Additional file 1: Table S1. of Colorectal cancer health services research study protocol: the CCR-CARESS observational prospective cohort project

Grouping of complications. Table S2. Chemotherapy information at the beginning of the study. (DOCX 17 kb

Evaluation of Alpha 1-Antitrypsin and the Levels of mRNA Expression of Matrix Metalloproteinase 7, Urokinase Type Plasminogen Activator Receptor and COX-2 for the Diagnosis of Colorectal Cancer

<div><h3>Background</h3><p>Colorectal cancer (CRC) is the second most common cause of death from cancer in both men and women in the majority of developed countries. Molecular tests of blood could potentially provide this ideal screening tool.</p> <h3>Aim</h3><p>Our objective was to assess the usefulness of serum markers and mRNA expression levels in the diagnosis of CRC.</p> <h3>Methods</h3><p>In a prospective study, we measured mRNA expression levels of 13 markers (carbonic anhydrase, guanylyl cyclase C, plasminogen activator inhibitor, matrix metalloproteinase 7 (MMP7), urokinase-type plasminogen activator receptor (uPAR), urokinase-type plasminogen activator, survivin, tetranectin, vascular endothelial growth factor (VEGF), cytokeratin 20, thymidylate synthase, cyclooxygenase 2 (COX-2), and CD44) and three proteins in serum (alpha 1 antitrypsin, carcinoembryonic antigen (CEA) and activated C3 in 42 patients with CRC and 33 with normal colonoscopy results.</p> <h3>Results</h3><p>Alpha 1-antitrypsin was the serum marker that was most useful for CRC diagnosis (1.79±0.25 in the CRC group vs 1.27±0.25 in the control group, P<0.0005). The area under the ROC curve for alpha 1-antitrypsin was 0.88 (0.79–0.96). The mRNA expression levels of five markers were statistically different between CRC cases and controls: those for which the ROC area was over 75% were MMP7 (0.81) and tetranectin (0.80), COX-2 (0.78), uPAR (0.78) and carbonic anhydrase (0.77). The markers which identified early stage CRC (Stages I and II) were alpha 1-antitrypsin, uPAR, COX-2 and MMP7.</p> <h3>Conclusions</h3><p>Serum alpha 1-antitrypsin and the levels of mRNA expression of MMP7, COX-2 and uPAR have good diagnostic accuracy for CRC, even in the early stages.</p> </div

The levels of mRNA expression of the proteins analysed and the statistical significance of differences in the values between cancer tissue and healthy tissue in patients with CRC.

<p>SD; standard deviation PAI; plasminogen activator inhibitor MMP7;matrix metalloproteinase 7 uPAR; urokinase-type plasminogen activator receptor uPA;urokinase-type plasminogen activator VEGF; vascular endothelial growth factor COX-2; cyclooxygenase 2.</p

Oligonucleotide primer sequences generated used for the detection of mRNA for CRC markers.

<p>Oligonucleotide primer sequences generated used for the detection of mRNA for CRC markers.</p

ROC curves comparing carcinoembrionic antigen (CEA) in serum and MMP7 RNA expression.

<p>The areas under ROC curve for CEA and matrix metalloproteinase 7 (MMP7) were 0.84 and 0.81, respectively.</p

The areas under ROC curve for all the mRNA expression levels analysed in blood.

<p>PAI; plasminogen activator inhibitor MMP7;matrix metalloproteinase 7 uPAR; urokinase-type plasminogen activator receptor uPA;urokinase-type plasminogen activator VEGF; vascular endothelial growth factor COX-2; cyclooxygenase 2.</p

Detail of risk factors associated to two-year mortality risk categories, chemotherapy included.

<p>Risk factors include: ASA = IV, Charlson index ≥4, age>75 years, results of the surgery = R2 and Log lymph nodes ratio >-0.53.*Minor risk factor: Charlson index ≥4 and ASA = IV. †Moderate risk factors: age>75 years and Log lymph nodes ratio >-0.53. ⱡSevere risk factor: results of the surgery = R2. NA: Not applicable.</p

Descriptive sociodemographic and clinical statistics of all samples of the study.

<p>Descriptive sociodemographic and clinical statistics of all samples of the study.</p

Descriptive statistics of the adjuvant chemotherapy and molecular targeted agents employed in each sample.

<p>Descriptive statistics of the adjuvant chemotherapy and molecular targeted agents employed in each sample.</p

Categorical risk scores prediction of mortality at 1 or 2 years after surgery.

<p>Categorical risk scores prediction of mortality at 1 or 2 years after surgery.</p