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: TJP1

Gene summary for TJP1

Gene summary.

Gene information	Species	Human
	Gene symbol	TJP1
	Gene ID	7082
	Gene name	tight junction protein 1
	Gene Alias	ZO-1
	Cytomap	15q13.1
	Gene Type	protein-coding
	GO ID	GO:0001525
	UniProtAcc	A9CQZ8

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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
7082	TJP1	CA_HPV_1	Human	Cervix	CC	1.81e-04	-1.72e-01	0.0264
7082	TJP1	N_HPV_1	Human	Cervix	N_HPV	5.00e-02	-1.75e-01	0.0079
7082	TJP1	CCI_2	Human	Cervix	CC	2.61e-04	9.92e-01	0.5249
7082	TJP1	CCI_3	Human	Cervix	CC	1.60e-07	6.76e-01	0.516
7082	TJP1	T2	Human	Cervix	CC	5.50e-05	4.90e-01	0.0709
7082	TJP1	HTA11_3410_2000001011	Human	Colorectum	AD	3.24e-06	-4.15e-01	0.0155
7082	TJP1	HTA11_99999965062_69753	Human	Colorectum	MSI-H	7.03e-04	9.18e-01	0.3487
7082	TJP1	A002-C-010	Human	Colorectum	FAP	2.23e-04	-2.15e-01	0.242
7082	TJP1	A015-C-203	Human	Colorectum	FAP	1.85e-23	-4.32e-01	-0.1294
7082	TJP1	A015-C-204	Human	Colorectum	FAP	2.17e-05	-2.77e-01	-0.0228
7082	TJP1	A014-C-040	Human	Colorectum	FAP	2.37e-02	-3.41e-01	-0.1184
7082	TJP1	A002-C-201	Human	Colorectum	FAP	6.84e-10	-3.25e-01	0.0324
7082	TJP1	A002-C-203	Human	Colorectum	FAP	7.71e-04	-2.27e-01	0.2786
7082	TJP1	A001-C-119	Human	Colorectum	FAP	6.98e-06	-1.42e-01	-0.1557
7082	TJP1	A001-C-108	Human	Colorectum	FAP	4.92e-11	-1.44e-01	-0.0272
7082	TJP1	A002-C-205	Human	Colorectum	FAP	1.92e-14	-2.80e-01	-0.1236
7082	TJP1	A015-C-005	Human	Colorectum	FAP	8.77e-05	-2.89e-01	-0.0336
7082	TJP1	A015-C-006	Human	Colorectum	FAP	5.17e-11	-3.41e-01	-0.0994
7082	TJP1	A015-C-106	Human	Colorectum	FAP	1.56e-12	-2.85e-01	-0.0511
7082	TJP1	A002-C-114	Human	Colorectum	FAP	1.38e-13	-3.81e-01	-0.1561

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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
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
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:003295621	Stomach	CSG	regulation of actin cytoskeleton organization	47/1034	358/18723	3.10e-08	2.49e-06	47
GO:006157221	Stomach	CSG	actin filament bundle organization	28/1034	161/18723	5.97e-08	4.39e-06	28
GO:005101721	Stomach	CSG	actin filament bundle assembly	27/1034	157/18723	1.30e-07	9.05e-06	27
GO:003153221	Stomach	CSG	actin cytoskeleton reorganization	20/1034	107/18723	1.42e-06	6.87e-05	20
GO:004521621	Stomach	CSG	cell-cell junction organization	29/1034	200/18723	1.82e-06	8.48e-05	29
GO:00224072	Stomach	CSG	regulation of cell-cell adhesion	48/1034	448/18723	8.67e-06	3.05e-04	48
GO:004578521	Stomach	CSG	positive regulation of cell adhesion	47/1034	437/18723	9.72e-06	3.36e-04	47
GO:003223121	Stomach	CSG	regulation of actin filament bundle assembly	18/1034	105/18723	1.65e-05	5.12e-04	18
GO:011002021	Stomach	CSG	regulation of actomyosin structure organization	17/1034	100/18723	3.14e-05	8.74e-04	17
GO:000206421	Stomach	CSG	epithelial cell development	28/1034	220/18723	3.30e-05	9.05e-04	28
GO:005149221	Stomach	CSG	regulation of stress fiber assembly	16/1034	91/18723	3.47e-05	9.37e-04	16
GO:003003821	Stomach	CSG	contractile actin filament bundle assembly	17/1034	106/18723	6.74e-05	1.65e-03	17
GO:004314921	Stomach	CSG	stress fiber assembly	17/1034	106/18723	6.74e-05	1.65e-03	17
GO:001063921	Stomach	CSG	negative regulation of organelle organization	36/1034	348/18723	2.25e-04	4.25e-03	36
GO:00224092	Stomach	CSG	positive regulation of cell-cell adhesion	31/1034	284/18723	2.35e-04	4.37e-03	31
GO:004329721	Stomach	CSG	apical junction assembly	13/1034	78/18723	3.20e-04	5.43e-03	13
GO:012019321	Stomach	CSG	tight junction organization	13/1034	80/18723	4.13e-04	6.56e-03	13
GO:003103221	Stomach	CSG	actomyosin structure organization	23/1034	196/18723	5.29e-04	7.97e-03	23
GO:006102821	Stomach	CSG	establishment of endothelial barrier	9/1034	46/18723	7.99e-04	1.09e-02	9
GO:190290421	Stomach	CSG	negative regulation of supramolecular fiber organization	20/1034	167/18723	9.20e-04	1.22e-02	20

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0513020	Cervix	CC	Pathogenic Escherichia coli infection	63/1267	197/8465	9.28e-10	2.00e-08	1.19e-08	63
hsa0452020	Cervix	CC	Adherens junction	33/1267	93/8465	6.99e-07	7.31e-06	4.32e-06	33
hsa0453020	Cervix	CC	Tight junction	49/1267	169/8465	1.87e-06	1.78e-05	1.05e-05	49
hsa051207	Cervix	CC	Epithelial cell signaling in Helicobacter pylori infection	24/1267	70/8465	4.35e-05	3.09e-04	1.83e-04	24
hsa0511016	Cervix	CC	Vibrio cholerae infection	18/1267	50/8465	1.91e-04	1.11e-03	6.55e-04	18
hsa04540	Cervix	CC	Gap junction	22/1267	88/8465	9.07e-03	2.85e-02	1.69e-02	22
hsa05130110	Cervix	CC	Pathogenic Escherichia coli infection	63/1267	197/8465	9.28e-10	2.00e-08	1.19e-08	63
hsa04520110	Cervix	CC	Adherens junction	33/1267	93/8465	6.99e-07	7.31e-06	4.32e-06	33
hsa04530110	Cervix	CC	Tight junction	49/1267	169/8465	1.87e-06	1.78e-05	1.05e-05	49
hsa0512014	Cervix	CC	Epithelial cell signaling in Helicobacter pylori infection	24/1267	70/8465	4.35e-05	3.09e-04	1.83e-04	24
hsa0511017	Cervix	CC	Vibrio cholerae infection	18/1267	50/8465	1.91e-04	1.11e-03	6.55e-04	18
hsa045401	Cervix	CC	Gap junction	22/1267	88/8465	9.07e-03	2.85e-02	1.69e-02	22
hsa0513044	Cervix	N_HPV	Pathogenic Escherichia coli infection	25/349	197/8465	4.71e-07	8.00e-06	6.25e-06	25
hsa0511023	Cervix	N_HPV	Vibrio cholerae infection	8/349	50/8465	9.07e-04	6.49e-03	5.08e-03	8
hsa0453025	Cervix	N_HPV	Tight junction	16/349	169/8465	1.60e-03	1.01e-02	7.92e-03	16
hsa0513054	Cervix	N_HPV	Pathogenic Escherichia coli infection	25/349	197/8465	4.71e-07	8.00e-06	6.25e-06	25
hsa0511033	Cervix	N_HPV	Vibrio cholerae infection	8/349	50/8465	9.07e-04	6.49e-03	5.08e-03	8
hsa0453035	Cervix	N_HPV	Tight junction	16/349	169/8465	1.60e-03	1.01e-02	7.92e-03	16
hsa04520	Colorectum	AD	Adherens junction	50/2092	93/8465	1.52e-09	2.83e-08	1.81e-08	50
hsa04530	Colorectum	AD	Tight junction	76/2092	169/8465	5.49e-09	9.69e-08	6.18e-08	76

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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

TJP1

SNV

Missense_Mutation

c.5013N>G

p.Ile1671Met

p.I1671M

protein_coding

deleterious(0)

probably_damaging(0.924)

TCGA-A8-A09A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

TJP1

SNV

Missense_Mutation

c.3556G>A

p.Ala1186Thr

p.A1186T

protein_coding

tolerated_low_confidence(0.1)

benign(0.001)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TJP1

SNV

Missense_Mutation

novel

c.3859G>T

p.Asp1287Tyr

p.D1287Y

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.503)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TJP1

SNV

Missense_Mutation

rs761548583

c.3202N>A

p.Asp1068Asn

p.D1068N

protein_coding

deleterious_low_confidence(0)

benign(0.248)

TCGA-AR-A0TQ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

TJP1

SNV

Missense_Mutation

c.155N>A

p.Thr52Lys

p.T52K

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AR-A0TS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

TJP1

SNV

Missense_Mutation

novel

c.3617N>A

p.Gly1206Glu

p.G1206E

protein_coding

deleterious_low_confidence(0.01)

benign(0.234)

TCGA-AR-A0TU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Doxorubicin

TJP1

SNV

Missense_Mutation

c.855G>C

p.Glu285Asp

p.E285D

protein_coding

tolerated(0.73)

benign(0.014)

TCGA-C8-A1HM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

TJP1

SNV

Missense_Mutation

novel

c.1741N>C

p.Glu581Gln

p.E581Q

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-C8-A8HP-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

5-fluorouracil

TJP1

SNV

Missense_Mutation

c.2078N>T

p.Thr693Ile

p.T693I

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-D8-A1J8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

nolvadex

TJP1

SNV

Missense_Mutation

c.4102N>C

p.Glu1368Gln

p.E1368Q

protein_coding

tolerated_low_confidence(0.08)

possibly_damaging(0.628)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

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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
7082	TJP1	KINASE, TRANSCRIPTION FACTOR		risperidone	RISPERIDONE
7082	TJP1	KINASE, TRANSCRIPTION FACTOR		DEXAMETHASONE	DEXAMETHASONE	8206910
7082	TJP1	KINASE, TRANSCRIPTION FACTOR		GENISTEIN	GENISTEIN	10330056
7082	TJP1	KINASE, TRANSCRIPTION FACTOR		ETHANOL	ALCOHOL	9952110

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