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: TJP2

Gene summary for TJP2

Gene summary.

Gene information	Species	Human
	Gene symbol	TJP2
	Gene ID	9414
	Gene name	tight junction protein 2
	Gene Alias	C9DUPq21.11
	Cytomap	9q21.11
	Gene Type	protein-coding
	GO ID	GO:0001885
	UniProtAcc	B7Z2R3

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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
9414	TJP2	HTA11_3410_2000001011	Human	Colorectum	AD	3.91e-24	4.48e-01	0.0155
9414	TJP2	HTA11_2487_2000001011	Human	Colorectum	SER	2.53e-34	8.74e-01	-0.1808
9414	TJP2	HTA11_2951_2000001011	Human	Colorectum	AD	3.03e-06	3.04e-01	0.0216
9414	TJP2	HTA11_1938_2000001011	Human	Colorectum	AD	3.12e-39	9.41e-01	-0.0811
9414	TJP2	HTA11_78_2000001011	Human	Colorectum	AD	1.25e-39	8.67e-01	-0.1088
9414	TJP2	HTA11_347_2000001011	Human	Colorectum	AD	1.74e-63	1.06e+00	-0.1954
9414	TJP2	HTA11_411_2000001011	Human	Colorectum	SER	3.33e-15	1.09e+00	-0.2602
9414	TJP2	HTA11_2112_2000001011	Human	Colorectum	SER	1.23e-14	7.92e-01	-0.2196
9414	TJP2	HTA11_3361_2000001011	Human	Colorectum	AD	3.79e-24	6.18e-01	-0.1207
9414	TJP2	HTA11_83_2000001011	Human	Colorectum	SER	1.40e-25	7.48e-01	-0.1526
9414	TJP2	HTA11_696_2000001011	Human	Colorectum	AD	3.76e-36	6.65e-01	-0.1464
9414	TJP2	HTA11_866_2000001011	Human	Colorectum	AD	1.49e-43	7.19e-01	-0.1001
9414	TJP2	HTA11_1391_2000001011	Human	Colorectum	AD	4.62e-41	9.59e-01	-0.059
9414	TJP2	HTA11_2992_2000001011	Human	Colorectum	SER	2.24e-14	5.61e-01	-0.1706
9414	TJP2	HTA11_5212_2000001011	Human	Colorectum	AD	2.34e-19	6.80e-01	-0.2061
9414	TJP2	HTA11_5216_2000001011	Human	Colorectum	SER	2.79e-07	5.34e-01	-0.1462
9414	TJP2	HTA11_546_2000001011	Human	Colorectum	AD	1.59e-23	6.21e-01	-0.0842
9414	TJP2	HTA11_9341_2000001011	Human	Colorectum	SER	2.78e-05	3.27e-01	-0.00410000000000005
9414	TJP2	HTA11_7862_2000001011	Human	Colorectum	AD	1.85e-13	5.37e-01	-0.0179
9414	TJP2	HTA11_866_3004761011	Human	Colorectum	AD	1.05e-24	5.09e-01	0.096

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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
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
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

∗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:0009150	Colorectum	AD	purine ribonucleotide metabolic process	142/3918	368/18723	4.29e-15	1.17e-12	142
GO:0006163	Colorectum	AD	purine nucleotide metabolic process	149/3918	396/18723	1.08e-14	2.80e-12	149
GO:0072521	Colorectum	AD	purine-containing compound metabolic process	153/3918	416/18723	4.34e-14	1.01e-11	153
GO:0009259	Colorectum	AD	ribonucleotide metabolic process	144/3918	385/18723	5.25e-14	1.13e-11	144
GO:0019693	Colorectum	AD	ribose phosphate metabolic process	145/3918	396/18723	3.01e-13	5.71e-11	145
GO:0009117	Colorectum	AD	nucleotide metabolic process	168/3918	489/18723	2.20e-12	3.36e-10	168
GO:0006753	Colorectum	AD	nucleoside phosphate metabolic process	169/3918	497/18723	4.99e-12	6.98e-10	169
GO:0002064	Colorectum	AD	epithelial cell development	89/3918	220/18723	2.98e-11	3.52e-09	89
GO:0045216	Colorectum	AD	cell-cell junction organization	80/3918	200/18723	5.57e-10	4.58e-08	80
GO:0009135	Colorectum	AD	purine nucleoside diphosphate metabolic process	47/3918	103/18723	1.61e-08	9.22e-07	47
GO:0009179	Colorectum	AD	purine ribonucleoside diphosphate metabolic process	47/3918	103/18723	1.61e-08	9.22e-07	47
GO:0009185	Colorectum	AD	ribonucleoside diphosphate metabolic process	47/3918	106/18723	4.85e-08	2.55e-06	47
GO:0034109	Colorectum	AD	homotypic cell-cell adhesion	40/3918	90/18723	4.37e-07	1.67e-05	40
GO:0009132	Colorectum	AD	nucleoside diphosphate metabolic process	49/3918	124/18723	1.75e-06	5.31e-05	49
GO:0061028	Colorectum	AD	establishment of endothelial barrier	23/3918	46/18723	1.14e-05	2.57e-04	23
GO:0060249	Colorectum	AD	anatomical structure homeostasis	94/3918	314/18723	9.37e-05	1.42e-03	94
GO:0090559	Colorectum	AD	regulation of membrane permeability	31/3918	78/18723	1.16e-04	1.72e-03	31
GO:0001894	Colorectum	AD	tissue homeostasis	81/3918	268/18723	1.96e-04	2.62e-03	81
GO:0001885	Colorectum	AD	endothelial cell development	26/3918	64/18723	2.67e-04	3.29e-03	26
GO:0009126	Colorectum	AD	purine nucleoside monophosphate metabolic process	19/3918	44/18723	7.13e-04	7.21e-03	19

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04530	Colorectum	AD	Tight junction	76/2092	169/8465	5.49e-09	9.69e-08	6.18e-08	76
hsa05110	Colorectum	AD	Vibrio cholerae infection	29/2092	50/8465	5.10e-07	7.12e-06	4.54e-06	29
hsa045301	Colorectum	AD	Tight junction	76/2092	169/8465	5.49e-09	9.69e-08	6.18e-08	76
hsa051101	Colorectum	AD	Vibrio cholerae infection	29/2092	50/8465	5.10e-07	7.12e-06	4.54e-06	29
hsa045302	Colorectum	SER	Tight junction	59/1580	169/8465	3.24e-07	5.98e-06	4.34e-06	59
hsa051102	Colorectum	SER	Vibrio cholerae infection	24/1580	50/8465	2.17e-06	3.13e-05	2.28e-05	24
hsa045303	Colorectum	SER	Tight junction	59/1580	169/8465	3.24e-07	5.98e-06	4.34e-06	59
hsa051103	Colorectum	SER	Vibrio cholerae infection	24/1580	50/8465	2.17e-06	3.13e-05	2.28e-05	24
hsa045304	Colorectum	MSS	Tight junction	66/1875	169/8465	4.10e-07	6.25e-06	3.83e-06	66
hsa051104	Colorectum	MSS	Vibrio cholerae infection	27/1875	50/8465	8.58e-07	1.20e-05	7.34e-06	27
hsa045305	Colorectum	MSS	Tight junction	66/1875	169/8465	4.10e-07	6.25e-06	3.83e-06	66
hsa051105	Colorectum	MSS	Vibrio cholerae infection	27/1875	50/8465	8.58e-07	1.20e-05	7.34e-06	27
hsa045306	Colorectum	MSI-H	Tight junction	31/797	169/8465	2.08e-04	2.80e-03	2.35e-03	31
hsa045307	Colorectum	MSI-H	Tight junction	31/797	169/8465	2.08e-04	2.80e-03	2.35e-03	31
hsa04530211	Esophagus	ESCC	Tight junction	105/4205	169/8465	6.73e-04	2.23e-03	1.14e-03	105
hsa0511028	Esophagus	ESCC	Vibrio cholerae infection	34/4205	50/8465	6.62e-03	1.62e-02	8.30e-03	34
hsa04530310	Esophagus	ESCC	Tight junction	105/4205	169/8465	6.73e-04	2.23e-03	1.14e-03	105
hsa05110112	Esophagus	ESCC	Vibrio cholerae infection	34/4205	50/8465	6.62e-03	1.62e-02	8.30e-03	34
hsa0453030	Oral cavity	OSCC	Tight junction	102/3704	169/8465	8.68e-06	3.93e-05	2.00e-05	102
hsa0511026	Oral cavity	OSCC	Vibrio cholerae infection	32/3704	50/8465	3.05e-03	7.74e-03	3.94e-03	32

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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

TJP2

SNV

Missense_Mutation

novel

c.2350N>T

p.Asp784Tyr

p.D784Y

Q9UDY2

protein_coding

deleterious(0)

benign(0.428)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

TJP2

SNV

Missense_Mutation

rs748504603

c.2930T>G

p.Val977Gly

p.V977G

Q9UDY2

protein_coding

tolerated(0.08)

benign(0.012)

TCGA-A2-A04Q-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

TJP2

SNV

Missense_Mutation

rs748504603

c.2930T>G

p.Val977Gly

p.V977G

Q9UDY2

protein_coding

tolerated(0.08)

benign(0.012)

TCGA-A2-A1G0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

TJP2

SNV

Missense_Mutation

rs73450853

c.43N>C

p.Val15Leu

p.V15L

Q9UDY2

protein_coding

tolerated_low_confidence(0.58)

benign(0.009)

TCGA-AC-A3EH-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

TJP2

SNV

Missense_Mutation

rs748504603

c.2930N>G

p.Val977Gly

p.V977G

Q9UDY2

protein_coding

tolerated(0.08)

benign(0.012)

TCGA-B6-A1KN-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

TJP2

SNV

Missense_Mutation

rs748504603

c.2930N>G

p.Val977Gly

p.V977G

Q9UDY2

protein_coding

tolerated(0.08)

benign(0.012)

TCGA-BH-A0HU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

TJP2

SNV

Missense_Mutation

rs748504603

c.2930N>G

p.Val977Gly

p.V977G

Q9UDY2

protein_coding

tolerated(0.08)

benign(0.012)

TCGA-BH-A1F5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TJP2

SNV

Missense_Mutation

rs748504603

c.2930N>G

p.Val977Gly

p.V977G

Q9UDY2

protein_coding

tolerated(0.08)

benign(0.012)

TCGA-BH-A1FH-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

TJP2

SNV

Missense_Mutation

rs748504603

c.2930T>G

p.Val977Gly

p.V977G

Q9UDY2

protein_coding

tolerated(0.08)

benign(0.012)

TCGA-C8-A1HO-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

5-fluorouracil

TJP2

SNV

Missense_Mutation

c.2617N>G

p.Gln873Glu

p.Q873E

Q9UDY2

protein_coding

deleterious(0)

probably_damaging(0.979)

TCGA-C8-A275-01

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

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