Abstract
Colon cancer is an aggressive tumor form with a poor prognosis. This study reports a comparative proteomic analysis performed by using two-dimensional differential in-gel electrophoresis (2D-DIGE) between 26 pooled colon cancer surgical tissues and adjacent non-tumoral tissues, to identify potential target proteins correlated with carcinogenesis. The DAVID functional classification tool revealed that most of the differentially regulated proteins, acting both intracellularly and extracellularly, concur across multiple cancer steps. The identified protein classes include proteins involved in cell proliferation, apoptosis, metabolic pathways, oxidative stress, cell motility, Ras signal transduction, and cytoskeleton. Interestingly, networks and pathways analysis showed that the identified proteins could be biologically inter-connected to the tumor-host microenvironment, including innate immune response, platelet and neutrophil degranulation, and hemostasis. Finally, transgelin (TAGL), here identified for the first time with four different protein species, collectively down-regulated in colon cancer tissues, emerged as a top-ranked biomarker for colorectal cancer (CRC). In conclusion, our findings revealed a different proteomic profiling in colon cancer tissues characterized by the deregulation of specific pathways involved in hallmarks of cancer. All of these proteins may represent promising novel colon cancer biomarkers and potential therapeutic targets, if validated in larger cohorts of patients.
Highlights
Colorectal cancer (CRC) is an aggressive type of tumor and a leading cause of cancer death worldwide [1]
This study reports a comparative proteomic analysis performed by using two-dimensional differential in-gel electrophoresis (2D-DIGE) between 26 pooled colon cancer surgical tissues and adjacent non-tumoral tissues, to identify potential target proteins correlated with carcinogenesis
Genetic predisposition is considered an important factor in colorectal carcinogenesis, more than 80% of colorectal cancer (CRC) occurs in the absence of a family history [3,4]
Summary
Colorectal cancer (CRC) is an aggressive type of tumor and a leading cause of cancer death worldwide [1]. Genetic predisposition is considered an important factor in colorectal carcinogenesis, more than 80% of CRC occurs in the absence of a family history [3,4]. Several genes have been directly implicated in the etiology of colorectal cancer, and some tumor-intrinsic molecular mechanisms controlling colorectal carcinogenesis have been identified, novel diagnostic and prognostic tools as well as novel therapeutic strategies are still needed to prevent colon cancer progression. This scenario emphasizes the need to identify multiparametric biological markers for more accurate cancer detection and management. The underlying assumption is that the measurements recorded on the pool are equal to the average of the measurements on the individual samples
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