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: COMMD6

Gene summary for COMMD6

Gene summary.

Gene information	Species	Human
	Gene symbol	COMMD6
	Gene ID	170622
	Gene name	COMM domain containing 6
	Gene Alias	Acrg
	Cytomap	13q22.2
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	Q7Z4G1

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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
170622	COMMD6	SYSMH5	Human	Oral cavity	OSCC	3.07e-04	5.53e-01	0.0647
170622	COMMD6	SYSMH6	Human	Oral cavity	OSCC	3.65e-25	1.21e+00	0.1275
170622	COMMD6	GSM5252126_BPH283PrGF_Via	Human	Prostate	BPH	3.27e-17	5.45e-01	-0.1771
170622	COMMD6	GSM5252127_BPH283PrSF_Via	Human	Prostate	BPH	2.05e-08	4.03e-01	-0.1453
170622	COMMD6	GSM5252128_BPH327PrGF_Via	Human	Prostate	BPH	6.03e-32	9.21e-01	-0.1688
170622	COMMD6	GSM5252129_BPH327PrSF_Via	Human	Prostate	BPH	3.68e-24	7.71e-01	-0.1697
170622	COMMD6	GSM5252130_BPH340PrGF_Via	Human	Prostate	BPH	1.44e-32	8.83e-01	-0.1972
170622	COMMD6	GSM5252131_BPH340PrSF_Via	Human	Prostate	BPH	2.48e-47	1.24e+00	-0.2126
170622	COMMD6	GSM5252132_BPH389PrGF	Human	Prostate	BPH	4.33e-06	7.17e-01	-0.2247
170622	COMMD6	GSM5252133_BPH389PrSF	Human	Prostate	BPH	2.14e-05	6.20e-01	-0.2027
170622	COMMD6	GSM5252134_BPH511PrG_Fcol_3GEX	Human	Prostate	BPH	5.35e-04	2.84e-01	-0.1433
170622	COMMD6	GSM5252135_BPH511PrPUr_Fcol_3GEX	Human	Prostate	BPH	7.34e-05	2.65e-01	-0.1833
170622	COMMD6	GSM5252136_BPH556PrGA1_Fcol	Human	Prostate	BPH	8.94e-14	1.23e+00	-0.23
170622	COMMD6	GSM5252137_BPH556PrGA2_Fcol	Human	Prostate	BPH	9.56e-10	1.24e+00	-0.23
170622	COMMD6	047563_1562-all-cells	Human	Prostate	BPH	7.37e-41	-5.72e-01	0.0791
170622	COMMD6	048752_1579-all-cells	Human	Prostate	BPH	1.14e-32	-6.65e-01	0.1008
170622	COMMD6	052095_1628-all-cells	Human	Prostate	BPH	6.36e-17	-5.11e-01	0.1032
170622	COMMD6	052097_1595-all-cells	Human	Prostate	BPH	8.60e-25	-5.98e-01	0.0972
170622	COMMD6	052099_1652-all-cells	Human	Prostate	BPH	1.15e-21	-5.98e-01	0.1038
170622	COMMD6	Dong_P1	Human	Prostate	Tumor	4.37e-20	3.55e-01	0.035

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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
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:00510904	Cervix	CC	regulation of DNA-binding transcription factor activity	87/2311	440/18723	4.85e-06	1.22e-04	87
GO:005109012	Cervix	HSIL_HPV	regulation of DNA-binding transcription factor activity	35/737	440/18723	6.77e-05	1.58e-03	35
GO:0051090	Colorectum	MSS	regulation of DNA-binding transcription factor activity	106/3467	440/18723	1.88e-03	1.65e-02	106
GO:00510905	Endometrium	AEH	regulation of DNA-binding transcription factor activity	69/2100	440/18723	2.51e-03	1.87e-02	69
GO:005109013	Endometrium	EEC	regulation of DNA-binding transcription factor activity	75/2168	440/18723	3.71e-04	3.97e-03	75
GO:00510908	Esophagus	ESCC	regulation of DNA-binding transcription factor activity	252/8552	440/18723	5.22e-07	6.97e-06	252
GO:00434332	Esophagus	ESCC	negative regulation of DNA-binding transcription factor activity	103/8552	185/18723	3.86e-03	1.57e-02	103
GO:00320882	Esophagus	ESCC	negative regulation of NF-kappaB transcription factor activity	54/8552	93/18723	1.08e-02	3.67e-02	54
GO:00510902	Liver	HCC	regulation of DNA-binding transcription factor activity	220/7958	440/18723	8.04e-04	4.82e-03	220
GO:00510903	Lung	IAC	regulation of DNA-binding transcription factor activity	76/2061	440/18723	4.44e-05	1.05e-03	76
GO:005109011	Lung	AIS	regulation of DNA-binding transcription factor activity	64/1849	440/18723	1.04e-03	1.36e-02	64
GO:00510907	Oral cavity	OSCC	regulation of DNA-binding transcription factor activity	221/7305	440/18723	9.06e-07	1.23e-05	221
GO:0032088	Oral cavity	OSCC	negative regulation of NF-kappaB transcription factor activity	47/7305	93/18723	1.55e-02	4.99e-02	47
GO:005109015	Oral cavity	LP	regulation of DNA-binding transcription factor activity	147/4623	440/18723	2.00e-05	3.35e-04	147
GO:0043433	Oral cavity	LP	negative regulation of DNA-binding transcription factor activity	61/4623	185/18723	6.68e-03	3.89e-02	61
GO:005109021	Oral cavity	EOLP	regulation of DNA-binding transcription factor activity	80/2218	440/18723	5.77e-05	7.31e-04	80
GO:00320881	Oral cavity	EOLP	negative regulation of NF-kappaB transcription factor activity	22/2218	93/18723	1.05e-03	7.77e-03	22
GO:00434331	Oral cavity	EOLP	negative regulation of DNA-binding transcription factor activity	36/2218	185/18723	1.79e-03	1.17e-02	36
GO:005109031	Oral cavity	NEOLP	regulation of DNA-binding transcription factor activity	72/2005	440/18723	1.66e-04	1.84e-03	72
GO:00510906	Prostate	BPH	regulation of DNA-binding transcription factor activity	100/3107	440/18723	4.71e-04	3.37e-03	100

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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

COMMD6

SNV

Missense_Mutation

rs372073245

c.20N>T

p.Pro7Leu

p.P7L

Q7Z4G1

protein_coding

tolerated_low_confidence(0.27)

benign(0.012)

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

COMMD6

SNV

Missense_Mutation

novel

c.185N>G

p.Glu62Gly

p.E62G

Q7Z4G1

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-AJ-A3EK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

COMMD6

SNV

Missense_Mutation

novel

c.290N>T

p.Thr97Met

p.T97M

Q7Z4G1

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

COMMD6

SNV

Missense_Mutation

novel

c.280G>A

p.Val94Ile

p.V94I

Q7Z4G1

protein_coding

tolerated(0.21)

benign(0.011)

TCGA-AX-A2H2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

COMMD6

SNV

Missense_Mutation

novel

c.290N>T

p.Thr97Met

p.T97M

Q7Z4G1

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-D1-A16X-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

COMMD6

SNV

Missense_Mutation

novel

c.196C>G

p.Pro66Ala

p.P66A

Q7Z4G1

protein_coding

deleterious(0.02)

possibly_damaging(0.741)

TCGA-EY-A4KR-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

COMMD6

SNV

Missense_Mutation

rs372073245

c.20C>A

p.Pro7Gln

p.P7Q

Q7Z4G1

protein_coding

deleterious_low_confidence(0.03)

possibly_damaging(0.905)

TCGA-QS-A8F1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Chemotherapy

carboplatin

COMMD6

SNV

Missense_Mutation

c.97N>C

p.Asp33His

p.D33H

Q7Z4G1

protein_coding

deleterious(0.01)

probably_damaging(0.988)

TCGA-55-A4DF-01

Lung

lung adenocarcinoma

Male

>=65

I/II

Unknown

COMMD6

SNV

Missense_Mutation

c.113N>G

p.Leu38Arg

p.L38R

Q7Z4G1

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-BR-8680-01

Stomach

stomach adenocarcinoma

Male

<65

III/IV

Chemotherapy

oxaliplatin

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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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