Fig. 3: Identification of CTSL as a dual-target for tumorigenesis and T cell-mediated muscle wasting. | Nature Communications

Fig. 3: Identification of CTSL as a dual-target for tumorigenesis and T cell-mediated muscle wasting.

From: Cathepsin L as a dual-target to mitigate muscle wasting while enhancing anti-tumor efficacy of anti-PD-L1

Fig. 3: Identification of CTSL as a dual-target for tumorigenesis and T cell-mediated muscle wasting.

A Venn diagram of genes upregulated in muscles (TA, GA) and lung tumor from TB versus CON, and genes downregulated in TA from αCD8a versus IgG groups. B PPI network of 55 overlapping DEGs from (A), highlighting Communities 1 and 2 (nodes > 5; STRING combined score > 400); KEGG pathways enriched in Community 1 (adjusted p < 0.05). C Heatmap of Community 1 genes in muscle across multiple murine cancer cachexia models (Supplementary Fig. 8C). Color shows log2-fold change (FC) in cachectic (CAC) versus control (CON) groups: red, up; blue, down; *adjusted p < 0.05; **adjusted p < 0.005. D Representative WB in tumor and GA. Gapdh (lung) and vinculin (muscle) as loading controls. Two mice per group are shown (n = 4 per group); quantification for all mice in Supplementary Fig. 9A, B. For GA, samples derive from the same experiment; different gels for Cstl, and another for vinculin, were processed in parallel. Expression changes of Ctsl and neighbors in PPI network in lung (E) and muscle (F, G); color intensity shows log2 FC; red, up; blue, down; bold edge, significant DEGs (orange, up; dark blue, down). H Correlation coefficients among indicated genes in TB versus CON lung (E). I Top five KEGG pathways for upregulated Ctsl neighbors in the PPI network (F). J Top five KEGG pathways for downregulated Ctsl neighbors in PPI network (G). K Kaplan–Meier plot of TCGA LUAD patients stratified by CTSL expression (high, red, n = 254; low, black, n = 288). Correlation of CTSL versus CD274 expression in TCAG LUAD (L, n = 541; log2(TPM + 1)) and GSE283829 NSCLC (M, n = 27; log2(read count+1)). N CTSL mRNA expression in skeletal muscle of NSCLC cachexia patients (CAC) versus healthy controls (CON); E-MTAB-12781; n = 5. Box plots show median (center line), interquartile range (IQR), and whiskers to 1.5× IQR. For B, F, G, I, and J, hypergeometric test with Benjamini–Hochberg correction; for C, Wald test with Benjamini–Hochberg correction; for K, log-rank test; for L and M, two-sided t-test for Pearson correlation; for N, one-sided unpaired t-test. Source data are provided as a Source Data file.

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