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: PSME2

Gene summary for PSME2

Gene summary.

Gene information	Species	Human
	Gene symbol	PSME2
	Gene ID	5721
	Gene name	proteasome activator subunit 2
	Gene Alias	PA28B
	Cytomap	14q12
	Gene Type	protein-coding
	GO ID	GO:0000082
	UniProtAcc	Q86SZ7

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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
5721	PSME2	GSM4909282	Human	Breast	IDC	1.98e-07	3.82e-01	-0.0288
5721	PSME2	GSM4909286	Human	Breast	IDC	4.16e-13	-4.42e-01	0.1081
5721	PSME2	GSM4909287	Human	Breast	IDC	2.86e-04	3.44e-01	0.2057
5721	PSME2	GSM4909288	Human	Breast	IDC	3.48e-03	1.69e-01	0.0988
5721	PSME2	GSM4909296	Human	Breast	IDC	1.95e-09	6.50e-02	0.1524
5721	PSME2	GSM4909297	Human	Breast	IDC	3.71e-14	-1.97e-01	0.1517
5721	PSME2	GSM4909298	Human	Breast	IDC	3.51e-12	-3.88e-01	0.1551
5721	PSME2	GSM4909301	Human	Breast	IDC	3.34e-05	-2.13e-01	0.1577
5721	PSME2	GSM4909311	Human	Breast	IDC	5.81e-35	-4.32e-01	0.1534
5721	PSME2	GSM4909312	Human	Breast	IDC	3.63e-13	-3.36e-01	0.1552
5721	PSME2	GSM4909315	Human	Breast	IDC	6.83e-03	1.15e-01	0.21
5721	PSME2	GSM4909316	Human	Breast	IDC	6.55e-07	3.40e-01	0.21
5721	PSME2	GSM4909319	Human	Breast	IDC	2.71e-45	-2.59e-01	0.1563
5721	PSME2	GSM4909320	Human	Breast	IDC	1.75e-04	-2.81e-01	0.1575
5721	PSME2	GSM4909321	Human	Breast	IDC	2.63e-13	5.38e-02	0.1559
5721	PSME2	brca1	Human	Breast	Precancer	3.39e-19	6.17e-01	-0.0338
5721	PSME2	brca2	Human	Breast	Precancer	4.50e-16	5.44e-01	-0.024
5721	PSME2	brca3	Human	Breast	Precancer	3.17e-03	3.49e-01	-0.0263
5721	PSME2	NCCBC14	Human	Breast	DCIS	1.79e-10	-3.23e-01	0.2021
5721	PSME2	NCCBC2	Human	Breast	DCIS	5.74e-03	-2.52e-01	0.1554

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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
Prostate		BPH: Benign Prostatic Hyperplasia
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗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:00448439	Thyroid	PTC	cell cycle G1/S phase transition	112/5968	241/18723	1.37e-06	1.96e-05	112
GO:0010952113	Thyroid	PTC	positive regulation of peptidase activity	94/5968	197/18723	2.34e-06	3.11e-05	94
GO:19019878	Thyroid	PTC	regulation of cell cycle phase transition	167/5968	390/18723	2.97e-06	3.87e-05	167
GO:0052547113	Thyroid	PTC	regulation of peptidase activity	191/5968	461/18723	7.82e-06	9.02e-05	191
GO:0052548113	Thyroid	PTC	regulation of endopeptidase activity	174/5968	432/18723	1.20e-04	9.55e-04	174
GO:200004515	Thyroid	PTC	regulation of G1/S transition of mitotic cell cycle	66/5968	142/18723	1.86e-04	1.41e-03	66
GO:19028067	Thyroid	PTC	regulation of cell cycle G1/S phase transition	76/5968	168/18723	1.87e-04	1.41e-03	76
GO:0010950113	Thyroid	PTC	positive regulation of endopeptidase activity	80/5968	179/18723	2.09e-04	1.55e-03	80
GO:001049832	Thyroid	ATC	proteasomal protein catabolic process	309/6293	490/18723	1.78e-41	1.13e-37	309
GO:004217635	Thyroid	ATC	regulation of protein catabolic process	239/6293	391/18723	2.63e-29	1.85e-26	239
GO:190336235	Thyroid	ATC	regulation of cellular protein catabolic process	168/6293	255/18723	3.50e-26	1.58e-23	168
GO:190305035	Thyroid	ATC	regulation of proteolysis involved in cellular protein catabolic process	146/6293	221/18723	4.18e-23	1.20e-20	146
GO:006113633	Thyroid	ATC	regulation of proteasomal protein catabolic process	128/6293	187/18723	1.63e-22	4.30e-20	128
GO:004586234	Thyroid	ATC	positive regulation of proteolysis	202/6293	372/18723	1.07e-16	9.42e-15	202
GO:004477219	Thyroid	ATC	mitotic cell cycle phase transition	223/6293	424/18723	3.46e-16	2.88e-14	223
GO:000734622	Thyroid	ATC	regulation of mitotic cell cycle	236/6293	457/18723	7.58e-16	5.92e-14	236
GO:190199015	Thyroid	ATC	regulation of mitotic cell cycle phase transition	156/6293	299/18723	2.19e-11	7.80e-10	156
GO:190198715	Thyroid	ATC	regulation of cell cycle phase transition	187/6293	390/18723	2.36e-09	5.61e-08	187
GO:004484316	Thyroid	ATC	cell cycle G1/S phase transition	119/6293	241/18723	2.68e-07	4.10e-06	119
GO:000008216	Thyroid	ATC	G1/S transition of mitotic cell cycle	107/6293	214/18723	4.83e-07	6.99e-06	107

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0305010	Breast	Precancer	Proteasome	25/684	46/8465	4.35e-16	9.81e-15	7.52e-15	25
hsa0461218	Breast	Precancer	Antigen processing and presentation	19/684	78/8465	9.61e-06	1.12e-04	8.62e-05	19
hsa0305013	Breast	Precancer	Proteasome	25/684	46/8465	4.35e-16	9.81e-15	7.52e-15	25
hsa0461219	Breast	Precancer	Antigen processing and presentation	19/684	78/8465	9.61e-06	1.12e-04	8.62e-05	19
hsa0305023	Breast	IDC	Proteasome	26/867	46/8465	9.89e-15	2.47e-13	1.85e-13	26
hsa0461223	Breast	IDC	Antigen processing and presentation	24/867	78/8465	4.61e-07	8.33e-06	6.23e-06	24
hsa0305033	Breast	IDC	Proteasome	26/867	46/8465	9.89e-15	2.47e-13	1.85e-13	26
hsa0461233	Breast	IDC	Antigen processing and presentation	24/867	78/8465	4.61e-07	8.33e-06	6.23e-06	24
hsa0305042	Breast	DCIS	Proteasome	26/846	46/8465	5.46e-15	1.36e-13	9.99e-14	26
hsa0461242	Breast	DCIS	Antigen processing and presentation	25/846	78/8465	6.75e-08	1.28e-06	9.45e-07	25
hsa0305052	Breast	DCIS	Proteasome	26/846	46/8465	5.46e-15	1.36e-13	9.99e-14	26
hsa0461252	Breast	DCIS	Antigen processing and presentation	25/846	78/8465	6.75e-08	1.28e-06	9.45e-07	25
hsa0461220	Cervix	CC	Antigen processing and presentation	34/1267	78/8465	1.06e-09	2.14e-08	1.26e-08	34
hsa0305014	Cervix	CC	Proteasome	16/1267	46/8465	6.69e-04	3.09e-03	1.83e-03	16
hsa04612110	Cervix	CC	Antigen processing and presentation	34/1267	78/8465	1.06e-09	2.14e-08	1.26e-08	34
hsa0305015	Cervix	CC	Proteasome	16/1267	46/8465	6.69e-04	3.09e-03	1.83e-03	16
hsa0461243	Cervix	N_HPV	Antigen processing and presentation	20/349	78/8465	2.61e-11	1.42e-09	1.11e-09	20
hsa0461253	Cervix	N_HPV	Antigen processing and presentation	20/349	78/8465	2.61e-11	1.42e-09	1.11e-09	20
hsa03050	Colorectum	AD	Proteasome	29/2092	46/8465	3.87e-08	6.18e-07	3.94e-07	29
hsa030501	Colorectum	AD	Proteasome	29/2092	46/8465	3.87e-08	6.18e-07	3.94e-07	29

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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

PSME2

SNV

Missense_Mutation

novel

c.512N>A

p.Arg171His

p.R171H

Q9UL46

protein_coding

tolerated(0.06)

benign(0.36)

TCGA-AO-A0J3-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cyclophosphamide

PSME2

insertion

Nonsense_Mutation

novel

c.98_99insTCGTGATTCTATCAGTTACCTAGCTGGTAGCCTTAAGTAAGT

p.Arg34_Phe35insAspSerIleSerTyrLeuAlaGlySerLeuLysTerValArg

p.R34_F35insDSISYLAGSLK*VR

Q9UL46

protein_coding

TCGA-A2-A0ER-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

PSME2

SNV

Missense_Mutation

novel

c.229G>A

p.Glu77Lys

p.E77K

Q9UL46

protein_coding

tolerated(0.78)

benign(0.059)

TCGA-VS-A958-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PSME2

SNV

Missense_Mutation

rs150829665

c.511C>T

p.Arg171Cys

p.R171C

Q9UL46

protein_coding

deleterious(0)

possibly_damaging(0.673)

TCGA-A6-3809-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

PSME2

SNV

Missense_Mutation

c.105C>A

p.Phe35Leu

p.F35L

Q9UL46

protein_coding

deleterious(0.04)

possibly_damaging(0.577)

TCGA-AP-A056-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PSME2

SNV

Missense_Mutation

novel

c.631N>A

p.Ala211Thr

p.A211T

Q9UL46

protein_coding

tolerated(0.18)

benign(0.001)

TCGA-AX-A06F-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

PSME2

SNV

Missense_Mutation

novel

c.358N>A

p.Leu120Met

p.L120M

Q9UL46

protein_coding

tolerated(0.11)

probably_damaging(0.981)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

PSME2

SNV

Missense_Mutation

rs1136581

c.181N>T

p.Arg61Trp

p.R61W

Q9UL46

protein_coding

deleterious(0)

probably_damaging(0.91)

TCGA-AX-A3G8-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

PSME2

SNV

Missense_Mutation

c.101G>T

p.Arg34Ile

p.R34I

Q9UL46

protein_coding

tolerated(0.11)

benign(0.029)

TCGA-B5-A0JY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

PSME2

SNV

Missense_Mutation

novel

c.557N>G

p.Asp186Gly

p.D186G

Q9UL46

protein_coding

deleterious(0)

possibly_damaging(0.899)

TCGA-B5-A3FA-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

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
5721	PSME2	NA	inhibitor	CARFILZOMIB	CARFILZOMIB
5721	PSME2	NA	inhibitor	BORTEZOMIB	BORTEZOMIB

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