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: UTRN

Gene summary for UTRN

Gene summary.

Gene information	Species	Human
	Gene symbol	UTRN
	Gene ID	7402
	Gene name	utrophin
	Gene Alias	DMDL
	Cytomap	6q24.2
	Gene Type	protein-coding
	GO ID	GO:0001952
	UniProtAcc	P46939

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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
7402	UTRN	P30T-E	Human	Esophagus	ESCC	4.00e-14	6.12e-01	0.137
7402	UTRN	P31T-E	Human	Esophagus	ESCC	5.67e-04	9.40e-02	0.1251
7402	UTRN	P32T-E	Human	Esophagus	ESCC	4.19e-04	1.59e-01	0.1666
7402	UTRN	P36T-E	Human	Esophagus	ESCC	2.10e-07	2.75e-01	0.1187
7402	UTRN	P37T-E	Human	Esophagus	ESCC	4.96e-05	1.12e-01	0.1371
7402	UTRN	P39T-E	Human	Esophagus	ESCC	2.20e-07	1.76e-01	0.0894
7402	UTRN	P40T-E	Human	Esophagus	ESCC	1.21e-07	2.92e-01	0.109
7402	UTRN	P42T-E	Human	Esophagus	ESCC	1.32e-05	3.16e-01	0.1175
7402	UTRN	P44T-E	Human	Esophagus	ESCC	2.46e-03	1.34e-01	0.1096
7402	UTRN	P47T-E	Human	Esophagus	ESCC	4.26e-05	-3.90e-02	0.1067
7402	UTRN	P48T-E	Human	Esophagus	ESCC	3.50e-06	2.64e-01	0.0959
7402	UTRN	P52T-E	Human	Esophagus	ESCC	1.29e-03	6.15e-02	0.1555
7402	UTRN	P54T-E	Human	Esophagus	ESCC	2.11e-03	1.30e-01	0.0975
7402	UTRN	P57T-E	Human	Esophagus	ESCC	4.86e-09	2.92e-01	0.0926
7402	UTRN	P61T-E	Human	Esophagus	ESCC	1.95e-12	2.90e-01	0.099
7402	UTRN	P62T-E	Human	Esophagus	ESCC	8.35e-14	9.78e-02	0.1302
7402	UTRN	P65T-E	Human	Esophagus	ESCC	1.90e-05	1.67e-01	0.0978
7402	UTRN	P74T-E	Human	Esophagus	ESCC	7.45e-08	1.70e-01	0.1479
7402	UTRN	P75T-E	Human	Esophagus	ESCC	9.85e-04	4.78e-02	0.1125
7402	UTRN	P76T-E	Human	Esophagus	ESCC	2.08e-05	1.77e-01	0.1207

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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
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:001081010	Cervix	CC	regulation of cell-substrate adhesion	69/2311	221/18723	8.57e-14	5.69e-11	69
GO:00315898	Cervix	CC	cell-substrate adhesion	96/2311	363/18723	1.48e-13	8.85e-11	96
GO:004578510	Cervix	CC	positive regulation of cell adhesion	101/2311	437/18723	1.96e-10	3.08e-08	101
GO:00019528	Cervix	CC	regulation of cell-matrix adhesion	40/2311	128/18723	1.32e-08	1.04e-06	40
GO:00071608	Cervix	CC	cell-matrix adhesion	60/2311	233/18723	1.58e-08	1.23e-06	60
GO:001081110	Cervix	CC	positive regulation of cell-substrate adhesion	34/2311	123/18723	3.66e-06	9.68e-05	34
GO:19023059	Cervix	CC	regulation of sodium ion transmembrane transport	19/2311	68/18723	4.21e-04	4.25e-03	19
GO:00020288	Cervix	CC	regulation of sodium ion transport	21/2311	90/18723	2.71e-03	1.85e-02	21
GO:00075173	Cervix	CC	muscle organ development	58/2311	327/18723	2.73e-03	1.85e-02	58
GO:00019548	Cervix	CC	positive regulation of cell-matrix adhesion	15/2311	58/18723	3.75e-03	2.38e-02	15
GO:20006498	Cervix	CC	regulation of sodium ion transmembrane transporter activity	15/2311	58/18723	3.75e-03	2.38e-02	15
GO:0010811	Colorectum	AD	positive regulation of cell-substrate adhesion	53/3918	123/18723	2.30e-08	1.27e-06	53
GO:0010810	Colorectum	AD	regulation of cell-substrate adhesion	81/3918	221/18723	4.80e-08	2.55e-06	81
GO:0031589	Colorectum	AD	cell-substrate adhesion	116/3918	363/18723	4.68e-07	1.76e-05	116
GO:0001952	Colorectum	AD	regulation of cell-matrix adhesion	50/3918	128/18723	2.05e-06	6.05e-05	50
GO:0001954	Colorectum	AD	positive regulation of cell-matrix adhesion	27/3918	58/18723	1.12e-05	2.55e-04	27
GO:0002028	Colorectum	AD	regulation of sodium ion transport	36/3918	90/18723	2.89e-05	5.37e-04	36
GO:0007160	Colorectum	AD	cell-matrix adhesion	75/3918	233/18723	3.56e-05	6.45e-04	75
GO:0045785	Colorectum	AD	positive regulation of cell adhesion	122/3918	437/18723	2.65e-04	3.28e-03	122
GO:1902305	Colorectum	AD	regulation of sodium ion transmembrane transport	27/3918	68/18723	3.19e-04	3.80e-03	27

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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

UTRN

SNV

Missense_Mutation

novel

c.8216G>C

p.Arg2739Thr

p.R2739T

P46939

protein_coding

deleterious(0)

benign(0.153)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

UTRN

SNV

Missense_Mutation

c.4951N>G

p.Gln1651Glu

p.Q1651E

P46939

protein_coding

deleterious(0.01)

probably_damaging(0.965)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

UTRN

SNV

Missense_Mutation

novel

c.2422G>C

p.Asp808His

p.D808H

P46939

protein_coding

tolerated(0.06)

benign(0.352)

TCGA-A2-A0YK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

UTRN

SNV

Missense_Mutation

c.8662G>A

p.Glu2888Lys

p.E2888K

P46939

protein_coding

deleterious(0.02)

benign(0.087)

TCGA-A2-A0YK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

UTRN

SNV

Missense_Mutation

c.2248N>G

p.Gln750Glu

p.Q750E

P46939

protein_coding

tolerated(0.09)

benign(0.034)

TCGA-A8-A07U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

UTRN

SNV

Missense_Mutation

c.5062N>C

p.Glu1688Gln

p.E1688Q

P46939

protein_coding

deleterious(0.04)

benign(0.246)

TCGA-A8-A094-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UTRN

SNV

Missense_Mutation

c.9578G>C

p.Arg3193Thr

p.R3193T

P46939

protein_coding

deleterious(0)

probably_damaging(0.955)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UTRN

SNV

Missense_Mutation

c.2587N>C

p.Ser863Pro

p.S863P

P46939

protein_coding

tolerated(0.26)

benign(0.037)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UTRN

SNV

Missense_Mutation

novel

c.8603N>C

p.Lys2868Thr

p.K2868T

P46939

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AO-A0J3-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cyclophosphamide

UTRN

SNV

Missense_Mutation

c.9787N>G

p.Leu3263Val

p.L3263V

P46939

protein_coding

deleterious(0)

probably_damaging(0.977)

TCGA-AR-A251-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

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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
7402	UTRN	NA		ENZYME INHIBITOR		15639474
7402	UTRN	NA		SMT-C1100	EZUTROMID

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