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: PSMA2

Gene summary for PSMA2

Gene summary.

Gene information	Species	Human
	Gene symbol	PSMA2
	Gene ID	5683
	Gene name	proteasome 20S subunit alpha 2
	Gene Alias	HC3
	Cytomap	7p14.1
	Gene Type	protein-coding
	GO ID	GO:0006508
	UniProtAcc	A0A024RA52

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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
5683	PSMA2	052099_1652-all-cells	Human	Prostate	BPH	1.49e-17	-5.32e-01	0.1038
5683	PSMA2	Dong_P1	Human	Prostate	Tumor	8.31e-29	-1.91e-01	0.035
5683	PSMA2	Dong_P3	Human	Prostate	Tumor	6.16e-23	-1.44e-01	0.0278
5683	PSMA2	Dong_P4	Human	Prostate	Tumor	6.45e-03	-8.00e-02	0.0292
5683	PSMA2	Dong_P5	Human	Prostate	Tumor	1.33e-45	-2.99e-01	0.053
5683	PSMA2	Dong_P6	Human	Prostate	Tumor	1.08e-03	-4.81e-01	0.0371
5683	PSMA2	P9	Human	Prostate	Tumor	1.91e-17	-7.81e-01	-0.0285
5683	PSMA2	GSM5353215_PA_AUG_PB_1B_S2	Human	Prostate	Tumor	2.27e-06	-8.55e-01	0.1557
5683	PSMA2	GSM5353216_PA_PB1A_Pool_1_3_S50_L002	Human	Prostate	Tumor	2.08e-05	-8.55e-01	0.159
5683	PSMA2	GSM5353217_PA_PB1A_Pool_2_S107_L004	Human	Prostate	Tumor	1.97e-02	-8.55e-01	0.156
5683	PSMA2	GSM5353218_PA_PB1B_Pool_1_2_S74_L003	Human	Prostate	Tumor	4.19e-04	-8.55e-01	0.1479
5683	PSMA2	GSM5353220_PA_PB1B_Pool_3_S51_L002	Human	Prostate	Tumor	2.08e-05	-8.55e-01	0.1531
5683	PSMA2	GSM5353221_PA_PB2A_Pool_1_3_S25_L001	Human	Prostate	Tumor	6.65e-21	-8.55e-01	0.1633
5683	PSMA2	GSM5353222_PA_PB2B_Pool_1_3_S52_L002	Human	Prostate	Tumor	3.82e-29	-8.55e-01	0.1608
5683	PSMA2	GSM5353223_PA_PB2B_Pool_2_S26_L001	Human	Prostate	Tumor	9.49e-18	-8.55e-01	0.1604
5683	PSMA2	GSM5353224_PA_PR5186_Pool_1_2_3_S27_L001	Human	Prostate	Tumor	4.42e-19	-8.55e-01	0.1621
5683	PSMA2	GSM5353225_PA_PR5196-1_Pool_1_2_3_S53_L002	Human	Prostate	Tumor	4.44e-10	-8.55e-01	0.1619
5683	PSMA2	GSM5353226_PA_PR5196-2_Pool_1_2_3_S54_L002	Human	Prostate	Tumor	2.27e-06	-8.55e-01	0.159
5683	PSMA2	GSM5353227_PA_PR5199-193K_Pool_1_2_3_S55_L002	Human	Prostate	Tumor	6.34e-22	-8.55e-01	0.1602
5683	PSMA2	GSM5353228_PA_PR5199-640K_Pool_1_3_S108_L004	Human	Prostate	Tumor	4.17e-03	-8.55e-01	0.1537

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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:001049810	Cervix	CC	proteasomal protein catabolic process	111/2311	490/18723	8.98e-11	1.58e-08	111
GO:004316110	Cervix	CC	proteasome-mediated ubiquitin-dependent protein catabolic process	91/2311	412/18723	1.65e-08	1.25e-06	91
GO:00096158	Cervix	CC	response to virus	73/2311	367/18723	2.22e-05	3.95e-04	73
GO:001049816	Endometrium	AEH	proteasomal protein catabolic process	108/2100	490/18723	2.73e-12	4.67e-10	108
GO:004316116	Endometrium	AEH	proteasome-mediated ubiquitin-dependent protein catabolic process	88/2100	412/18723	1.54e-09	1.36e-07	88
GO:00096159	Endometrium	AEH	response to virus	63/2100	367/18723	3.81e-04	4.10e-03	63
GO:001049817	Endometrium	EEC	proteasomal protein catabolic process	112/2168	490/18723	6.99e-13	1.40e-10	112
GO:004316117	Endometrium	EEC	proteasome-mediated ubiquitin-dependent protein catabolic process	92/2168	412/18723	3.01e-10	3.23e-08	92
GO:000961513	Endometrium	EEC	response to virus	66/2168	367/18723	1.78e-04	2.20e-03	66
GO:0010498111	Esophagus	ESCC	proteasomal protein catabolic process	369/8552	490/18723	1.13e-41	1.80e-38	369
GO:0043161111	Esophagus	ESCC	proteasome-mediated ubiquitin-dependent protein catabolic process	312/8552	412/18723	3.53e-36	4.48e-33	312
GO:000961518	Esophagus	ESCC	response to virus	238/8552	367/18723	6.65e-14	3.32e-12	238
GO:001049812	Liver	Cirrhotic	proteasomal protein catabolic process	216/4634	490/18723	2.52e-21	9.29e-19	216
GO:004316112	Liver	Cirrhotic	proteasome-mediated ubiquitin-dependent protein catabolic process	184/4634	412/18723	4.52e-19	8.85e-17	184
GO:00096155	Liver	Cirrhotic	response to virus	126/4634	367/18723	2.10e-05	2.77e-04	126
GO:001049822	Liver	HCC	proteasomal protein catabolic process	351/7958	490/18723	6.92e-40	1.46e-36	351
GO:004316122	Liver	HCC	proteasome-mediated ubiquitin-dependent protein catabolic process	299/7958	412/18723	7.82e-36	8.27e-33	299
GO:000961511	Liver	HCC	response to virus	210/7958	367/18723	7.32e-09	1.86e-07	210
GO:001049820	Oral cavity	OSCC	proteasomal protein catabolic process	336/7305	490/18723	5.45e-41	8.63e-38	336
GO:004316120	Oral cavity	OSCC	proteasome-mediated ubiquitin-dependent protein catabolic process	285/7305	412/18723	5.68e-36	5.99e-33	285

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0501220	Cervix	CC	Parkinson disease	102/1267	266/8465	1.81e-21	1.47e-19	8.66e-20	102
hsa0502018	Cervix	CC	Prion disease	98/1267	273/8465	2.64e-18	1.42e-16	8.42e-17	98
hsa0501018	Cervix	CC	Alzheimer disease	113/1267	384/8465	9.67e-14	3.92e-12	2.32e-12	113
hsa0501618	Cervix	CC	Huntington disease	94/1267	306/8465	8.49e-13	3.06e-11	1.81e-11	94
hsa0502218	Cervix	CC	Pathways of neurodegeneration - multiple diseases	128/1267	476/8465	2.87e-12	9.29e-11	5.50e-11	128
hsa0501418	Cervix	CC	Amyotrophic lateral sclerosis	103/1267	364/8465	1.79e-11	4.47e-10	2.64e-10	103
hsa0305014	Cervix	CC	Proteasome	16/1267	46/8465	6.69e-04	3.09e-03	1.83e-03	16
hsa0501716	Cervix	CC	Spinocerebellar ataxia	35/1267	143/8465	1.77e-03	7.21e-03	4.26e-03	35
hsa05012110	Cervix	CC	Parkinson disease	102/1267	266/8465	1.81e-21	1.47e-19	8.66e-20	102
hsa0502019	Cervix	CC	Prion disease	98/1267	273/8465	2.64e-18	1.42e-16	8.42e-17	98
hsa0501019	Cervix	CC	Alzheimer disease	113/1267	384/8465	9.67e-14	3.92e-12	2.32e-12	113
hsa0501619	Cervix	CC	Huntington disease	94/1267	306/8465	8.49e-13	3.06e-11	1.81e-11	94
hsa0502219	Cervix	CC	Pathways of neurodegeneration - multiple diseases	128/1267	476/8465	2.87e-12	9.29e-11	5.50e-11	128
hsa0501419	Cervix	CC	Amyotrophic lateral sclerosis	103/1267	364/8465	1.79e-11	4.47e-10	2.64e-10	103
hsa0305015	Cervix	CC	Proteasome	16/1267	46/8465	6.69e-04	3.09e-03	1.83e-03	16
hsa0501717	Cervix	CC	Spinocerebellar ataxia	35/1267	143/8465	1.77e-03	7.21e-03	4.26e-03	35
hsa0501226	Endometrium	AEH	Parkinson disease	115/1197	266/8465	6.24e-32	1.01e-29	7.42e-30	115
hsa0502020	Endometrium	AEH	Prion disease	110/1197	273/8465	2.39e-27	2.44e-25	1.78e-25	110
hsa0501620	Endometrium	AEH	Huntington disease	118/1197	306/8465	3.00e-27	2.44e-25	1.78e-25	118
hsa0501420	Endometrium	AEH	Amyotrophic lateral sclerosis	123/1197	364/8465	2.17e-22	7.82e-21	5.72e-21	123

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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

PSMA2

SNV

Missense_Mutation

novel

c.474G>C

p.Trp158Cys

p.W158C

P25787

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-D8-A1XW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin+cyclophosphamide

PSMA2

SNV

Missense_Mutation

novel

c.643G>A

p.Glu215Lys

p.E215K

P25787

protein_coding

tolerated(0.36)

benign(0.001)

TCGA-OL-A5DA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PSMA2

insertion

Frame_Shift_Ins

novel

c.278_279insTTACTTCACTTTTTGTGCCATTTCAGGAGGGAAA

p.Ala94TyrfsTer59

p.A94Yfs*59

P25787

protein_coding

TCGA-BH-A0AY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

PSMA2

SNV

Missense_Mutation

c.383N>A

p.Arg128His

p.R128H

P25787

protein_coding

deleterious(0.03)

benign(0.095)

TCGA-AA-3811-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

PSMA2

SNV

Missense_Mutation

novel

c.503T>G

p.Val168Gly

p.V168G

P25787

protein_coding

tolerated(0.38)

benign(0.09)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

PSMA2

SNV

Missense_Mutation

c.323C>A

p.Ala108Asp

p.A108D

P25787

protein_coding

tolerated(0.53)

benign(0.129)

TCGA-F4-6570-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

PSMA2

SNV

Missense_Mutation

novel

c.244G>A

p.Asp82Asn

p.D82N

P25787

protein_coding

deleterious(0)

probably_damaging(0.953)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

PSMA2

SNV

Missense_Mutation

novel

c.495G>T

p.Lys165Asn

p.K165N

P25787

protein_coding

deleterious(0.04)

benign(0.308)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

PSMA2

SNV

Missense_Mutation

novel

c.681N>T

p.Lys227Asn

p.K227N

P25787

protein_coding

tolerated(0.18)

possibly_damaging(0.494)

TCGA-B5-A1MR-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

PSMA2

SNV

Missense_Mutation

c.383N>A

p.Arg128His

p.R128H

P25787

protein_coding

deleterious(0.03)

benign(0.095)

TCGA-BG-A0LX-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
5683	PSMA2	DRUGGABLE GENOME, PROTEASE	inhibitor	CHEMBL3545432	IXAZOMIB CITRATE
5683	PSMA2	DRUGGABLE GENOME, PROTEASE	inhibitor	CHEMBL451887	CARFILZOMIB
5683	PSMA2	DRUGGABLE GENOME, PROTEASE		BORTEZOMIB	BORTEZOMIB	24524217
5683	PSMA2	DRUGGABLE GENOME, PROTEASE	inhibitor	BORTEZOMIB	BORTEZOMIB
5683	PSMA2	DRUGGABLE GENOME, PROTEASE		CARFILZOMIB	CARFILZOMIB	24524217
5683	PSMA2	DRUGGABLE GENOME, PROTEASE	inhibitor	CHEMBL2103884	OPROZOMIB
5683	PSMA2	DRUGGABLE GENOME, PROTEASE	inhibitor	CARFILZOMIB	CARFILZOMIB
5683	PSMA2	DRUGGABLE GENOME, PROTEASE	inhibitor	CHEMBL371405	MARIZOMIB
5683	PSMA2	DRUGGABLE GENOME, PROTEASE	inhibitor	CHEMBL325041	BORTEZOMIB

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