The Activation of Prothrombin Seems to Play an Earlier Role than the Complement System in the Progression of Colorectal Cancer: A Mass Spectrometry Evaluation.

Maider Beitia,Paolo Romano,Marcello Ceppi,Gianluca Damonte,Aldo Profumo,Annalisa Salis,Gorka Larrinaga,Jon Danel Solano-Iturri,Marco Bruzzone

doi:10.3390/diagnostics10121077

Abstract

Colorectal cancer (CRC) is the second cause of death in men and the third in women. This work deals with the study of the low molecular weight protein fraction of sera from patients who underwent surgery for CRC and who were followed for several years thereafter. MALDI-TOF MS was used to identify serum peptidome profiles of healthy controls, non-metastatic CRC patients and metastatic CRC patients. A multiple regression model was applied to signals preliminarily selected by SAM analysis to take into account the age and gender differences between the groups. We found that, while a signal m/z 2021.08, corresponding to the C3f fragment of the complement system, appears significantly increased only in serum from metastatic CRC patients, a m/z 1561.72 signal, identified as a prothrombin fragment, has a significantly increased abundance in serum from non-metastatic patients as well. The findings were also validated by a bootstrap resampling procedure. The present results provide the basis for further studies on large cohorts of patients in order to confirm C3f and prothrombin as potential serum biomarkers. Thus, new and non-invasive tests might be developed to improve the classification of colorectal cancer.

Highlights

Colorectal cancer (CRC) is one of the most common cancers in the world
We initially analysed the peptidomic profile of 250 serum samples (95 metastatic CRC patients, 85 non-metastatic CRC patients and 70 healthy controls)
The results of the significant analysis of microarrays (SAM) analysis on mass spectrometry data put in evidence three signals showing statistically significant differences, which were able to distinguish between healthy volunteers and CRC patients

Summary

Introduction

Colorectal cancer (CRC) is one of the most common cancers in the world. Even if its death rate has dropped due to the screening techniques, it is still the second cause of death in men and the third in women [1]. Patients who receive an early diagnosis of CRC and quickly undergo surgery have a favourable five-year survival rate. Many CRC cases are diagnosed at a late stage with dramatic consequences on both therapy and survival rates [2,3]. Several authors have described the study of the low molecular weight fraction of human serum for diagnostic and/or prognostic purposes in several diseases, including cancer [4,5,6]. It has been proposed that the low molecular weight fraction of the serum proteome may be correlated with physio-pathological events occurring in all districts of the organism [7,8]. The possibility of evaluating changes in the serum composition associated to CRC onset and progression could be imagined as a valid alternative to the invasive colorectal biopsy for the future

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