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: TGFBI

Gene summary for TGFBI

Gene summary.

Gene information	Species	Human
	Gene symbol	TGFBI
	Gene ID	7045
	Gene name	transforming growth factor beta induced
	Gene Alias	BIGH3
	Cytomap	5q31.1
	Gene Type	protein-coding
	GO ID	GO:0001501
	UniProtAcc	A0A0S2Z4Q2

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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
7045	TGFBI	HTA11_3410_2000001011	Human	Colorectum	AD	1.67e-11	3.10e-01	0.0155
7045	TGFBI	HTA11_1938_2000001011	Human	Colorectum	AD	1.53e-28	1.76e+00	-0.0811
7045	TGFBI	HTA11_78_2000001011	Human	Colorectum	AD	3.21e-18	1.04e+00	-0.1088
7045	TGFBI	HTA11_696_2000001011	Human	Colorectum	AD	2.93e-09	3.35e-01	-0.1464
7045	TGFBI	HTA11_1391_2000001011	Human	Colorectum	AD	1.75e-08	3.75e-01	-0.059
7045	TGFBI	HTA11_866_3004761011	Human	Colorectum	AD	3.40e-38	9.15e-01	0.096
7045	TGFBI	HTA11_4255_2000001011	Human	Colorectum	SER	4.84e-14	1.29e+00	0.0446
7045	TGFBI	HTA11_8622_2000001021	Human	Colorectum	SER	6.39e-19	1.08e+00	0.0528
7045	TGFBI	HTA11_6801_2000001011	Human	Colorectum	SER	3.99e-03	8.04e-01	0.0171
7045	TGFBI	HTA11_10711_2000001011	Human	Colorectum	AD	1.56e-07	5.03e-01	0.0338
7045	TGFBI	HTA11_7696_3000711011	Human	Colorectum	AD	8.36e-54	1.22e+00	0.0674
7045	TGFBI	HTA11_6818_2000001021	Human	Colorectum	AD	2.97e-70	2.89e+00	0.0588
7045	TGFBI	HTA11_99999970781_79442	Human	Colorectum	MSS	3.48e-43	9.78e-01	0.294
7045	TGFBI	HTA11_99999965062_69753	Human	Colorectum	MSI-H	8.59e-16	1.81e+00	0.3487
7045	TGFBI	HTA11_99999965104_69814	Human	Colorectum	MSS	1.45e-11	5.45e-01	0.281
7045	TGFBI	HTA11_99999971662_82457	Human	Colorectum	MSS	2.12e-134	3.11e+00	0.3859
7045	TGFBI	HTA11_99999973899_84307	Human	Colorectum	MSS	5.82e-22	9.40e-01	0.2585
7045	TGFBI	HTA11_99999974143_84620	Human	Colorectum	MSS	1.07e-87	1.60e+00	0.3005
7045	TGFBI	A002-C-010	Human	Colorectum	FAP	3.30e-02	1.43e-01	0.242
7045	TGFBI	A001-C-207	Human	Colorectum	FAP	1.11e-10	5.76e-01	0.1278

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:0007162	Colorectum	SER	negative regulation of cell adhesion	68/2897	303/18723	8.02e-04	1.01e-02	68
GO:00071621	Colorectum	FAP	negative regulation of cell adhesion	61/2622	303/18723	1.96e-03	1.65e-02	61
GO:0002062	Colorectum	CRC	chondrocyte differentiation	21/2078	106/18723	5.87e-03	4.33e-02	21
GO:00071622	Colorectum	CRC	negative regulation of cell adhesion	48/2078	303/18723	7.14e-03	4.96e-02	48
GO:0061448	Endometrium	AEH	connective tissue development	44/2100	252/18723	1.92e-03	1.51e-02	44
GO:00071627	Endometrium	AEH	negative regulation of cell adhesion	49/2100	303/18723	5.43e-03	3.37e-02	49
GO:000716214	Endometrium	EEC	negative regulation of cell adhesion	54/2168	303/18723	8.19e-04	7.62e-03	54
GO:00614481	Endometrium	EEC	connective tissue development	44/2168	252/18723	3.51e-03	2.36e-02	44
GO:00301984	Esophagus	ESCC	extracellular matrix organization	171/8552	301/18723	6.08e-05	4.67e-04	171
GO:00430624	Esophagus	ESCC	extracellular structure organization	171/8552	302/18723	7.73e-05	5.76e-04	171
GO:00452294	Esophagus	ESCC	external encapsulating structure organization	172/8552	304/18723	7.80e-05	5.80e-04	172
GO:00512161	Esophagus	ESCC	cartilage development	103/8552	190/18723	1.08e-02	3.67e-02	103
GO:00020623	Esophagus	ESCC	chondrocyte differentiation	60/8552	106/18723	1.53e-02	4.94e-02	60
GO:00301983	Oral cavity	OSCC	extracellular matrix organization	146/7305	301/18723	4.67e-04	2.77e-03	146
GO:00452293	Oral cavity	OSCC	external encapsulating structure organization	147/7305	304/18723	5.30e-04	3.08e-03	147
GO:00430623	Oral cavity	OSCC	extracellular structure organization	146/7305	302/18723	5.59e-04	3.23e-03	146
GO:00071629	Oral cavity	OSCC	negative regulation of cell adhesion	145/7305	303/18723	9.95e-04	5.18e-03	145
GO:000716216	Oral cavity	EOLP	negative regulation of cell adhesion	61/2218	303/18723	2.11e-05	3.28e-04	61
GO:003019811	Oral cavity	EOLP	extracellular matrix organization	52/2218	301/18723	3.29e-03	1.90e-02	52
GO:004306211	Oral cavity	EOLP	extracellular structure organization	52/2218	302/18723	3.52e-03	2.01e-02	52

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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

TGFBI

SNV

Missense_Mutation

rs774207585

c.1831N>A

p.Glu611Lys

p.E611K

Q15582

protein_coding

tolerated(0.19)

possibly_damaging(0.565)

TCGA-A2-A0D1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

taxotere

TGFBI

SNV

Missense_Mutation

c.1414N>T

p.Leu472Phe

p.L472F

Q15582

protein_coding

deleterious(0)

possibly_damaging(0.876)

TCGA-A8-A09Q-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

TGFBI

SNV

Missense_Mutation

novel

c.1360N>G

p.Thr454Ala

p.T454A

Q15582

protein_coding

tolerated(0.89)

benign(0.001)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TGFBI

SNV

Missense_Mutation

novel

c.760N>C

p.Glu254Gln

p.E254Q

Q15582

protein_coding

tolerated(0.07)

probably_damaging(0.971)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TGFBI

SNV

Missense_Mutation

c.1071C>G

p.Ile357Met

p.I357M

Q15582

protein_coding

deleterious(0.02)

benign(0.369)

TCGA-BH-A0BZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

TGFBI

SNV

Missense_Mutation

novel

c.1483N>A

p.Asp495Asn

p.D495N

Q15582

protein_coding

tolerated(0.37)

possibly_damaging(0.811)

TCGA-C8-A12T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TGFBI

SNV

Missense_Mutation

c.358C>A

p.Leu120Met

p.L120M

Q15582

protein_coding

tolerated(0.12)

benign(0.289)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

TGFBI

SNV

Missense_Mutation

rs200065806

c.1540C>A

p.Arg514Ser

p.R514S

Q15582

protein_coding

deleterious(0.01)

possibly_damaging(0.666)

TCGA-LD-A66U-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

TGFBI

insertion

Nonsense_Mutation

novel

c.1545_1546insCTGAGATAGGGCCGTTGCACTCCAGCCTGGGCA

p.Phe515_Ser516insLeuArgTerGlyArgCysThrProAlaTrpAla

p.F515_S516insLR*GRCTPAWA

Q15582

protein_coding

TCGA-B6-A0IN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TGFBI

SNV

Missense_Mutation

novel

c.1435A>G

p.Ile479Val

p.I479V

Q15582

protein_coding

tolerated(0.23)

benign(0.208)

TCGA-2W-A8YY-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

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