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Prognostic and predictive value of an autophagy-related signature for early relapse in stages I-III colon cancer.

07:00 EST 19th February 2019 | BioPortfolio

Summary of "Prognostic and predictive value of an autophagy-related signature for early relapse in stages I-III colon cancer."

We postulated that expression differences of autophagy-related genes are instrumental in stratifying the risk of early relapse after surgery and evaluating the prognosis of patients with stages I-III colon cancer. Therefore, propensity score matching analysis was performed between patients in early relapse group and long-term survival group from GSE39582 test series and internal validation series. Using Cox regression model, a nine-autophagy-related signature (CAPN2, ATG16L2, TP63, SIRT1, RPS6KB1, PEX3, ATG5, UVRAG, NAF1) was established to classify patients into those at high risk of early relapse (high-risk group), and those at low risk of early relapse (low-risk group). Relapse-free survival (RFS) was significantly different between the two groups in test [hazard ratio (HR): 2.019, 95% confidence interval (CI): 1.362-2.992, P < 0.001], internal validation (
HR:
2.464, 95%
CI:
1.196-5.079, P < 0.001) and another two external validation series (GSE14333-
HR:
2.250, 95%
CI:
1.227-4.126, P = 0.007; GSE33113-
HR:
5.552, 95%
CI:
2.098-14.693, P < 0.001). Then, based on RFS, we developed a nomogram, integrating the nine-autophagy-related classifier and four clinicopathological risk factors to evaluate prognosis of stages I-III colon cancer patients. Time-dependent receiver operating curve at 2 years showed that the integrated signature (area under curve = 0.758) had better prognostic accuracy than American Joint Committee on Cancer TNM stage (area under curve = 0.620). In conclusion, we identified and built a nine-autophagy-related signature, a credible approach to early relapse prediction in stages I-III colon cancer patients, which can assist physicians in devising more efficient therapeutic strategies.

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Journal Details

This article was published in the following journal.

Name: Carcinogenesis
ISSN: 1460-2180
Pages:

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An autophagy related protein that is similar to UBIQUITIN-ACTIVATING ENZYME E1. It functions in CYTOPLASM to VACUOLE transport (Cvt) and AUTOPHAGY by activating ATG12 PROTEIN for its conjugation with ATG5 PROTEIN, as well as the conjugation of ATG8 FAMILY PROTEINS with phosphatidylethanolamine for ATG8 association to Cvt vesicles and AUTOPHAGOSOME membranes. It is also required for the nitrogen starvation response in yeast, MITOPHAGY; and autophagic cell death induced by CASPASE 8 inhibition.

Proteins and enzymes that function, often as components of MULTIPROTEIN COMPLEXES, to assemble AUTOPHAGOSOMES and carry out AUTOPHAGY.

An autophagy-related protein that functions in AUTOPHAGOSOME biogenesis. It is conjugated to the ATG12 PROTEIN via a process that is similar to UBIQUITINATION and involves the ATG7 PROTEIN and ATG10 enzyme. The ATG12-ATG5 conjugate acts as an E3 UBIQUITIN LIGASE-like enzyme and is required for the localization of ATG8 PROTEINS to AUTOPHAGOSOME vesicle membranes and modification of membrane lipids.

A serine/threonine-protein kinase that functions in AUTOPHAGY in response to starvation. It acts on the PHOSPHATIDYLINOSITOL 3-KINASE complex PIK3C3 to regulate AUTOPHAGOSOME formation. It also functions as both a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) and is activated by AMPK, which it also negatively regulates.

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