Parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization

Across TCGA pan-cancer cohorts, RNA activity of the Parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization pathway is associated with patient survival in 23 of 34 cancer lineages. Pathway activity is summarized from the expression of its 6 member genes.

The strongest signal is observed in small cell lung cancer (SCLC), where higher Parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization pathway activity is associated with poorer disease-free survival. In most high-consensus cancer types, elevated pathway activity shows an unfavorable survival association, although some cancer types, such as SKCM and LUAD, show the opposite pattern, with higher activity associated with better survival.

SCLC, SKCM, and LUAD 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	Median	III,IV	0.260	0.742	<.001	71	view →
SKCM	OS	Median	All	0.830	0.729	.001	69	view →
LUAD	OS	Tertile	III,IV	0.807	0.526	<.001	32	view →
HNSC	OS	Quartile	All	0.506	0.293	.004	27	view →
LUSC	DFS	Tertile	II,III,IV	0.564	0.928	.001	27	view →
ACC	OS	Tertile	II,III,IV	0.900	0.683	.009	25	view →
CHOL	OS	Median	II,III,IV	0.896	0.350	.014	25	view →
MESO	DFS	Quartile	IV	0.068	0.623	.006	24	view →
OV	DFS	Tertile	IV	0.535	0.288	.018	22	view →
READ	OS	Median	II,III,IV	0.962	0.451	.008	20	view →
DLBC	DFS	Median	All	0.606	0.920	.005	14	view →
UVM	OS	Tertile	III,IV	0.837	0.419	.034	6	view →

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

GO:0061734–SCLC (DFS)

Open the SCLC breakdown →