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:00000826	Oral cavity	OSCC	G1/S transition of mitotic cell cycle	120/7305	214/18723	2.86e-07	4.40e-06	120
GO:00448436	Oral cavity	OSCC	cell cycle G1/S phase transition	131/7305	241/18723	8.77e-07	1.20e-05	131
GO:20000455	Oral cavity	OSCC	regulation of G1/S transition of mitotic cell cycle	74/7305	142/18723	1.01e-03	5.24e-03	74
GO:19028064	Oral cavity	OSCC	regulation of cell cycle G1/S phase transition	84/7305	168/18723	2.38e-03	1.05e-02	84
GO:0010498110	Oral cavity	LP	proteasomal protein catabolic process	224/4623	490/18723	9.57e-25	4.00e-22	224
GO:0042176110	Oral cavity	LP	regulation of protein catabolic process	177/4623	391/18723	3.00e-19	5.87e-17	177
GO:0045862110	Oral cavity	LP	positive regulation of proteolysis	165/4623	372/18723	5.40e-17	8.46e-15	165
GO:1903362110	Oral cavity	LP	regulation of cellular protein catabolic process	119/4623	255/18723	1.52e-14	1.76e-12	119
GO:1903050110	Oral cavity	LP	regulation of proteolysis involved in cellular protein catabolic process	101/4623	221/18723	7.00e-12	5.48e-10	101
GO:0061136110	Oral cavity	LP	regulation of proteasomal protein catabolic process	89/4623	187/18723	8.05e-12	6.15e-10	89
GO:0052547110	Oral cavity	LP	regulation of peptidase activity	177/4623	461/18723	3.01e-11	2.00e-09	177
GO:0052548110	Oral cavity	LP	regulation of endopeptidase activity	164/4623	432/18723	4.33e-10	2.20e-08	164
GO:0010952110	Oral cavity	LP	positive regulation of peptidase activity	88/4623	197/18723	6.52e-10	3.14e-08	88
GO:0010950110	Oral cavity	LP	positive regulation of endopeptidase activity	79/4623	179/18723	9.34e-09	3.62e-07	79
GO:000734614	Oral cavity	LP	regulation of mitotic cell cycle	163/4623	457/18723	7.64e-08	2.56e-06	163
GO:004477215	Oral cavity	LP	mitotic cell cycle phase transition	150/4623	424/18723	4.38e-07	1.23e-05	150
GO:000008213	Oral cavity	LP	G1/S transition of mitotic cell cycle	80/4623	214/18723	2.30e-05	3.74e-04	80
GO:004484313	Oral cavity	LP	cell cycle G1/S phase transition	88/4623	241/18723	2.62e-05	4.21e-04	88
GO:190199012	Oral cavity	LP	regulation of mitotic cell cycle phase transition	104/4623	299/18723	5.34e-05	7.41e-04	104
GO:190198712	Oral cavity	LP	regulation of cell cycle phase transition	126/4623	390/18723	3.69e-04	3.64e-03	126

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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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