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Beclin 1 over- and underexpression in colorectal cancer: distinct patterns relate to prognosis and tumour hypoxia.

Koukourakis MI, Giatromanolaki A, Sivridis E, Pitiakoudis M, Gatter KC, Harris AL - Br. J. Cancer (2010)

Bottom Line: Extensive overexpression of Beclin 1 was significantly linked with overexpression of HIF1α and LDH5, as well as with high histological grade, vascular invasion and nodal involvement.Furthermore, patients with extensive over- or underexpression of Beclin 1 had a significantly poorer overall survival compared with the other two groups (P<0.0001).Beclin 1 has an important role in growth and metastasis of colorectal cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiotherapy/Oncology, Democritus University of Thrace and University General Hospital of Alexandroupolis, Alexandroupolis, 68100, Greece. targ@her.forthnet.gr

ABSTRACT

Introduction: Autophagy enables cells to recycle long-lived proteins or damaged organelles. Beclin 1, the mammalian orthologue of the yeast Apg6/Vps30 gene, functions as a scaffold for the formation of autophagosomes.

Materials and method: The immunohistochemical patterns of Beclin 1 expression and their prognostic relevance were studied in formalin-fixed tissues from 155 patients with colorectal adenocarcinoma treated with surgery alone.

Results: Using the weak homogeneous expression of Beclin 1 in normal colonic tissues as a basis for assessing tumours, the following grouping/staining patterns were recognised in colorectal carcinomas: a normal-like pattern in 62 of 155 (40%) cases, an underexpression pattern in 24 of 155 (15.5%) cases, extensive overexpression of Beclin 1 in 33 of 155 (21.3%) tumours and limited overexpression of the protein in 36 of 155 (23.2%) tumours. Extensive overexpression of Beclin 1 was significantly linked with overexpression of HIF1α and LDH5, as well as with high histological grade, vascular invasion and nodal involvement. Furthermore, patients with extensive over- or underexpression of Beclin 1 had a significantly poorer overall survival compared with the other two groups (P<0.0001). Beclin 1 had an independent prognostic relevance in multivariate analysis.

Conclusions: Beclin 1 has an important role in growth and metastasis of colorectal cancer. Loss of Beclin 1 expression (allelic loss or microRNA regulatory activity, as suggested in the literature) defines poor prognosis presumably by promoting anti-apoptotic pathways, while overexpression of the protein, being linked with tumour hypoxia and acidity, also defines subgroups of tumours with aggressive clinical behaviour.

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Related in: MedlinePlus

Kaplan–Meier overall survival curves according to the cytoplasmic patterns (A) and the nuclear expression (B). Pts, patients.
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fig2: Kaplan–Meier overall survival curves according to the cytoplasmic patterns (A) and the nuclear expression (B). Pts, patients.

Mentions: Figure 2A shows Kaplan–Meier disease-specific OS curves, stratified according to the cytoplasmic expression patterns. Patients with extensive overexpression and those with underexpression of Beclin 1 had a significantly poorer OS compared with other two groups (P<0.0001). The 3-year OS was 89%, 77.7%, 43.3% and 31% for patients exhibiting normal-like, limited overexpression, extensive overexpression and underexpression patterns, respectively. The nuclear expression of Beclin 1 was not related to prognosis (Figure 2B).


Beclin 1 over- and underexpression in colorectal cancer: distinct patterns relate to prognosis and tumour hypoxia.

Koukourakis MI, Giatromanolaki A, Sivridis E, Pitiakoudis M, Gatter KC, Harris AL - Br. J. Cancer (2010)

Kaplan–Meier overall survival curves according to the cytoplasmic patterns (A) and the nuclear expression (B). Pts, patients.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2967071&req=5

fig2: Kaplan–Meier overall survival curves according to the cytoplasmic patterns (A) and the nuclear expression (B). Pts, patients.
Mentions: Figure 2A shows Kaplan–Meier disease-specific OS curves, stratified according to the cytoplasmic expression patterns. Patients with extensive overexpression and those with underexpression of Beclin 1 had a significantly poorer OS compared with other two groups (P<0.0001). The 3-year OS was 89%, 77.7%, 43.3% and 31% for patients exhibiting normal-like, limited overexpression, extensive overexpression and underexpression patterns, respectively. The nuclear expression of Beclin 1 was not related to prognosis (Figure 2B).

Bottom Line: Extensive overexpression of Beclin 1 was significantly linked with overexpression of HIF1α and LDH5, as well as with high histological grade, vascular invasion and nodal involvement.Furthermore, patients with extensive over- or underexpression of Beclin 1 had a significantly poorer overall survival compared with the other two groups (P<0.0001).Beclin 1 has an important role in growth and metastasis of colorectal cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiotherapy/Oncology, Democritus University of Thrace and University General Hospital of Alexandroupolis, Alexandroupolis, 68100, Greece. targ@her.forthnet.gr

ABSTRACT

Introduction: Autophagy enables cells to recycle long-lived proteins or damaged organelles. Beclin 1, the mammalian orthologue of the yeast Apg6/Vps30 gene, functions as a scaffold for the formation of autophagosomes.

Materials and method: The immunohistochemical patterns of Beclin 1 expression and their prognostic relevance were studied in formalin-fixed tissues from 155 patients with colorectal adenocarcinoma treated with surgery alone.

Results: Using the weak homogeneous expression of Beclin 1 in normal colonic tissues as a basis for assessing tumours, the following grouping/staining patterns were recognised in colorectal carcinomas: a normal-like pattern in 62 of 155 (40%) cases, an underexpression pattern in 24 of 155 (15.5%) cases, extensive overexpression of Beclin 1 in 33 of 155 (21.3%) tumours and limited overexpression of the protein in 36 of 155 (23.2%) tumours. Extensive overexpression of Beclin 1 was significantly linked with overexpression of HIF1α and LDH5, as well as with high histological grade, vascular invasion and nodal involvement. Furthermore, patients with extensive over- or underexpression of Beclin 1 had a significantly poorer overall survival compared with the other two groups (P<0.0001). Beclin 1 had an independent prognostic relevance in multivariate analysis.

Conclusions: Beclin 1 has an important role in growth and metastasis of colorectal cancer. Loss of Beclin 1 expression (allelic loss or microRNA regulatory activity, as suggested in the literature) defines poor prognosis presumably by promoting anti-apoptotic pathways, while overexpression of the protein, being linked with tumour hypoxia and acidity, also defines subgroups of tumours with aggressive clinical behaviour.

Show MeSH
Related in: MedlinePlus