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: MUC1

Gene summary for MUC1

Gene summary.

Gene information	Species	Human
	Gene symbol	MUC1
	Gene ID	4582
	Gene name	mucin 1, cell surface associated
	Gene Alias	ADMCKD
	Cytomap	1q22
	Gene Type	protein-coding
	GO ID	GO:0000075
	UniProtAcc	P15941

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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
4582	MUC1	GSM4909282	Human	Breast	IDC	4.67e-04	2.18e-01	-0.0288
4582	MUC1	GSM4909286	Human	Breast	IDC	3.04e-02	-2.40e-01	0.1081
4582	MUC1	GSM4909293	Human	Breast	IDC	6.22e-06	2.01e-01	0.1581
4582	MUC1	GSM4909296	Human	Breast	IDC	1.57e-14	4.11e-01	0.1524
4582	MUC1	GSM4909297	Human	Breast	IDC	1.06e-03	-1.51e-01	0.1517
4582	MUC1	GSM4909301	Human	Breast	IDC	2.09e-24	6.45e-01	0.1577
4582	MUC1	GSM4909302	Human	Breast	IDC	3.41e-71	1.24e+00	0.1545
4582	MUC1	GSM4909303	Human	Breast	IDC	7.59e-05	5.71e-01	0.0438
4582	MUC1	GSM4909304	Human	Breast	IDC	1.64e-29	6.40e-01	0.1636
4582	MUC1	GSM4909306	Human	Breast	IDC	1.65e-17	5.11e-01	0.1564
4582	MUC1	GSM4909307	Human	Breast	IDC	1.72e-18	5.41e-01	0.1569
4582	MUC1	GSM4909308	Human	Breast	IDC	1.51e-07	4.15e-01	0.158
4582	MUC1	GSM4909311	Human	Breast	IDC	6.70e-24	4.11e-01	0.1534
4582	MUC1	GSM4909312	Human	Breast	IDC	8.45e-17	5.14e-01	0.1552
4582	MUC1	GSM4909313	Human	Breast	IDC	4.29e-09	5.06e-01	0.0391
4582	MUC1	GSM4909315	Human	Breast	IDC	1.95e-05	3.52e-01	0.21
4582	MUC1	GSM4909317	Human	Breast	IDC	7.20e-21	7.20e-01	0.1355
4582	MUC1	GSM4909319	Human	Breast	IDC	7.20e-19	7.48e-02	0.1563
4582	MUC1	GSM4909320	Human	Breast	IDC	4.59e-04	-2.81e-01	0.1575
4582	MUC1	GSM4909321	Human	Breast	IDC	7.16e-05	2.21e-02	0.1559

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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
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
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:004361819	Prostate	Tumor	regulation of transcription from RNA polymerase II promoter in response to stress	22/3246	47/18723	2.86e-06	4.74e-05	22
GO:003033017	Prostate	Tumor	DNA damage response, signal transduction by p53 class mediator	29/3246	72/18723	3.66e-06	5.91e-05	29
GO:001820512	Prostate	Tumor	peptidyl-lysine modification	99/3246	376/18723	6.77e-06	1.02e-04	99
GO:001839411	Prostate	Tumor	peptidyl-lysine acetylation	52/3246	169/18723	1.25e-05	1.76e-04	52
GO:000716215	Prostate	Tumor	negative regulation of cell adhesion	82/3246	303/18723	1.38e-05	1.89e-04	82
GO:000008212	Prostate	Tumor	G1/S transition of mitotic cell cycle	62/3246	214/18723	1.63e-05	2.18e-04	62
GO:000647311	Prostate	Tumor	protein acetylation	59/3246	201/18723	1.68e-05	2.25e-04	59
GO:004484312	Prostate	Tumor	cell cycle G1/S phase transition	67/3246	241/18723	3.28e-05	3.88e-04	67
GO:000863017	Prostate	Tumor	intrinsic apoptotic signaling pathway in response to DNA damage	34/3246	99/18723	3.30e-05	3.89e-04	34
GO:000734613	Prostate	Tumor	regulation of mitotic cell cycle	113/3246	457/18723	3.37e-05	3.96e-04	113
GO:004477214	Prostate	Tumor	mitotic cell cycle phase transition	106/3246	424/18723	3.61e-05	4.21e-04	106
GO:004277117	Prostate	Tumor	intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	19/3246	43/18723	3.72e-05	4.33e-04	19
GO:003600316	Prostate	Tumor	positive regulation of transcription from RNA polymerase II promoter in response to stress	13/3246	24/18723	4.62e-05	5.16e-04	13
GO:200004511	Prostate	Tumor	regulation of G1/S transition of mitotic cell cycle	44/3246	142/18723	4.66e-05	5.21e-04	44
GO:003105612	Prostate	Tumor	regulation of histone modification	46/3246	152/18723	6.07e-05	6.59e-04	46
GO:190280611	Prostate	Tumor	regulation of cell cycle G1/S phase transition	49/3246	168/18723	9.98e-05	9.73e-04	49
GO:190225317	Prostate	Tumor	regulation of intrinsic apoptotic signaling pathway by p53 class mediator	14/3246	29/18723	1.22e-04	1.14e-03	14
GO:190198311	Prostate	Tumor	regulation of protein acetylation	27/3246	77/18723	1.38e-04	1.27e-03	27
GO:004277012	Prostate	Tumor	signal transduction in response to DNA damage	49/3246	172/18723	1.87e-04	1.65e-03	49
GO:200075611	Prostate	Tumor	regulation of peptidyl-lysine acetylation	23/3246	63/18723	2.14e-04	1.84e-03	23

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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

MUC1

SNV

Missense_Mutation

novel

c.640C>A

p.Pro214Thr

p.P214T

protein_coding

tolerated(0.08)

possibly_damaging(0.503)

TCGA-A7-A0DB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

MUC1

SNV

Missense_Mutation

c.1102N>T

p.Val368Phe

p.V368F

protein_coding

deleterious(0.05)

benign(0.186)

TCGA-D8-A13Z-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine

MUC1

SNV

Missense_Mutation

novel

c.998C>A

p.Thr333Asn

p.T333N

protein_coding

deleterious(0)

probably_damaging(0.923)

TCGA-D8-A1XC-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

MUC1

deletion

Frame_Shift_Del

novel

c.643_697delNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN

p.Ala215ProfsTer100

p.A215Pfs*100

protein_coding

TCGA-E2-A15S-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

MUC1

SNV

Missense_Mutation

rs759820018

c.247N>G

p.Gln83Glu

p.Q83E

protein_coding

tolerated(0.8)

benign(0.101)

TCGA-EK-A3GK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MUC1

SNV

Missense_Mutation

novel

c.620N>G

p.Ser207Cys

p.S207C

protein_coding

deleterious(0)

probably_damaging(0.968)

TCGA-HM-A3JJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MUC1

SNV

Missense_Mutation

novel

c.701N>G

p.Leu234Arg

p.L234R

protein_coding

tolerated(0.37)

benign(0.299)

TCGA-R2-A69V-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MUC1

SNV

Missense_Mutation

novel

c.1183N>A

p.Leu395Met

p.L395M

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-VS-A8EL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MUC1

SNV

Missense_Mutation

novel

c.854N>T

p.Ser285Phe

p.S285F

protein_coding

deleterious(0.03)

probably_damaging(0.999)

TCGA-VS-A94Z-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MUC1

SNV

Missense_Mutation

novel

c.175G>A

p.Glu59Lys

p.E59K

protein_coding

tolerated(0.48)

possibly_damaging(0.497)

TCGA-VS-A958-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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
4582	MUC1	CLINICALLY ACTIONABLE, ENZYME, DRUGGABLE GENOME		Anti-MUC1 mab
4582	MUC1	CLINICALLY ACTIONABLE, ENZYME, DRUGGABLE GENOME		G0-203-2c
4582	MUC1	CLINICALLY ACTIONABLE, ENZYME, DRUGGABLE GENOME		SODIUM BUTYRATE		2211839
4582	MUC1	CLINICALLY ACTIONABLE, ENZYME, DRUGGABLE GENOME		MUC-1 CART cell immunotherapy
4582	MUC1	CLINICALLY ACTIONABLE, ENZYME, DRUGGABLE GENOME		Pankomab-GEX
4582	MUC1	CLINICALLY ACTIONABLE, ENZYME, DRUGGABLE GENOME		BREVAREX MAB
4582	MUC1	CLINICALLY ACTIONABLE, ENZYME, DRUGGABLE GENOME		AS-1402	HUHMFG1
4582	MUC1	CLINICALLY ACTIONABLE, ENZYME, DRUGGABLE GENOME		SAR-566658	SAR-566658
4582	MUC1	CLINICALLY ACTIONABLE, ENZYME, DRUGGABLE GENOME		GO-203-2c	GO-203-2C
4582	MUC1	CLINICALLY ACTIONABLE, ENZYME, DRUGGABLE GENOME		AS1402	HUHMFG1

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