Kaplan-Meier curves showing the association between pretreatment plasma YKL-40 and PFS.

<p>For patients with metastatic colorectal cancer included in the NORDIC VII Study. All patients (1A), patients treated in arm A (1B), arm B (1C), and arm C (1D). Patients are dichotomized according to the age-corrected plasma YKL-40 (95 percentile level in healthy subjects). The P-value refers to the log-rank test for equality of strata.</p

Consort diagram indicating sample sizes at each stage during the study.

<p>Consort diagram indicating sample sizes at each stage during the study.</p

Demographic and Baseline Clinical Characteristics of the 510 patients with mCRC included in the Nordic VII Study with pretreatment plasma YKL-40.

<p>Demographic and Baseline Clinical Characteristics of the 510 patients with mCRC included in the Nordic VII Study with pretreatment plasma YKL-40.</p

Focused miRNA panel – miRNAs significantly associated with time to disease progression.

a<p> Interaction tests were performed for all patients and for patients with distal (sigmoid and rectum) and proximal (cecum to descending) primary tumor location, separately.</p>b<p> Hazard ratio is per inter-quartile range expression increase and is adjusted for age, sex, number of metastatic sites, prior adjuvant treatment and primary tumor location.</p>c<p> miRNA was missing in >10% of samples so interaction was not tested.</p><p>Abbreviations: HR, hazard ratio; CI, confidence interval.</p><p>Focused miRNA panel – miRNAs significantly associated with time to disease progression.</p

Focused miRNA panel – miRNAs significantly associated with overall survival.

a<p> Interaction was tested for all patients and for patients with distal (sigmoid to rectum) and proximal (cecum to descending colon) primary tumor location separately.</p>b<p> Hazard ratio is per inter-quartile range expression increase and is adjusted for age, sex, number of metastatic sites, prior adjuvant treatment and primary tumor location.</p><p>Abbreviations: HR, hazard ratio; CI, confidence interval.</p><p>Focused miRNA panel – miRNAs significantly associated with overall survival.</p

MiR-664-3p <i>in situ</i> hybridization (ISH).

<p>Panels A and B show examples of miR-664-3p ISH in infiltrating lymphocytes (A) and fibroblasts (B). Consecutive sections were stained with LNA probes against miR-664-3p, miR-126-3p and a scramble sequence. MiR-664-3p ISH signal is seen in infiltrating lymphocytes (A, arrows; B, red arrow) and in fibroblasts (B, black arrows), whereas no ISH signal is obtained with scramble probe. A strong ISH signal is seen in endothelial cells with the positive control probe miR-126-3p. The “A” in panel B indicates an artery.</p

Overall survival according to quartiles of mir-664-3p expression.

<p>Kaplan-Meier plots are shown for patients treated with CAPEOXBEV using raw (A) or mean-normalized (B) expression and patients treated with CAPEOX alone using raw (C) and mean-normalized (D) expression. Hazard ratios (HR) are unadjusted and confidence intervals (CI) are calculated using bootstrapping. The expression intervals shown in the upper right-hand corner are 40-C_t, so higher values correspond to higher expression. Black line = lowest quartile; red line = second quartile; green line = third quartile; blue line = highest quartile.</p