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: TNC

Gene summary for TNC

Gene summary.

Gene information	Species	Human
	Gene symbol	TNC
	Gene ID	3371
	Gene name	tenascin C
	Gene Alias	150-225
	Cytomap	9q33.1
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	B4E1W8

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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
3371	TNC	LZE2T	Human	Esophagus	ESCC	5.57e-03	1.64e+00	0.082
3371	TNC	LZE4T	Human	Esophagus	ESCC	1.39e-23	2.02e+00	0.0811
3371	TNC	LZE7T	Human	Esophagus	ESCC	1.23e-02	-5.73e-01	0.0667
3371	TNC	LZE22D1	Human	Esophagus	HGIN	5.44e-03	-5.51e-01	0.0595
3371	TNC	LZE24T	Human	Esophagus	ESCC	1.00e-04	-5.08e-01	0.0596
3371	TNC	P9T-E	Human	Esophagus	ESCC	1.63e-15	1.15e+00	0.1131
3371	TNC	P10T-E	Human	Esophagus	ESCC	8.75e-49	1.80e+00	0.116
3371	TNC	P11T-E	Human	Esophagus	ESCC	5.31e-21	2.62e+00	0.1426
3371	TNC	P12T-E	Human	Esophagus	ESCC	2.64e-45	2.21e+00	0.1122
3371	TNC	P15T-E	Human	Esophagus	ESCC	2.19e-34	2.29e+00	0.1149
3371	TNC	P16T-E	Human	Esophagus	ESCC	1.89e-13	-5.68e-01	0.1153
3371	TNC	P17T-E	Human	Esophagus	ESCC	1.42e-12	1.56e+00	0.1278
3371	TNC	P19T-E	Human	Esophagus	ESCC	1.60e-02	1.31e+00	0.1662
3371	TNC	P21T-E	Human	Esophagus	ESCC	1.06e-61	3.52e+00	0.1617
3371	TNC	P22T-E	Human	Esophagus	ESCC	2.21e-05	3.17e-01	0.1236
3371	TNC	P24T-E	Human	Esophagus	ESCC	2.80e-05	9.41e-01	0.1287
3371	TNC	P26T-E	Human	Esophagus	ESCC	6.75e-36	1.87e+00	0.1276
3371	TNC	P27T-E	Human	Esophagus	ESCC	2.27e-02	9.22e-01	0.1055
3371	TNC	P28T-E	Human	Esophagus	ESCC	4.61e-03	4.61e-03	0.1149
3371	TNC	P30T-E	Human	Esophagus	ESCC	6.96e-04	2.02e+00	0.137

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:004206028	Skin	AK	wound healing	91/1910	422/18723	2.93e-12	6.67e-10	91
GO:004873226	Skin	AK	gland development	93/1910	436/18723	3.24e-12	7.10e-10	93
GO:006156416	Skin	AK	axon development	91/1910	467/18723	8.60e-10	8.63e-08	91
GO:000164919	Skin	AK	osteoblast differentiation	52/1910	229/18723	2.27e-08	1.28e-06	52
GO:000150318	Skin	AK	ossification	78/1910	408/18723	3.26e-08	1.76e-06	78
GO:002261217	Skin	AK	gland morphogenesis	32/1910	118/18723	1.68e-07	7.09e-06	32
GO:007149627	Skin	AK	cellular response to external stimulus	63/1910	320/18723	2.30e-07	9.13e-06	63
GO:004860819	Skin	AK	reproductive structure development	77/1910	424/18723	3.56e-07	1.36e-05	77
GO:006145820	Skin	AK	reproductive system development	77/1910	427/18723	4.76e-07	1.74e-05	77
GO:190165425	Skin	AK	response to ketone	43/1910	194/18723	7.32e-07	2.49e-05	43
GO:006056016	Skin	AK	developmental growth involved in morphogenesis	47/1910	234/18723	4.30e-06	1.05e-04	47
GO:000716210	Skin	AK	negative regulation of cell adhesion	55/1910	303/18723	1.64e-05	3.15e-04	55
GO:003109917	Skin	AK	regeneration	40/1910	198/18723	1.88e-05	3.52e-04	40
GO:00508088	Skin	AK	synapse organization	71/1910	426/18723	2.21e-05	4.07e-04	71
GO:00717743	Skin	AK	response to fibroblast growth factor	28/1910	120/18723	2.23e-05	4.08e-04	28
GO:000961217	Skin	AK	response to mechanical stimulus	42/1910	216/18723	3.07e-05	5.21e-04	42
GO:003166824	Skin	AK	cellular response to extracellular stimulus	46/1910	246/18723	3.67e-05	6.11e-04	46
GO:00308507	Skin	AK	prostate gland development	14/1910	45/18723	9.94e-05	1.32e-03	14
GO:006056216	Skin	AK	epithelial tube morphogenesis	55/1910	325/18723	1.19e-04	1.50e-03	55
GO:000176310	Skin	AK	morphogenesis of a branching structure	37/1910	196/18723	1.67e-04	1.94e-03	37

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0516510	Esophagus	ESCC	Human papillomavirus infection	215/4205	331/8465	7.86e-09	7.12e-08	3.65e-08	215
hsa0451020	Esophagus	ESCC	Focal adhesion	127/4205	203/8465	1.25e-04	4.99e-04	2.56e-04	127
hsa041517	Esophagus	ESCC	PI3K-Akt signaling pathway	197/4205	354/8465	1.24e-02	2.83e-02	1.45e-02	197
hsa0516515	Esophagus	ESCC	Human papillomavirus infection	215/4205	331/8465	7.86e-09	7.12e-08	3.65e-08	215
hsa04510111	Esophagus	ESCC	Focal adhesion	127/4205	203/8465	1.25e-04	4.99e-04	2.56e-04	127
hsa0415114	Esophagus	ESCC	PI3K-Akt signaling pathway	197/4205	354/8465	1.24e-02	2.83e-02	1.45e-02	197
hsa0451021	Liver	Cirrhotic	Focal adhesion	93/2530	203/8465	9.27e-07	1.10e-05	6.80e-06	93
hsa05165	Liver	Cirrhotic	Human papillomavirus infection	124/2530	331/8465	1.55e-03	7.83e-03	4.83e-03	124
hsa0451031	Liver	Cirrhotic	Focal adhesion	93/2530	203/8465	9.27e-07	1.10e-05	6.80e-06	93
hsa051651	Liver	Cirrhotic	Human papillomavirus infection	124/2530	331/8465	1.55e-03	7.83e-03	4.83e-03	124
hsa051652	Liver	HCC	Human papillomavirus infection	188/4020	331/8465	3.34e-04	1.49e-03	8.29e-04	188
hsa051653	Liver	HCC	Human papillomavirus infection	188/4020	331/8465	3.34e-04	1.49e-03	8.29e-04	188
hsa045108	Lung	IAC	Focal adhesion	59/1053	203/8465	1.31e-10	1.06e-08	7.06e-09	59
hsa051656	Lung	IAC	Human papillomavirus infection	71/1053	331/8465	1.88e-06	7.63e-05	5.06e-05	71
hsa04512	Lung	IAC	ECM-receptor interaction	20/1053	89/8465	5.65e-03	2.45e-02	1.63e-02	20
hsa041514	Lung	IAC	PI3K-Akt signaling pathway	60/1053	354/8465	7.03e-03	2.86e-02	1.90e-02	60
hsa0451012	Lung	IAC	Focal adhesion	59/1053	203/8465	1.31e-10	1.06e-08	7.06e-09	59
hsa0516511	Lung	IAC	Human papillomavirus infection	71/1053	331/8465	1.88e-06	7.63e-05	5.06e-05	71
hsa045121	Lung	IAC	ECM-receptor interaction	20/1053	89/8465	5.65e-03	2.45e-02	1.63e-02	20
hsa0415111	Lung	IAC	PI3K-Akt signaling pathway	60/1053	354/8465	7.03e-03	2.86e-02	1.90e-02	60

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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
TNC	SDC4	TNC_SDC4	TENASCIN	Breast	ADJ
TNC	SDC1	TNC_SDC1	TENASCIN	Breast	DCIS
TNC	SDC4	TNC_SDC4	TENASCIN	Breast	DCIS
TNC	ITGAV_ITGB6	TNC_ITGAV_ITGB6	TENASCIN	Breast	Healthy
TNC	SDC1	TNC_SDC1	TENASCIN	Breast	Healthy
TNC	SDC4	TNC_SDC4	TENASCIN	Breast	Healthy
TNC	SDC4	TNC_SDC4	TENASCIN	Breast	Precancer
TNC	ITGA8_ITGB1	TNC_ITGA8_ITGB1	TENASCIN	Cervix	ADJ
TNC	SDC1	TNC_SDC1	TENASCIN	Cervix	ADJ
TNC	SDC4	TNC_SDC4	TENASCIN	Cervix	ADJ
TNC	ITGA8_ITGB1	TNC_ITGA8_ITGB1	TENASCIN	Cervix	CC
TNC	ITGA9_ITGB1	TNC_ITGA9_ITGB1	TENASCIN	Cervix	CC
TNC	ITGAV_ITGB6	TNC_ITGAV_ITGB6	TENASCIN	Cervix	CC
TNC	SDC1	TNC_SDC1	TENASCIN	Cervix	CC
TNC	SDC4	TNC_SDC4	TENASCIN	Cervix	CC
TNC	ITGA8_ITGB1	TNC_ITGA8_ITGB1	TENASCIN	Cervix	Healthy
TNC	SDC1	TNC_SDC1	TENASCIN	Cervix	Healthy
TNC	SDC4	TNC_SDC4	TENASCIN	Cervix	Healthy
TNC	ITGA8_ITGB1	TNC_ITGA8_ITGB1	TENASCIN	Cervix	Precancer
TNC	SDC1	TNC_SDC1	TENASCIN	Cervix	Precancer

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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

TNC

SNV

Missense_Mutation

c.2848N>G

p.Thr950Ala

p.T950A

P24821

protein_coding

tolerated(0.95)

benign(0.009)

TCGA-A2-A04Y-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

TNC

SNV

Missense_Mutation

rs200602864

c.5528N>A

p.Arg1843His

p.R1843H

P24821

protein_coding

tolerated(0.12)

benign(0.103)

TCGA-A7-A0CE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

TNC

SNV

Missense_Mutation

rs200465690

c.6026C>T

p.Ala2009Val

p.A2009V

P24821

protein_coding

deleterious(0.01)

benign(0.364)

TCGA-A7-A0CG-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TNC

SNV

Missense_Mutation

c.2905N>C

p.Lys969Gln

p.K969Q

P24821

protein_coding

deleterious(0.05)

benign(0.299)

TCGA-A8-A081-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TNC

SNV

Missense_Mutation

novel

c.2027N>G

p.Ser676Cys

p.S676C

P24821

protein_coding

deleterious(0)

probably_damaging(0.984)

TCGA-A8-A09B-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

5-fluorouracil

TNC

SNV

Missense_Mutation

rs748790119

c.1496N>A

p.Arg499His

p.R499H

P24821

protein_coding

deleterious(0.05)

benign(0)

TCGA-AC-A23E-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

TNC

SNV

Missense_Mutation

rs146024320

c.5174N>T

p.Ser1725Leu

p.S1725L

P24821

protein_coding

deleterious(0.01)

possibly_damaging(0.869)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TNC

SNV

Missense_Mutation

novel

c.2213N>T

p.Ala738Val

p.A738V

P24821

protein_coding

deleterious(0.02)

possibly_damaging(0.777)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TNC

SNV

Missense_Mutation

rs781414339

c.3764A>G

p.Glu1255Gly

p.E1255G

P24821

protein_coding

tolerated(0.19)

benign(0.007)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TNC

SNV

Missense_Mutation

novel

c.4108N>T

p.Ala1370Ser

p.A1370S

P24821

protein_coding

tolerated(0.51)

benign(0.345)

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

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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
3371	TNC	DRUGGABLE GENOME, FIBRINOGEN		CHEMBL2109584	F16SIP 131I
3371	TNC	DRUGGABLE GENOME, FIBRINOGEN		F-16-131I
3371	TNC	DRUGGABLE GENOME, FIBRINOGEN		NEURADIAB
3371	TNC	DRUGGABLE GENOME, FIBRINOGEN		CHEMBL2109582	81C6 131I
3371	TNC	DRUGGABLE GENOME, FIBRINOGEN		8H9	8H9 131I
3371	TNC	DRUGGABLE GENOME, FIBRINOGEN		CHEMBL1743077	TENATUMOMAB
3371	TNC	DRUGGABLE GENOME, FIBRINOGEN		F-16-IL-2 fusion protein
3371	TNC	DRUGGABLE GENOME, FIBRINOGEN		CHEMBL2109583	F16IL2

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