology
- Cell Biology
Background:
- Apoptosis, crucial for cell death, involves extrinsic (caspase-8) and intrinsic (caspase-9) pathways.
- Caspase-independent apoptosis involves nuclear translocation of apoptosis-inducing factor (AIF).
- Autophagy, regulated by microtubule-associated protein 1 light chain 3 (LC3), is a cellular degradation process.
Purpose of the Study:
- To investigate the expression of key apoptosis and autophagy markers in gastrointestinal adenocarcinomas.
- To compare the activation patterns of these pathways between gastric and colorectal adenocarcinomas.
- To explore potential correlations between marker expression and clinicopathological features.
Main Methods:
- Analysis of cleaved caspase-8 (CC8), cleaved caspase-9 (CC9), AIF, and LC3 expression in 160 gastrointestinal adenocarcinomas.
- Immunohistochemical assessment of protein expression and localization.
- Statistical comparison of marker positivity between gastric and colorectal tumor cohorts.
Main Results:
- Nuclear AIF expression was infrequent across all samples.
- Gastric adenocarcinomas showed a significantly higher percentage of CC9-positive tumors compared to colorectal adenocarcinomas.
- Gastric adenocarcinomas had a lower percentage of LC3-positive tumors than colorectal adenocarcinomas, with CC8 and CC9 co-expression observed.
- Colorectal adenocarcinomas displayed LC3-positive cells that were consistently negative for CC8.
Conclusions:
- Cell death pathway activation differs significantly between gastric and colorectal adenocarcinomas, influenced by primary site and cell type.
- The extrinsic and intrinsic apoptotic pathways may be mutually regulated in gastric adenocarcinomas.
- Autophagy appears to act as a protective mechanism against apoptosis in colorectal adenocarcinomas.