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Shows the recovery experiment. Figure legend in the end the "Supplementary data. Appendix 2. Assay validation" file

This text file describes how the assay was validated

Shows the result of the linearity experiment. Figure legend in the end the "Supplementary data. Appendix 2. Assay validation" file

Members of The Danish Collaborative Research Group on Colorectal Cancer

Shows a standard curve. Figure legend in the end the "Supplementary data. Appendix 2. Assay validation" file

A text document describing how we corrected for batch variation.

Shows the result of the immunoreactivity experiment. Figure legend in the end the "Supplementary data. Appendix 2. Assay validation" file

Shows the pooled standard curves for the two batches. Figure legend in the end the "Supplementary data. Appendix 3. Adjusting for batch variation" file.

Purpose: To investigate the prognostic and predictive biomarker value of type IV collagen in colorectal cancer.Experimental Design: Retrospective evaluation of two independent cohorts of patients with colorectal cancer included prospectively in 2004–2005 (training set) and 2006–2008 (validation set). Plasma samples were available from 297 (training set) and 482 (validation set) patients. Type IV collagen determinations were performed using an ELISA. From the training set, 222 tumors were available for IHC. Clinical and follow-up data were retrieved from patient files and national registries.Results: High levels of type IV collagen showed independent prognostic significance in both cohorts with hazard ratios (HRs; for a one-unit change on the log base 2 scale) of 2.25 [95% confidence intervals (CIs), 1.78–2.84; P < 0.0001] and 2.24 (95% CI, 1.75–2.86; P < 0.0001) for the training and validation set, respectively. The prognostic impact was present both in patients with metastatic and nonmetastatic disease. The predictive value of the marker was investigated in stage II and III patients. In the training set, type IV collagen was prognostic both in the subsets of patients receiving and not receiving adjuvant antineoplastic therapy. However, in the validation set, the prognostic effect of the marker vanished when looking at patients who received adjuvant antineoplatic therapy (HR 0.90; 95% CI, 0.42–1.93) but was still present in the group not receiving adjuvant chemotherapy (HR 2.88; 95% CI, 1.98–4.21).Conclusions: The results indicate clinical validity of type IV collagen as a prognostic biomarker in colorectal cancer, although the suggested predictive role of the marker should be validated. Clin Cancer Res; 22(10); 2427–34. ©2015 AACR.

Legends for 8 supplementary figures

The liver is host to many metastatic cancers, particularly colorectal cancer, for which the last 2 decades have seen major advances in diagnosis and treatment. The liver is a vital organ, and the extent of its involvement with metastatic disease is a major determinant of survival. Metastatic cells arriving in the liver via the bloodstream encounter the microenvironment of the hepatic sinusoid. The interactions of the tumor cells with hepatic sinusoidal and extrasinusoidal cells (endothelial, Kupffer, stellate, and inflammatory cells) determine their fate. The sinusoidal cells can have a dual role, sometimes fatal to the tumor cells but also facilitatory to their survival and growth. Adhesion molecules participate in these interactions and may affect their outcome. Bone marrow–derived cells and chemokines also play a part in the early battle for survival of the metastases. Once the tumor cells have arrested and survived the initial onslaught, tumors can grow within the liver in 3 distinct patterns, reflecting differing host responses, mechanisms of vascularization, and proteolytic activity. This review aims to present current knowledge of the interactions between the host liver cells and the invading metastases that has implications for the clinical course of the disease and the response to treatment. Cancer Res; 73(7); 2031–43. ©2013 AACR.

Supplementary Table 1. List of antibodies and conditions. Supplementary Table 2. List of qPCR primers. Supplementary Table 3. Oligonucleotide sequences

PDF file 71K, Incidence of liver metastases in 10 common solid cancers based on findings at autopsy with references

Supplementary Fig 1. Identification of hepatic cells that express TNFR2. Supplementary Fig 2. Loss of TNFR2 expression does not affect the induction of CAM expression on LSEC. Supplementary Fig 3. Additional characterization of MDSC isolated from wild type and TNFR2-/- mice. Supplementary Fig 4. The recruitment of Treg cells to the liver is not reduced in TNFR1-/- mice. Supplementary Fig 5. TNFR2 expression is not required for tumor or TNF-α - induced upregulation of hepatic CXCR2 chemokines. Supplementary Fig 6. Loss of TNFR2 does not affect the expression of CXCR1 and CXCR2 on MDSC. Supplementary Fig 7. Reduced TNFR2 expression in the livers of mice treated with TNFR2 ASO. Supplementary Fig 8. HLA-DR is widely expressed in the normal liver.