Padhan BMC Cancer 2016 Supplemental Results

File contains the test statistic (T) for each possible combination of 1-3 features, including the constructed features (column 5 and 6). One combination is shown per row with the name of the feature combination in the first column and the header explaining the value in each column in the first row

Raw Protein RPAs Constructed features replicate corrected

File shows the relative peak area (RPA), i.e. peak area value of the measured protein after normalization to the HSP70 level analyzed in parallel in each sample (columns 2-24, 28-42). This file contains one sample per row and one protein per column with the sample name in the first column and the protein name in the first row. Column 25-27 contain the result of the mutation analysis of KRAS and BRAF. One in column 25 (MutationKRAS) indicate that KRAS is mutated in the sample, one in column 26 (MutationBRAF) indicates that BRAF is mutated, while one in column 27 (Wildtype) indicate that neither KRAS nor BRAF is mutated. Columns 28 to 42 contain the RPA values of the constructed features, i.e. features that are calculated based on the 23 different activity levels of the 7 signal transducers in column 2-24. The four replicates of each constructed feature contains the minimum, maximum, mean, and median value based on all possible ways to combine the replicates of the proteins used to construct the feature. A one in the binary variables in column 43-46 indicate the classification of each sample as normal mucosa, colorectal cancer (CRC) stage II, CRC stage IV, or metastasis. In the last column the classification is 1 = normal mucosa, 2 = colorectal cancer (CRC) stage II, 3 = CRC stage IV, or 5 = metastasis. NaN is used to indicate that no measurement was done

Raw Protein RPAs

The relative peak area (RPA), i.e. peak area value of the 23 different activity levels of the 7 signal transducers after normalization to the HSP70 level analyzed in parallel in each sample (columns 2-24). This file contains one sample per row and one protein per column with the sample name in the first column and the protein name in the first row. Columns 25-27 contain the result of the mutation analysis of KRAS and BRAF. One in column 25 (MutationKRAS) indicate that KRAS is mutated in the sample, one in column 26 (MutationBRAF) indicates that BRAF is mutated, while one in column 27 (Wildtype) indicate that neither KRAS nor BRAF is mutated. A one in the binary variables in column 28-31 indicate the classification of each sample as normal mucosa, colorectal cancer (CRC) stage II, CRC stage IV, or metastasis. NaN is used to indicate that no measurement was done

Additional file 1: of High sensitivity isoelectric focusing to establish a signaling biomarker for the diagnosis of human colorectal cancer

Figure S1. Validation of antibodies used in the study by conventional immunoblotting. All antibodies showed immunoreactivity with the expected molecular species, in conventional immunoblotting on endothelial lysates. Figure S2. Detection of MEK1/2 protein by isoelectric focusing. There was no significant difference in MEK protein expression between normal, CRCII and CRCIV tissues. Detailed description of computational analyses; “Characterization of the data set and errors”. Figure S3. Distribution function for data subsets by Monte Carlo simulation. (DOCX 1215 kb

MOESM1 of Significant association and synergistic adverse prognostic effect of podocalyxin-like protein and epidermal growth factor receptor expression in colorectal cancer

Additional file 1. Patient and tumour characteristics in the three cohorts

MOESM2 of Significant association and synergistic adverse prognostic effect of podocalyxin-like protein and epidermal growth factor receptor expression in colorectal cancer

Additional file 2. Comparison of EGFR protein expression in CRC assessed by two different antibodies in cohort 1

S2 File -

Standard treatment for patient with peritoneal metastases from colorectal cancer is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). In recent years, the efficacy of oxaliplatin-based HIPEC has been challenged. An intensified HIPEC (oxaliplatin+irinotecan) in combination with early postoperative intraperitoneal chemotherapy (EPIC) has shown increased recurrence-free survival in retrospective studies. The aim of this trial is to develop a new HIPEC/EPIC regimen and evaluate its effect on morbidity, oncological outcome, and quality-of-life (QoL). This study is designed as a combined phase I/III multicenter randomized trial (RCT) of patients with peritoneal metastases from colorectal cancer eligible for CRS-HIPEC. An initial phase I dose escalation study, designed as a 3+3 stepwise escalation, will determine the maximum tolerable dose of 5-Fluorouracil (5-FU) as 1-day EPIC, enrolling a total of 15–30 patients in 5 dose levels. In the phase III efficacy study, patients are randomly assigned intraoperatively to either the standard treatment with oxaliplatin HIPEC (control arm) or oxaliplatin/irinotecan-HIPEC in combination with single dose of 1-day 5-FU EPIC (experimental arm). 5-FU is administered intraoperatively after CRS-HIPEC and closure of the abdomen. The primary endpoint is 12-month recurrence-free survival. Secondary endpoints include 5-year overall survival, 5-year recurrence-free survival (registry based), postoperative complications, and QoL up to 3 years after study treatment. This phase I/III trial aims to identify a more effective treatment of colorectal peritoneal metastases by combination of HIPEC and EPIC.</div

Dose escalation of 5-FU 24-hour EPIC for each titration level and concomitant treatment where irinotecan is also an investigational drug (the other drugs are non-investigational and given to both groups in the randomized part of the trial).

Dose escalation of 5-FU 24-hour EPIC for each titration level and concomitant treatment where irinotecan is also an investigational drug (the other drugs are non-investigational and given to both groups in the randomized part of the trial).</p

S3 File -

Standard treatment for patient with peritoneal metastases from colorectal cancer is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). In recent years, the efficacy of oxaliplatin-based HIPEC has been challenged. An intensified HIPEC (oxaliplatin+irinotecan) in combination with early postoperative intraperitoneal chemotherapy (EPIC) has shown increased recurrence-free survival in retrospective studies. The aim of this trial is to develop a new HIPEC/EPIC regimen and evaluate its effect on morbidity, oncological outcome, and quality-of-life (QoL). This study is designed as a combined phase I/III multicenter randomized trial (RCT) of patients with peritoneal metastases from colorectal cancer eligible for CRS-HIPEC. An initial phase I dose escalation study, designed as a 3+3 stepwise escalation, will determine the maximum tolerable dose of 5-Fluorouracil (5-FU) as 1-day EPIC, enrolling a total of 15–30 patients in 5 dose levels. In the phase III efficacy study, patients are randomly assigned intraoperatively to either the standard treatment with oxaliplatin HIPEC (control arm) or oxaliplatin/irinotecan-HIPEC in combination with single dose of 1-day 5-FU EPIC (experimental arm). 5-FU is administered intraoperatively after CRS-HIPEC and closure of the abdomen. The primary endpoint is 12-month recurrence-free survival. Secondary endpoints include 5-year overall survival, 5-year recurrence-free survival (registry based), postoperative complications, and QoL up to 3 years after study treatment. This phase I/III trial aims to identify a more effective treatment of colorectal peritoneal metastases by combination of HIPEC and EPIC.</div

S1 File -

Standard treatment for patient with peritoneal metastases from colorectal cancer is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). In recent years, the efficacy of oxaliplatin-based HIPEC has been challenged. An intensified HIPEC (oxaliplatin+irinotecan) in combination with early postoperative intraperitoneal chemotherapy (EPIC) has shown increased recurrence-free survival in retrospective studies. The aim of this trial is to develop a new HIPEC/EPIC regimen and evaluate its effect on morbidity, oncological outcome, and quality-of-life (QoL). This study is designed as a combined phase I/III multicenter randomized trial (RCT) of patients with peritoneal metastases from colorectal cancer eligible for CRS-HIPEC. An initial phase I dose escalation study, designed as a 3+3 stepwise escalation, will determine the maximum tolerable dose of 5-Fluorouracil (5-FU) as 1-day EPIC, enrolling a total of 15–30 patients in 5 dose levels. In the phase III efficacy study, patients are randomly assigned intraoperatively to either the standard treatment with oxaliplatin HIPEC (control arm) or oxaliplatin/irinotecan-HIPEC in combination with single dose of 1-day 5-FU EPIC (experimental arm). 5-FU is administered intraoperatively after CRS-HIPEC and closure of the abdomen. The primary endpoint is 12-month recurrence-free survival. Secondary endpoints include 5-year overall survival, 5-year recurrence-free survival (registry based), postoperative complications, and QoL up to 3 years after study treatment. This phase I/III trial aims to identify a more effective treatment of colorectal peritoneal metastases by combination of HIPEC and EPIC.</div