Figure 1. The secretome of cachectic melanomas includes signaling factors with known roles in body wasting.

(A) PCA of human RNA-seq reads from tumor xenografts reveals substantial differences between cachectic versus non-cachectic melanomas. There are limited changes that occur in cachectic melanomas over time.

(B) Heatmap of 7,071 genes that are highly modulated in cachectic versus non-cachectic melanomas.

(C and D) Genes modulated with p < 0.05 and Log2R > 1 (C) and Log2R < −1 (D) in cachectic versus non-cachectic melanomas at 8 weeks after tumor implantation are shown.

(E and F) PCA of mouse RNA-seq reads from melanoma xenografts, indicative of host mouse cells of the stroma (microenvironment) associated with human cancer cells (E). There are progressive changes in the stroma from 2 to 8 weeks after melanoma injection, including a core set of 1,517 genes (F).

(G and H) Several categories are represented among upregulated (G) and downregulated (H) genes.

(I) Out of 2,641 secreted proteins, 1,557 are expressed by melanoma cells, 1,331 are significantly modulated (p < 0.05) in cachectic versus non-cachectic melanomas, and 810 are differentially expressed with p < 0.05 and Log2R > 1 or Log2R < −1.

(J and K) Secreted factors that are most highly upregulated (J) and downregulated (K) in cachectic versus non-cachectic melanomas. Log2R values are shown on the y axis (p < 0.05).

(L–U) Several signaling factors known to drive body wasting are significantly upregulated in cachectic versus non-cachectic melanomas, including GDF15 (L), IL1A (M), IL1B (N), IL6 (O), IL8/CXCL8 (P), LCN2 (Q), LIF (R), PTHLH (S), TGFA (T), and TGFB1 (U).

Bars represent SD; n is indicated. All comparisons are significant (p < 0.05) in cachectic versus control at 8 weeks after tumor cell injection. TPM, transcripts per million reads. See also Figure S1.