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Identification of a prognostic signature in colorectal cancer using combinatorial algorithm-driven analysis.


ABSTRACT: Colorectal carcinoma is one of the most common types of malignancy and a leading cause of cancer-related death. Although clinicopathological parameters provide invaluable prognostic information, the accuracy of prognosis can be improved by using molecular biomarker signatures. Using a large dataset of immunohistochemistry-based biomarkers (n = 66), this study has developed an effective methodology for identifying optimal biomarker combinations as a prognostic tool. Biomarkers were screened and assigned to related subsets before being analysed using an iterative algorithm customised for evaluating combinatorial interactions between biomarkers based on their combined statistical power. A signature consisting of six biomarkers was identified as the best combination in terms of prognostic power. The combination of biomarkers (STAT1, UCP1, p-cofilin, LIMK2, FOXP3, and ICOS) was significantly associated with overall survival when computed as a linear variable (χ2  = 53.183, p < 0.001) and as a cluster variable (χ2  = 67.625, p < 0.001). This signature was also significantly independent of age, extramural vascular invasion, tumour stage, and lymph node metastasis (Wald = 32.898, p < 0.001). Assessment of the results in an external cohort showed that the signature was significantly associated with prognosis (χ2  = 14.217, p = 0.007). This study developed and optimised an innovative discovery approach which could be adapted for the discovery of biomarkers and molecular interactions in a range of biological and clinical studies. Furthermore, this study identified a protein signature that can be utilised as an independent prognostic method and for potential therapeutic interventions.

SUBMITTER: Alnabulsi A 

PROVIDER: S-EPMC8977276 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Identification of a prognostic signature in colorectal cancer using combinatorial algorithm-driven analysis.

Alnabulsi Abdo A   Wang Tiehui T   Pang Wei W   Ionescu Marius M   Craig Stephanie G SG   Humphries Matthew P MP   McCombe Kris K   Salto Tellez Manuel M   Alnabulsi Ayham A   Murray Graeme I GI  

The journal of pathology. Clinical research 20220118 3


Colorectal carcinoma is one of the most common types of malignancy and a leading cause of cancer-related death. Although clinicopathological parameters provide invaluable prognostic information, the accuracy of prognosis can be improved by using molecular biomarker signatures. Using a large dataset of immunohistochemistry-based biomarkers (n = 66), this study has developed an effective methodology for identifying optimal biomarker combinations as a prognostic tool. Biomarkers were screened and a  ...[more]

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