Intra-patient evolution of tumor microenvironment in the pathogenesis of treatment-naïve metastatic melanoma patients

Figures & data

Table 1. Patient characteristics. Previous treatments indicate systemic therapy for metastatic disease. .

	N (9)	Patient A	Patient C	Patient D	Patient F	Patient G	Patient H	Patient I	Patient J	Patient L
Gender		Female	Male	Male	Female	Male	Male	Male	Male	Female
Age (years)	69, median	68	69	83	65	74	70	62	71	59
Breslow (mm)	4.0, median	2.5	6.0	3.4	8.7	10.0	1.8	4.0	1.4	4.1
Ulceration		–	+	+	+	+	+	–	–	–
Primary N Stage at Diagnosis		N0	N2a	N1b	N1a	N2a	N1b	N0	N0	N3a
Primary Stage at Diagnosis		IIA	IIIC	IIIC	IIIC	IVMc	IIIB	IIA	IA	IIIC
DFS (months)	33, median	7	8	36	66	0	11	36	45	33
Time between paired samples (months)	38, median	28	8	49	68	5	11	38	46	73
Mutational status		NRAS	NRAS	NRAS	BRAF V600E	NRAS	NRAS	WT	BRAF V600E	BRAF V600E
M stage		M1c	M1c	M1c	M1c	M1c	M1c	M1b	M1b	M1b
Metastatic sample, tissue of origin		Skin	Subcutaneous tissue	Duodenum	Subcutaneous tissue	Skin	Subcutaneous tissue	Subcutaneous tissue	Lung	Subcutaneous tissue
Previous treatments		None	None	None	None	None	Chemotherapy	None	None	None

CT: chemotherapy;wt: wild type; DFS: disease-free survival

Figure 1. Correlation of paired primary and metastatic tumor samples. Gene expression was assessed using the 770-gene NanoString PanCancer IO 360™ Panel. The scatter plots visualize correlation of the paired primary (x-axis) and metastatic (y-axis) melanoma patient samples. Selected genes with log₂ fold change >3 are highlighted in the plots. R denotes Pearson correlation coefficient.

Figure 2. Gene expression profiles in the primary and metastatic melanoma patient samples. (A) Unsupervised hierarchical clustering of the NanoString PanCancer IO 360™ Panel genes in paired primary (n = 9) and metastatic (n = 9) melanoma samples. The heatmap was generated using Euclidean distance with ward.D linkage. The rows in the heatmap denote genes and columns samples. The data were z-score normalized, scaled row-wise, and blue color denotes lower expression and red color higher expression. The upper panel shows annotation of the samples. (B) The heatmap visualizes differentially expressed genes between paired primary and metastatic melanoma samples (p < 0.01, moderated t-test by paired “limma” analysis). prim: primary; met: metastasis.

Data availability statement

The data supporting the findings of this study are available from the corresponding author, upon reasonable request.