Figure 1 from Tumor-Secreted ADAMTSL4 Activates Latent TGFβ1 to Drive Cancer Cachexia

<p>Circulating ADAMTSL4 levels are elevated in cancer cachexia. <b>A</b> and <b>B,</b> Relative body weight (BW) change (% of initial BW; <b>A</b>) and plasma ADAMTSL4 protein levels measured by ELISA (<b>B</b>) in cachectic C26 tumor-bearing mice (<i>n</i> = 8), noncachectic MC38 tumor-bearing mice (<i>n</i> = 10), and PBS-injected controls (<i>n</i> = 13). <b>C</b> and <b>D,</b> Relative BW change (<b>C</b>) and plasma ADAMTSL4 levels (<b>D</b>) in cachectic <i>Apc</i>^Min/+ mice (<i>n</i> = 6) vs. wild-type (WT) littermates (<i>n</i> = 6). <b>E</b> and <b>F,</b> Relative BW change (<b>E</b>) and plasma ADAMTSL4 levels (<b>F</b>) in cachectic LLC tumor-bearing mice (<i>n</i> = 16) and PBS-injected controls (<i>n</i> = 11). <b>G,</b> Spearman correlation between plasma ADAMTSL4 levels and relative BW change across all mouse models (<i>n</i> = 70 XY pairs; pooled from <b>A–F</b>). <b>H</b> and <b>I,</b> Relative BW change (<b>H</b>) and circulating ADAMTSL4 levels (<b>I</b>; ELISA, log₁₀ scale) in noncachectic (non–cancer cachexia, <i>n</i> = 20) and cachectic (cancer cachexia, <i>n</i> = 27) patients with colorectal cancer. <b>J</b> and <b>K,</b> Spearman correlations in patients with colorectal cancer between circulating ADAMTSL4 levels and relative BW change (<b>J</b>; <i>n</i> = 47 XY pairs) or cachexia grade (<b>K</b>; <i>n</i> = 47 XY pairs). <b>L,</b> ROC analysis comparing circulating ADAMTSL4 with established cachexia-associated biomarkers in patients with colorectal cancer. <b>M</b> and <b>N</b>, Relative BW change (<b>M</b>) and circulating ADAMTSL4 protein levels (<b>N</b>) in noncachectic (<i>n</i> = 30) and cachectic (<i>n</i> = 14) patients with LUAD from the TRACERx cohort.

ADAMTSL4 was quantified by Olink proximity extension assay and is reported as NPX (log₂-scaled relative abundance units). <b>O</b> and <b>P,</b> Spearman correlations between ADAMTSL4 NPX values and relative BW change (<b>O</b>; <i>n</i> = 44 XY pairs) or cachexia grade (<b>P</b>; <i>n</i> = 44 XY pairs) in patients with LUAD. <b>Q,</b> Kaplan–Meier analysis of OS in patients with NSCLC from the TRACERx cohort stratified by high vs. low circulating ADAMTSL4 (median NPX as cutoff). <b>R,</b> Kaplan–Meier analysis of disease-free survival in patients with NSCLC from the TRACERx cohort stratified by high vs. low circulating ADAMTSL4 (median NPX as cutoff).