Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: PSMD10

Gene summary for PSMD10

Gene summary.

Gene information	Species	Human
	Gene symbol	PSMD10
	Gene ID	5716
	Gene name	proteasome 26S subunit, non-ATPase 10
	Gene Alias	dJ889N15.2
	Cytomap	Xq22.3
	Gene Type	protein-coding
	GO ID	GO:0000079
	UniProtAcc	O75832

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Malignant transformation analysis

Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
5716	PSMD10	P19T-E	Human	Esophagus	ESCC	5.68e-05	6.75e-01	0.1662
5716	PSMD10	P20T-E	Human	Esophagus	ESCC	1.22e-22	6.24e-01	0.1124
5716	PSMD10	P21T-E	Human	Esophagus	ESCC	8.00e-27	5.86e-01	0.1617
5716	PSMD10	P22T-E	Human	Esophagus	ESCC	5.62e-61	1.09e+00	0.1236
5716	PSMD10	P23T-E	Human	Esophagus	ESCC	4.33e-36	9.99e-01	0.108
5716	PSMD10	P24T-E	Human	Esophagus	ESCC	4.74e-22	5.15e-01	0.1287
5716	PSMD10	P26T-E	Human	Esophagus	ESCC	3.30e-57	1.01e+00	0.1276
5716	PSMD10	P27T-E	Human	Esophagus	ESCC	1.55e-15	3.38e-01	0.1055
5716	PSMD10	P28T-E	Human	Esophagus	ESCC	2.99e-18	3.40e-01	0.1149
5716	PSMD10	P30T-E	Human	Esophagus	ESCC	1.83e-20	5.35e-01	0.137
5716	PSMD10	P31T-E	Human	Esophagus	ESCC	1.53e-29	6.72e-01	0.1251
5716	PSMD10	P32T-E	Human	Esophagus	ESCC	1.16e-41	8.23e-01	0.1666
5716	PSMD10	P36T-E	Human	Esophagus	ESCC	1.02e-14	5.87e-01	0.1187
5716	PSMD10	P37T-E	Human	Esophagus	ESCC	3.35e-20	5.75e-01	0.1371
5716	PSMD10	P38T-E	Human	Esophagus	ESCC	3.12e-03	3.33e-01	0.127
5716	PSMD10	P39T-E	Human	Esophagus	ESCC	6.20e-16	3.90e-01	0.0894
5716	PSMD10	P40T-E	Human	Esophagus	ESCC	1.04e-15	4.77e-01	0.109
5716	PSMD10	P42T-E	Human	Esophagus	ESCC	2.23e-19	3.48e-01	0.1175
5716	PSMD10	P44T-E	Human	Esophagus	ESCC	1.59e-11	3.86e-01	0.1096
5716	PSMD10	P47T-E	Human	Esophagus	ESCC	5.59e-29	5.89e-01	0.1067

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ

∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:004217627	Esophagus	HGIN	regulation of protein catabolic process	119/2587	391/18723	8.09e-18	2.43e-15	119
GO:001049826	Esophagus	HGIN	proteasomal protein catabolic process	139/2587	490/18723	1.20e-17	3.41e-15	139
GO:004586227	Esophagus	HGIN	positive regulation of proteolysis	107/2587	372/18723	2.61e-14	4.60e-12	107
GO:004316126	Esophagus	HGIN	proteasome-mediated ubiquitin-dependent protein catabolic process	114/2587	412/18723	7.00e-14	1.20e-11	114
GO:190336227	Esophagus	HGIN	regulation of cellular protein catabolic process	81/2587	255/18723	1.16e-13	1.93e-11	81
GO:190332027	Esophagus	HGIN	regulation of protein modification by small protein conjugation or removal	78/2587	242/18723	1.40e-13	2.26e-11	78
GO:000989626	Esophagus	HGIN	positive regulation of catabolic process	126/2587	492/18723	1.46e-12	2.09e-10	126
GO:003133126	Esophagus	HGIN	positive regulation of cellular catabolic process	112/2587	427/18723	5.15e-12	6.72e-10	112
GO:190305027	Esophagus	HGIN	regulation of proteolysis involved in cellular protein catabolic process	70/2587	221/18723	6.21e-12	7.76e-10	70
GO:200123327	Esophagus	HGIN	regulation of apoptotic signaling pathway	97/2587	356/18723	1.36e-11	1.57e-09	97
GO:006113627	Esophagus	HGIN	regulation of proteasomal protein catabolic process	60/2587	187/18723	1.10e-10	1.12e-08	60
GO:004573227	Esophagus	HGIN	positive regulation of protein catabolic process	69/2587	231/18723	1.66e-10	1.64e-08	69
GO:003139627	Esophagus	HGIN	regulation of protein ubiquitination	64/2587	210/18723	3.02e-10	2.71e-08	64
GO:200005827	Esophagus	HGIN	regulation of ubiquitin-dependent protein catabolic process	53/2587	164/18723	9.89e-10	8.13e-08	53
GO:190336427	Esophagus	HGIN	positive regulation of cellular protein catabolic process	51/2587	155/18723	1.01e-09	8.15e-08	51
GO:190180020	Esophagus	HGIN	positive regulation of proteasomal protein catabolic process	41/2587	114/18723	2.25e-09	1.67e-07	41
GO:190305219	Esophagus	HGIN	positive regulation of proteolysis involved in cellular protein catabolic process	45/2587	133/18723	3.55e-09	2.53e-07	45
GO:003243427	Esophagus	HGIN	regulation of proteasomal ubiquitin-dependent protein catabolic process	45/2587	134/18723	4.64e-09	3.12e-07	45
GO:007233127	Esophagus	HGIN	signal transduction by p53 class mediator	49/2587	163/18723	5.71e-08	3.06e-06	49
GO:003243620	Esophagus	HGIN	positive regulation of proteasomal ubiquitin-dependent protein catabolic process	32/2587	90/18723	1.71e-07	8.47e-06	32

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.

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Somatic mutation of malignant transformation related genes

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

PSMD10

SNV

Missense_Mutation

novel

c.140N>T

p.Ala47Val

p.A47V

O75832

protein_coding

deleterious(0.02)

probably_damaging(0.983)

TCGA-AO-A1KS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

PSMD10

SNV

Missense_Mutation

c.475C>A

p.Leu159Met

p.L159M

O75832

protein_coding

deleterious(0.02)

possibly_damaging(0.887)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PSMD10

SNV

Missense_Mutation

novel

c.352N>G

p.Arg118Gly

p.R118G

O75832

protein_coding

tolerated(0.08)

benign(0.084)

TCGA-AA-3949-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

PSMD10

SNV

Missense_Mutation

novel

c.175N>G

p.Leu59Val

p.L59V

O75832

protein_coding

deleterious(0)

probably_damaging(0.978)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

PSMD10

SNV

Missense_Mutation

novel

c.671N>G

p.Val224Gly

p.V224G

O75832

protein_coding

deleterious(0.01)

benign(0.026)

TCGA-A5-A2K5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

PSMD10

SNV

Missense_Mutation

novel

c.424N>A

p.Ala142Thr

p.A142T

O75832

protein_coding

deleterious(0)

benign(0.14)

TCGA-AX-A06F-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

PSMD10

SNV

Missense_Mutation

novel

c.239N>T

p.Ala80Val

p.A80V

O75832

protein_coding

deleterious(0)

probably_damaging(0.984)

TCGA-AX-A0J1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

PSMD10

SNV

Missense_Mutation

novel

c.466N>A

p.His156Asn

p.H156N

O75832

protein_coding

tolerated(0.22)

benign(0.023)

TCGA-B5-A0JY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

PSMD10

SNV

Missense_Mutation

novel

c.657A>G

p.Ile219Met

p.I219M

O75832

protein_coding

tolerated(0.29)

benign(0.01)

TCGA-B5-A3FA-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

PSMD10

SNV

Missense_Mutation

c.462G>T

p.Met154Ile

p.M154I

O75832

protein_coding

tolerated(1)

benign(0.001)

TCGA-BS-A0UV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID	Symbol	Category	Interaction Types	Drug Claim Name	Drug Name	PMIDs
5716	PSMD10	TRANSCRIPTION FACTOR BINDING	inhibitor	BORTEZOMIB	BORTEZOMIB
5716	PSMD10	TRANSCRIPTION FACTOR BINDING	inhibitor	CARFILZOMIB	CARFILZOMIB

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