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: UBE2M

Gene summary for UBE2M

Gene summary.

Gene information	Species	Human
	Gene symbol	UBE2M
	Gene ID	9040
	Gene name	ubiquitin conjugating enzyme E2 M
	Gene Alias	UBC-RS2
	Cytomap	19q13.43
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	A0A024R4T4

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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
9040	UBE2M	LZE7T	Human	Esophagus	ESCC	9.95e-12	5.37e-01	0.0667
9040	UBE2M	LZE24T	Human	Esophagus	ESCC	9.50e-07	6.81e-02	0.0596
9040	UBE2M	LZE21T	Human	Esophagus	ESCC	1.75e-04	1.35e-01	0.0655
9040	UBE2M	P1T-E	Human	Esophagus	ESCC	1.55e-13	3.36e-01	0.0875
9040	UBE2M	P2T-E	Human	Esophagus	ESCC	3.30e-10	1.35e-01	0.1177
9040	UBE2M	P4T-E	Human	Esophagus	ESCC	5.38e-19	4.59e-01	0.1323
9040	UBE2M	P5T-E	Human	Esophagus	ESCC	4.35e-11	1.44e-01	0.1327
9040	UBE2M	P8T-E	Human	Esophagus	ESCC	9.58e-27	5.56e-01	0.0889
9040	UBE2M	P9T-E	Human	Esophagus	ESCC	1.15e-03	2.01e-01	0.1131
9040	UBE2M	P10T-E	Human	Esophagus	ESCC	1.05e-18	3.82e-01	0.116
9040	UBE2M	P11T-E	Human	Esophagus	ESCC	1.29e-05	2.93e-01	0.1426
9040	UBE2M	P12T-E	Human	Esophagus	ESCC	6.96e-06	1.03e-01	0.1122
9040	UBE2M	P15T-E	Human	Esophagus	ESCC	1.48e-08	6.21e-02	0.1149
9040	UBE2M	P16T-E	Human	Esophagus	ESCC	3.84e-08	1.62e-02	0.1153
9040	UBE2M	P17T-E	Human	Esophagus	ESCC	1.26e-04	2.34e-01	0.1278
9040	UBE2M	P20T-E	Human	Esophagus	ESCC	2.25e-04	6.33e-02	0.1124
9040	UBE2M	P21T-E	Human	Esophagus	ESCC	7.71e-09	1.04e-01	0.1617
9040	UBE2M	P22T-E	Human	Esophagus	ESCC	4.01e-24	2.65e-01	0.1236
9040	UBE2M	P23T-E	Human	Esophagus	ESCC	1.18e-17	5.30e-01	0.108
9040	UBE2M	P24T-E	Human	Esophagus	ESCC	6.95e-10	2.51e-01	0.1287

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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
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:190121426	Skin	cSCC	regulation of neuron death	112/4864	319/18723	1.71e-04	1.48e-03	112
GO:005140225	Skin	cSCC	neuron apoptotic process	88/4864	246/18723	4.04e-04	3.16e-03	88
GO:0043525111	Skin	cSCC	positive regulation of neuron apoptotic process	27/4864	58/18723	5.74e-04	4.18e-03	27
GO:004352319	Skin	cSCC	regulation of neuron apoptotic process	71/4864	212/18723	8.71e-03	4.01e-02	71
GO:0070997113	Thyroid	PTC	neuron death	171/5968	361/18723	4.32e-10	1.38e-08	171
GO:1901214113	Thyroid	PTC	regulation of neuron death	151/5968	319/18723	4.74e-09	1.24e-07	151
GO:1901216113	Thyroid	PTC	positive regulation of neuron death	58/5968	97/18723	1.32e-08	3.11e-07	58
GO:0051402112	Thyroid	PTC	neuron apoptotic process	118/5968	246/18723	8.99e-08	1.81e-06	118
GO:0043523110	Thyroid	PTC	regulation of neuron apoptotic process	102/5968	212/18723	5.45e-07	8.76e-06	102
GO:0043525112	Thyroid	PTC	positive regulation of neuron apoptotic process	35/5968	58/18723	7.35e-06	8.60e-05	35
GO:004511616	Thyroid	PTC	protein neddylation	13/5968	18/18723	5.21e-04	3.37e-03	13
GO:0070997210	Thyroid	ATC	neuron death	176/6293	361/18723	1.43e-09	3.57e-08	176
GO:190121629	Thyroid	ATC	positive regulation of neuron death	61/6293	97/18723	3.34e-09	7.77e-08	61
GO:190121428	Thyroid	ATC	regulation of neuron death	156/6293	319/18723	9.30e-09	1.96e-07	156
GO:005140227	Thyroid	ATC	neuron apoptotic process	120/6293	246/18723	5.41e-07	7.75e-06	120
GO:004352323	Thyroid	ATC	regulation of neuron apoptotic process	104/6293	212/18723	2.16e-06	2.58e-05	104
GO:004352524	Thyroid	ATC	positive regulation of neuron apoptotic process	37/6293	58/18723	2.46e-06	2.89e-05	37
GO:004511622	Thyroid	ATC	protein neddylation	13/6293	18/18723	9.27e-04	4.98e-03	13

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0412027	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0412036	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0412021	Liver	Cirrhotic	Ubiquitin mediated proteolysis	72/2530	142/8465	1.32e-07	1.97e-06	1.21e-06	72
hsa0412031	Liver	Cirrhotic	Ubiquitin mediated proteolysis	72/2530	142/8465	1.32e-07	1.97e-06	1.21e-06	72
hsa0412041	Liver	HCC	Ubiquitin mediated proteolysis	110/4020	142/8465	1.67e-13	3.74e-12	2.08e-12	110
hsa0412051	Liver	HCC	Ubiquitin mediated proteolysis	110/4020	142/8465	1.67e-13	3.74e-12	2.08e-12	110
hsa0412020	Oral cavity	OSCC	Ubiquitin mediated proteolysis	105/3704	142/8465	1.83e-13	4.37e-12	2.23e-12	105
hsa04120110	Oral cavity	OSCC	Ubiquitin mediated proteolysis	105/3704	142/8465	1.83e-13	4.37e-12	2.23e-12	105
hsa0412025	Oral cavity	LP	Ubiquitin mediated proteolysis	66/2418	142/8465	3.74e-06	3.46e-05	2.23e-05	66
hsa0412035	Oral cavity	LP	Ubiquitin mediated proteolysis	66/2418	142/8465	3.74e-06	3.46e-05	2.23e-05	66
hsa0412018	Prostate	BPH	Ubiquitin mediated proteolysis	61/1718	142/8465	5.50e-10	9.07e-09	5.61e-09	61
hsa0412019	Prostate	BPH	Ubiquitin mediated proteolysis	61/1718	142/8465	5.50e-10	9.07e-09	5.61e-09	61
hsa0412024	Prostate	Tumor	Ubiquitin mediated proteolysis	61/1791	142/8465	3.08e-09	5.09e-08	3.16e-08	61
hsa0412034	Prostate	Tumor	Ubiquitin mediated proteolysis	61/1791	142/8465	3.08e-09	5.09e-08	3.16e-08	61

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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

UBE2M

SNV

Missense_Mutation

novel

c.524N>G

p.Ser175Cys

p.S175C

P61081

protein_coding

deleterious(0.01)

benign(0.116)

TCGA-5L-AAT0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

UBE2M

insertion

Nonsense_Mutation

novel

c.450_451insCCAGGCTATTAAAGGGGAATGTTACTGCATG

p.Glu151ProfsTer4

p.E151Pfs*4

P61081

protein_coding

TCGA-BH-A0B1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

adriamycin

UBE2M

SNV

Missense_Mutation

novel

c.244N>A

p.Val82Met

p.V82M

P61081

protein_coding

deleterious(0.01)

probably_damaging(0.992)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

UBE2M

SNV

Missense_Mutation

novel

c.486N>C

p.Gln162His

p.Q162H

P61081

protein_coding

tolerated(0.18)

benign(0.007)

TCGA-C5-A8XH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

UBE2M

SNV

Missense_Mutation

novel

c.319N>A

p.Glu107Lys

p.E107K

P61081

protein_coding

deleterious(0)

benign(0.275)

TCGA-DG-A2KL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

UBE2M

SNV

Missense_Mutation

novel

c.521G>A

p.Gly174Asp

p.G174D

P61081

protein_coding

tolerated(0.3)

benign(0.031)

TCGA-EA-A3HS-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

UBE2M

SNV

Missense_Mutation

novel

c.481N>C

p.Glu161Gln

p.E161Q

P61081

protein_coding

tolerated(0.21)

benign(0.207)

TCGA-VS-A8EK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

UBE2M

SNV

Missense_Mutation

rs747189992

c.50N>T

p.Ala17Val

p.A17V

P61081

protein_coding

tolerated(0.1)

benign(0.003)

TCGA-AA-3492-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

UBE2M

SNV

Missense_Mutation

c.235N>G

p.Ser79Gly

p.S79G

P61081

protein_coding

deleterious(0.01)

benign(0.397)

TCGA-G4-6586-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

UBE2M

SNV

Missense_Mutation

novel

c.506G>A

p.Arg169Gln

p.R169Q

P61081

protein_coding

tolerated(0.26)

benign(0.005)

TCGA-A5-A0G2-01

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

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