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Autophagy-based survival prognosis in human colorectal carcinoma.

Yang M, Zhao H, Guo L, Zhang Q, Zhao L, Bai S, Zhang M, Xu S, Wang F, Wang X, Zhao B - Oncotarget (2015)

Bottom Line: We developed an autophagy signature for prognosis based on these three major autophagic proteins, further analysis suggested it was an independent prognostic biomarker and had its value even within single clinical stage.Combined TNM stage and this signature could significantly improve the accuracy of survival prognosis.Our findings suggest that autophagy plays an important role in the clinical cancer progression.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Heilongjiang, China.

ABSTRACT
The role of autophagy in cancers is controversial. Here we aim to determine the prognostic significance of autophagy in colorectal carcinoma patients, thereby allowing more rational development of therapeutic strategies. Through transmission electron microscopy, our data first demonstrated high frequency of defective mitochondria was strongly associated with poor overall survival in colorectal carcinoma. Next immunohistochemical study showed the expressions of Beclin 1, LC3B and Bcl-xL in both the center of tumor and adjacent noncancerous mucosal region were also correlated with overall survivals. We developed an autophagy signature for prognosis based on these three major autophagic proteins, further analysis suggested it was an independent prognostic biomarker and had its value even within single clinical stage. Combined TNM stage and this signature could significantly improve the accuracy of survival prognosis. To validate these immunohistochemical results, an internal testing cohort and an independent population were also included. Our findings suggest that autophagy plays an important role in the clinical cancer progression. Therefore autophagic proteins may be valuable prognostic biomarkers in the therapy of colorectal carcinoma and possibly other types of cancers.

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Related in: MedlinePlus

Overall survivals and expression of three autophagic proteins in both the center of tumor (CT) area and noncancerous mucosal (NM) region(A) Representative examples of Beclin 1, LC3B and Bcl-xL immunostaining in CT (lower panel) and NM (upper panel) (magnification, X200). (B) Comparison of the mean (±SE) of autophagic protein expression scores in CT and NM from patients who were dead (black bars) or patients who were survive (white bars). (C) Overall survival time for patients with high atuophagic protein expressions (blue bars) or low protein expressions (red bars) in CT or NM region. **, p < 0.01; ***, p < 0.001; NS, p > 0.05
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Figure 2: Overall survivals and expression of three autophagic proteins in both the center of tumor (CT) area and noncancerous mucosal (NM) region(A) Representative examples of Beclin 1, LC3B and Bcl-xL immunostaining in CT (lower panel) and NM (upper panel) (magnification, X200). (B) Comparison of the mean (±SE) of autophagic protein expression scores in CT and NM from patients who were dead (black bars) or patients who were survive (white bars). (C) Overall survival time for patients with high atuophagic protein expressions (blue bars) or low protein expressions (red bars) in CT or NM region. **, p < 0.01; ***, p < 0.001; NS, p > 0.05

Mentions: Beclin 1 and LC3B (Figure 2A) were moderately expressed in CT area, but expressed robustly in NM region. Conversely, Bcl-xL showed the reversed expression patterns. As expected, the correlations among these three proteins were robust in the NM region (Beclin 1 vs. LC3B, r = 0.86, p < 0.001; Beclin 1 vs. Bcl-xL, r = –0.69, p < 0.001; Bcl-xL vs. LC3B, r = –0.65, p < 0.001). However, these correlations in CT weakened (Beclin 1 vs. LC3B, r = 0.41, p < 0.01; Beclin 1 vs. Bcl-xL, r = –0.32, p < 0.01; Bcl-xL vs. LC3B, r = –0.31, p < 0.01).


Autophagy-based survival prognosis in human colorectal carcinoma.

Yang M, Zhao H, Guo L, Zhang Q, Zhao L, Bai S, Zhang M, Xu S, Wang F, Wang X, Zhao B - Oncotarget (2015)

Overall survivals and expression of three autophagic proteins in both the center of tumor (CT) area and noncancerous mucosal (NM) region(A) Representative examples of Beclin 1, LC3B and Bcl-xL immunostaining in CT (lower panel) and NM (upper panel) (magnification, X200). (B) Comparison of the mean (±SE) of autophagic protein expression scores in CT and NM from patients who were dead (black bars) or patients who were survive (white bars). (C) Overall survival time for patients with high atuophagic protein expressions (blue bars) or low protein expressions (red bars) in CT or NM region. **, p < 0.01; ***, p < 0.001; NS, p > 0.05
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4466671&req=5

Figure 2: Overall survivals and expression of three autophagic proteins in both the center of tumor (CT) area and noncancerous mucosal (NM) region(A) Representative examples of Beclin 1, LC3B and Bcl-xL immunostaining in CT (lower panel) and NM (upper panel) (magnification, X200). (B) Comparison of the mean (±SE) of autophagic protein expression scores in CT and NM from patients who were dead (black bars) or patients who were survive (white bars). (C) Overall survival time for patients with high atuophagic protein expressions (blue bars) or low protein expressions (red bars) in CT or NM region. **, p < 0.01; ***, p < 0.001; NS, p > 0.05
Mentions: Beclin 1 and LC3B (Figure 2A) were moderately expressed in CT area, but expressed robustly in NM region. Conversely, Bcl-xL showed the reversed expression patterns. As expected, the correlations among these three proteins were robust in the NM region (Beclin 1 vs. LC3B, r = 0.86, p < 0.001; Beclin 1 vs. Bcl-xL, r = –0.69, p < 0.001; Bcl-xL vs. LC3B, r = –0.65, p < 0.001). However, these correlations in CT weakened (Beclin 1 vs. LC3B, r = 0.41, p < 0.01; Beclin 1 vs. Bcl-xL, r = –0.32, p < 0.01; Bcl-xL vs. LC3B, r = –0.31, p < 0.01).

Bottom Line: We developed an autophagy signature for prognosis based on these three major autophagic proteins, further analysis suggested it was an independent prognostic biomarker and had its value even within single clinical stage.Combined TNM stage and this signature could significantly improve the accuracy of survival prognosis.Our findings suggest that autophagy plays an important role in the clinical cancer progression.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Heilongjiang, China.

ABSTRACT
The role of autophagy in cancers is controversial. Here we aim to determine the prognostic significance of autophagy in colorectal carcinoma patients, thereby allowing more rational development of therapeutic strategies. Through transmission electron microscopy, our data first demonstrated high frequency of defective mitochondria was strongly associated with poor overall survival in colorectal carcinoma. Next immunohistochemical study showed the expressions of Beclin 1, LC3B and Bcl-xL in both the center of tumor and adjacent noncancerous mucosal region were also correlated with overall survivals. We developed an autophagy signature for prognosis based on these three major autophagic proteins, further analysis suggested it was an independent prognostic biomarker and had its value even within single clinical stage. Combined TNM stage and this signature could significantly improve the accuracy of survival prognosis. To validate these immunohistochemical results, an internal testing cohort and an independent population were also included. Our findings suggest that autophagy plays an important role in the clinical cancer progression. Therefore autophagic proteins may be valuable prognostic biomarkers in the therapy of colorectal carcinoma and possibly other types of cancers.

Show MeSH
Related in: MedlinePlus