Endometrial cancer Pan-cancer protein panel Differential Abundance Analysis Results

Endometrial cancer

Endometrial cancer begins in the layer of cells that form the inner epithelial lining (endometrium) of the uterus and is sometimes referred to as uterine cancer. There is an increasing incidence worldwide, and it occurs most commonly after menopause with the majority of cases occurring between 65-75 years of age. It is the sixth most commonly occurring cancer in women. Apart from age, other risk factors include high BMI, estrogen exposure, and genetic predisposition, among others. Post-menopausal bleeding is a common symptom of endometrial cancer, and it frequently has overlapping symptoms with ovarian cancer, including pain, constipation, or diarrhea. Chemotherapy is a typical treatment option for most patients with metastatic disease. However, if endometrial cancer is discovered early it can often be cured by removing the uterus surgically (Makker V et al. (2021)) .

Differential Abundance Analysis Results

This section presents the results of the differential protein abundance analysis, visualized through a volcano plot and summarized in the accompanying table for all three comparisons: 1) disease vs. healthy samples, 2) disease vs. diseases from the same class, and 3) disease vs. all other diseases.

Disease vs Healthy

Disease vs Class

Disease vs All other

Figure 1: In the volcano plot, proteins are plotted based on their fold change (logFC) on the x-axis and the statistical significance of the change (-log10 adjusted p-value) on the y-axis. Proteins considered differentially abundant are highlighted, defined by an adjusted p-value < 0.05 and an absolute logFC > 0.5.

Table 1: The summary table lists the results for all comparisons, sorted by p-value by default. It includes key metrics such as fold change and adjusted p-value, to allow exploration of the most significant proteins for each comparison.

Protein	Description	p.adjusted	NPX fold change
HAGH	hydroxyacylglutathione hydrolase	1.2e-31	1.8
PRDX6	peroxiredoxin 6	1.1e-29	1.0
OSM	oncostatin M	9.1e-26	1.6
LTA4H	leukotriene A4 hydrolase	9.1e-26	0.8
GCG	glucagon	2.1e-21	2.1
MMP9	matrix metallopeptidase 9	3.3e-20	1.0
SORD	sorbitol dehydrogenase	9.1e-18	1.1
PPY	pancreatic polypeptide	1.5e-17	1.5
IGFBP1	insulin like growth factor binding protein 1	1.0e-16	-1.6
AGRP	agouti related neuropeptide	2.5e-16	0.9
MMP8	matrix metallopeptidase 8	2.6e-16	1.0
DEFB4B	defensin beta 4B	2.3e-15	1.8
DEFB4A	defensin beta 4A	2.3e-15	1.8
OLR1	oxidized low density lipoprotein receptor 1	8.2e-15	0.6
HGF	hepatocyte growth factor	3.4e-14	0.5
CA2	carbonic anhydrase 2	1.0e-13	1.0
ALDH1A1	aldehyde dehydrogenase 1 family member A1	1.4e-13	0.7
NXPH1	neurexophilin 1	1.8e-13	-0.5
PRDX1	peroxiredoxin 1	3.1e-13	0.7
CARHSP1	calcium regulated heat stable protein 1	1.0e-12	0.7
APLP1	amyloid beta precursor like protein 1	2.5e-12	-0.8
CKMT1B	creatine kinase, mitochondrial 1B	3.0e-12	-0.9
CKMT1A	creatine kinase, mitochondrial 1A	3.0e-12	-0.9
GUSB	glucuronidase beta	6.2e-12	0.8
PIK3AP1	phosphoinositide-3-kinase adaptor protein 1	1.1e-11	0.9
CA1	carbonic anhydrase 1	1.2e-11	0.8
NPY	neuropeptide Y	2.3e-11	0.8
HMBS	hydroxymethylbilane synthase	2.7e-11	0.6
HBQ1	hemoglobin subunit theta 1	3.0e-11	0.7
CA3	carbonic anhydrase 3	3.0e-11	0.7
BLVRB	biliverdin reductase B	4.6e-11	0.7
LHPP	phospholysine phosphohistidine inorganic pyrophosphate phosphatase	8.1e-11	0.7
PKLR	pyruvate kinase L/R	1.4e-10	0.7
ADGRG1	adhesion G protein-coupled receptor G1	5.5e-10	1.0
GHRL	ghrelin and obestatin prepropeptide	6.5e-10	-0.9
RBKS	ribokinase	8.1e-10	0.6
IRAG2	inositol 1,4,5-triphosphate receptor associated 2	9.2e-10	-1.0
PSMD9	proteasome 26S subunit, non-ATPase 9	2.8e-9	0.6
IL1RN	interleukin 1 receptor antagonist	3.3e-9	0.6
CCN1	cellular communication network factor 1	8.7e-9	0.9
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Protein	Description	p.adjusted	NPX fold change
BID	BH3 interacting domain death agonist	3.4e-8	-0.8
IGFBP2	insulin like growth factor binding protein 2	1.3e-7	-0.6
ABHD14B	abhydrolase domain containing 14B	1.2e-5	-0.6
AHCY	adenosylhomocysteinase	3.1e-5	-0.6
SDC4	syndecan 4	4.2e-5	-0.5
APP	amyloid beta precursor protein	4.2e-5	-0.5
TNFSF11	TNF superfamily member 11	4.7e-5	0.5
CA6	carbonic anhydrase 6	4.7e-5	0.5
LEP	leptin	9.9e-5	0.6
CASP8	caspase 8	1.2e-4	-0.5
S100A12	S100 calcium binding protein A12	1.7e-4	-0.6
ANGPT1	angiopoietin 1	3.8e-4	-0.6
GRPEL1	GrpE like 1, mitochondrial	4.3e-4	-0.6
DPY30	dpy-30 histone methyltransferase complex regulatory subunit	4.5e-4	-0.7
PSIP1	PC4 and SFRS1 interacting protein 1	5.0e-4	-0.7
CRACR2A	calcium release activated channel regulator 2A	7.0e-4	-0.5
ACAA1	acetyl-CoA acyltransferase 1	7.3e-4	-0.6
TIMP3	TIMP metallopeptidase inhibitor 3	9.4e-4	-0.8
MAD1L1	mitotic arrest deficient 1 like 1	1.3e-3	-0.5
SSC4D	scavenger receptor cysteine rich family member with 4 domains	3.1e-3	0.6
ALPP	alkaline phosphatase, placental	3.5e-3	0.6
IRAG2	inositol 1,4,5-triphosphate receptor associated 2	3.6e-3	-0.5
RRM2	ribonucleotide reductase regulatory subunit M2	5.5e-3	-0.5
GH1	growth hormone 1	5.5e-2	0.5
MUC16	mucin 16, cell surface associated	6.7e-2	-0.5
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Protein	Description	p.adjusted	NPX fold change
BID	BH3 interacting domain death agonist	1.0e-6	-0.9
CTSC	cathepsin C	3.1e-6	-0.5
AHCY	adenosylhomocysteinase	4.5e-6	-0.7
ACAA1	acetyl-CoA acyltransferase 1	8.2e-6	-0.8
CXCL13	C-X-C motif chemokine ligand 13	9.9e-6	-0.7
ABHD14B	abhydrolase domain containing 14B	9.9e-6	-0.7
IL1RL1	interleukin 1 receptor like 1	9.9e-6	-0.7
ALPP	alkaline phosphatase, placental	1.2e-5	0.8
VSIG4	V-set and immunoglobulin domain containing 4	1.2e-5	-0.6
VAMP5	vesicle associated membrane protein 5	1.2e-5	-0.6
HMOX2	heme oxygenase 2	1.2e-5	-0.5
SLAMF8	SLAM family member 8	1.3e-5	-0.5
IGFBP1	insulin like growth factor binding protein 1	1.7e-5	-0.9
IGFBP2	insulin like growth factor binding protein 2	1.7e-5	-0.5
CRACR2A	calcium release activated channel regulator 2A	2.0e-5	-0.7
SPARC	secreted protein acidic and cysteine rich	2.7e-5	-0.5
GHRL	ghrelin and obestatin prepropeptide	3.7e-5	-0.6
IQGAP2	IQ motif containing GTPase activating protein 2	6.5e-5	-0.5
TGM2	transglutaminase 2	7.8e-5	0.5
WASF3	WASP family member 3	8.9e-5	-0.7
IRAG2	inositol 1,4,5-triphosphate receptor associated 2	9.2e-5	-0.6
IL6	interleukin 6	9.6e-5	-1.0
TIMP3	TIMP metallopeptidase inhibitor 3	9.6e-5	-0.9
DPY30	dpy-30 histone methyltransferase complex regulatory subunit	9.6e-5	-0.7
MAD1L1	mitotic arrest deficient 1 like 1	2.1e-4	-0.6
NDUFS6	NADH:ubiquinone oxidoreductase subunit S6	2.5e-4	-0.7
BAIAP2	BAR/IMD domain containing adaptor protein 2	2.6e-4	-0.5
LBP	lipopolysaccharide binding protein	2.6e-4	-0.5
CASP8	caspase 8	2.6e-4	-0.6
SSC4D	scavenger receptor cysteine rich family member with 4 domains	2.8e-4	0.7
SRP14	signal recognition particle 14	2.8e-4	-0.5
GRPEL1	GrpE like 1, mitochondrial	4.0e-4	-0.6
CXCL11	C-X-C motif chemokine ligand 11	4.7e-4	-0.6
ANGPT1	angiopoietin 1	5.0e-4	-0.6
PTN	pleiotrophin	5.2e-4	-0.5
AHSP	alpha hemoglobin stabilizing protein	5.7e-4	0.5
S100A12	S100 calcium binding protein A12	7.1e-4	-0.5
PSIP1	PC4 and SFRS1 interacting protein 1	7.2e-4	-0.6
PLA2G2A	phospholipase A2 group IIA	7.3e-4	-0.6
ELOA	elongin A	1.2e-3	-0.5
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Pan-cancer protein panel

6 proteins have been selected by the model to predict endometrial cancer (Table 1). The two top proteins for endometrial cancer (PLAT) and (TNFSF10) are both secreted to blood and the origin of tissue expression is relatively heterogeneous, including urothelial and ductal cells, respectively. Both proteins are annotated as related to cancer by UniProt and the latter has been described to be involved in apoptosis (He W et al. (2012)). In an independent study by Enroth et al (Enroth S et al. (2018)), several proteins were upregulated, although in most cases not significant, and four of these (WFDC2, IL-10, ST2 and DKK-4) are also elevated here, although not used by the model.