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	CCII_1	Human	Cervix	CC	4.76e-13	-7.60e-01	0.3249
4582	MUC1	Tumor	Human	Cervix	CC	1.28e-11	-1.89e-01	0.1241
4582	MUC1	sample1	Human	Cervix	CC	1.58e-06	1.60e-01	0.0959
4582	MUC1	sample3	Human	Cervix	CC	5.12e-30	3.86e-02	0.1387
4582	MUC1	H2	Human	Cervix	HSIL_HPV	2.22e-24	6.32e-01	0.0632
4582	MUC1	T1	Human	Cervix	CC	2.43e-09	5.24e-02	0.0918
4582	MUC1	T2	Human	Cervix	CC	1.25e-03	5.06e-01	0.0709
4582	MUC1	T3	Human	Cervix	CC	6.83e-28	-7.16e-03	0.1389
4582	MUC1	HTA11_2487_2000001011	Human	Colorectum	SER	2.79e-04	3.89e-01	-0.1808
4582	MUC1	HTA11_1938_2000001011	Human	Colorectum	AD	3.94e-09	5.16e-01	-0.0811
4582	MUC1	HTA11_347_2000001011	Human	Colorectum	AD	2.57e-04	2.66e-01	-0.1954
4582	MUC1	HTA11_411_2000001011	Human	Colorectum	SER	7.20e-10	1.46e+00	-0.2602
4582	MUC1	HTA11_2112_2000001011	Human	Colorectum	SER	2.75e-10	1.15e+00	-0.2196
4582	MUC1	HTA11_3361_2000001011	Human	Colorectum	AD	1.07e-16	6.43e-01	-0.1207
4582	MUC1	HTA11_696_2000001011	Human	Colorectum	AD	1.29e-38	9.60e-01	-0.1464
4582	MUC1	HTA11_866_2000001011	Human	Colorectum	AD	2.58e-25	6.00e-01	-0.1001
4582	MUC1	HTA11_1391_2000001011	Human	Colorectum	AD	1.95e-34	1.16e+00	-0.059
4582	MUC1	HTA11_2992_2000001011	Human	Colorectum	SER	4.63e-08	7.20e-01	-0.1706
4582	MUC1	HTA11_5212_2000001011	Human	Colorectum	AD	2.53e-07	7.03e-01	-0.2061
4582	MUC1	HTA11_5216_2000001011	Human	Colorectum	SER	2.41e-05	6.87e-01	-0.1462

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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:00971939	Breast	Precancer	intrinsic apoptotic signaling pathway	59/1080	288/18723	8.07e-18	3.60e-15	59
GO:20012339	Breast	Precancer	regulation of apoptotic signaling pathway	65/1080	356/18723	7.70e-17	3.17e-14	65
GO:20012429	Breast	Precancer	regulation of intrinsic apoptotic signaling pathway	41/1080	164/18723	6.48e-16	2.31e-13	41
GO:20012349	Breast	Precancer	negative regulation of apoptotic signaling pathway	39/1080	224/18723	5.35e-10	4.77e-08	39
GO:20012439	Breast	Precancer	negative regulation of intrinsic apoptotic signaling pathway	23/1080	98/18723	5.82e-09	4.45e-07	23
GO:19017969	Breast	Precancer	regulation of signal transduction by p53 class mediator	19/1080	93/18723	1.20e-06	4.60e-05	19
GO:00723319	Breast	Precancer	signal transduction by p53 class mediator	26/1080	163/18723	2.23e-06	7.76e-05	26
GO:00723328	Breast	Precancer	intrinsic apoptotic signaling pathway by p53 class mediator	16/1080	76/18723	5.49e-06	1.63e-04	16
GO:00436209	Breast	Precancer	regulation of DNA-templated transcription in response to stress	13/1080	53/18723	7.06e-06	1.95e-04	13
GO:00436189	Breast	Precancer	regulation of transcription from RNA polymerase II promoter in response to stress	12/1080	47/18723	1.02e-05	2.67e-04	12
GO:19022537	Breast	Precancer	regulation of intrinsic apoptotic signaling pathway by p53 class mediator	9/1080	29/18723	2.40e-05	5.53e-04	9
GO:00086308	Breast	Precancer	intrinsic apoptotic signaling pathway in response to DNA damage	16/1080	99/18723	1.65e-04	2.74e-03	16
GO:19021655	Breast	Precancer	regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	6/1080	16/18723	1.76e-04	2.87e-03	6
GO:00427718	Breast	Precancer	intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	9/1080	43/18723	6.51e-04	7.99e-03	9
GO:19022293	Breast	Precancer	regulation of intrinsic apoptotic signaling pathway in response to DNA damage	8/1080	36/18723	8.49e-04	9.82e-03	8
GO:20010208	Breast	Precancer	regulation of response to DNA damage stimulus	24/1080	219/18723	1.93e-03	1.87e-02	24
GO:00360037	Breast	Precancer	positive regulation of transcription from RNA polymerase II promoter in response to stress	6/1080	24/18723	1.99e-03	1.90e-02	6
GO:00303309	Breast	Precancer	DNA damage response, signal transduction by p53 class mediator	11/1080	72/18723	2.65e-03	2.36e-02	11
GO:00315714	Breast	Precancer	mitotic G1 DNA damage checkpoint	6/1080	30/18723	6.54e-03	4.51e-02	6
GO:19021661	Breast	Precancer	negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	4/1080	14/18723	6.92e-03	4.67e-02	4

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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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