DNA methylation-dependent heterochromatin formation

Across TCGA pan-cancer cohorts, RNA activity of the DNA methylation-dependent heterochromatin formation pathway is associated with patient survival in 23 of 34 cancer lineages. Pathway activity is summarized from the expression of its 33 member genes.

The strongest signal is observed in small cell lung cancer (SCLC), where higher DNA methylation-dependent heterochromatin formation pathway activity is associated with better disease-free survival. In most high-consensus cancer types, elevated pathway activity shows an unfavorable survival association, although some cancer types, such as SCLC and HNSC, show the opposite pattern, with higher activity associated with better survival.

SCLC, HNSC, and UCS are the cancer lineages in which this pathway most reproducibly stratifies patient survival.

Pathway-activity survival associations by lineage

Ranked by sampling consensus. AUC1 and AUC2 represent the survival AUCs for the high- and low-pathway-activity groups, respectively. The group with the lower AUC is interpreted as having poorer survival. The reported p-values are derived from the log-rank test.

Lineage	Measure	Split	Stage	AUC1 high	AUC2 low	p	Sampling consensus
SCLC	DFS	Tertile	II,III,IV	0.682	0.254	<.001	66	view →
HNSC	DFS	Median	IV	0.484	0.232	<.001	54	view →
UCS	OS	Tertile	II,III,IV	0.632	0.251	.012	48	view →
BLCA	OS	Tertile	All	0.558	0.343	.002	46	view →
PAAD	DFS	Quartile	II,III,IV	0.554	0.306	.006	42	view →
READ	OS	Median	II,III,IV	0.827	0.390	<.001	36	view →
LGG	OS	Tertile	All	0.732	0.864	<.001	35	view →
UVM	DFS	Tertile	III,IV	0.244	0.791	.007	31	view →
ACC	DFS	Quartile	All	0.152	0.567	.004	21	view →
UCEC	OS	Quartile	IV	0.873	0.310	.020	16	view →
SKCM	OS	Median	All	0.820	0.734	.010	13	view →
DLBC	DFS	Tertile	All	0.566	0.912	.009	12	view →

Pink = unfavorable, green = favorable. Showing the 12 strongest of 23 lineages.

GO:0006346–SCLC (DFS)

Open the SCLC breakdown →