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: VCAM1

Gene summary for VCAM1

Gene summary.

Gene information	Species	Human
	Gene symbol	VCAM1
	Gene ID	7412
	Gene name	vascular cell adhesion molecule 1
	Gene Alias	CD106
	Cytomap	1p21.2
	Gene Type	protein-coding
	GO ID	GO:0001666
	UniProtAcc	P19320

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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
7412	VCAM1	P2T-E	Human	Esophagus	ESCC	5.21e-54	1.32e+00	0.1177
7412	VCAM1	P4T-E	Human	Esophagus	ESCC	2.78e-03	3.35e-01	0.1323
7412	VCAM1	P5T-E	Human	Esophagus	ESCC	3.75e-03	1.64e-01	0.1327
7412	VCAM1	P9T-E	Human	Esophagus	ESCC	4.07e-07	3.97e-01	0.1131
7412	VCAM1	P16T-E	Human	Esophagus	ESCC	1.66e-02	8.35e-02	0.1153
7412	VCAM1	P24T-E	Human	Esophagus	ESCC	4.41e-07	2.46e-01	0.1287
7412	VCAM1	P36T-E	Human	Esophagus	ESCC	4.60e-04	6.13e-01	0.1187
7412	VCAM1	P44T-E	Human	Esophagus	ESCC	2.39e-04	3.23e-01	0.1096
7412	VCAM1	P47T-E	Human	Esophagus	ESCC	1.66e-02	2.18e-01	0.1067
7412	VCAM1	C38	Human	Oral cavity	OSCC	1.77e-07	1.00e+00	0.172
7412	VCAM1	C43	Human	Oral cavity	OSCC	8.10e-82	2.03e+00	0.1704
7412	VCAM1	C46	Human	Oral cavity	OSCC	1.05e-15	7.12e-01	0.1673
7412	VCAM1	LN46	Human	Oral cavity	OSCC	3.28e-09	6.71e-01	0.1666
7412	VCAM1	EOLP-2	Human	Oral cavity	EOLP	1.45e-03	2.53e-01	-0.0203
7412	VCAM1	NEOLP-1	Human	Oral cavity	NEOLP	3.78e-06	2.38e-01	-0.0194
7412	VCAM1	NEOLP-2	Human	Oral cavity	NEOLP	3.45e-03	2.08e-01	-0.0196
7412	VCAM1	NEOLP-3	Human	Oral cavity	NEOLP	1.29e-13	3.93e-01	-0.0191

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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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma

∗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:000716023	Oral cavity	NEOLP	cell-matrix adhesion	62/2005	233/18723	6.73e-12	1.14e-09	62
GO:190165331	Oral cavity	NEOLP	cellular response to peptide	78/2005	359/18723	7.21e-10	5.54e-08	78
GO:004578532	Oral cavity	NEOLP	positive regulation of cell adhesion	88/2005	437/18723	3.28e-09	1.95e-07	88
GO:000756831	Oral cavity	NEOLP	aging	69/2005	339/18723	1.05e-07	3.83e-06	69
GO:003461231	Oral cavity	NEOLP	response to tumor necrosis factor	55/2005	253/18723	2.23e-07	7.28e-06	55
GO:007048232	Oral cavity	NEOLP	response to oxygen levels	69/2005	347/18723	2.66e-07	8.54e-06	69
GO:000166632	Oral cavity	NEOLP	response to hypoxia	63/2005	307/18723	2.75e-07	8.78e-06	63
GO:003629332	Oral cavity	NEOLP	response to decreased oxygen levels	65/2005	322/18723	3.34e-07	1.04e-05	65
GO:007135631	Oral cavity	NEOLP	cellular response to tumor necrosis factor	50/2005	229/18723	6.79e-07	1.93e-05	50
GO:002240724	Oral cavity	NEOLP	regulation of cell-cell adhesion	81/2005	448/18723	1.54e-06	3.83e-05	81
GO:000715923	Oral cavity	NEOLP	leukocyte cell-cell adhesion	70/2005	371/18723	1.65e-06	4.05e-05	70
GO:004211031	Oral cavity	NEOLP	T cell activation	86/2005	487/18723	2.01e-06	4.77e-05	86
GO:190313122	Oral cavity	NEOLP	mononuclear cell differentiation	77/2005	426/18723	2.80e-06	6.41e-05	77
GO:003249631	Oral cavity	NEOLP	response to lipopolysaccharide	65/2005	343/18723	3.30e-06	7.40e-05	65
GO:000223731	Oral cavity	NEOLP	response to molecule of bacterial origin	67/2005	363/18723	5.94e-06	1.20e-04	67
GO:005090023	Oral cavity	NEOLP	leukocyte migration	67/2005	369/18723	1.04e-05	1.96e-04	67
GO:190303723	Oral cavity	NEOLP	regulation of leukocyte cell-cell adhesion	61/2005	336/18723	2.56e-05	4.01e-04	61
GO:003166831	Oral cavity	NEOLP	cellular response to extracellular stimulus	48/2005	246/18723	2.80e-05	4.32e-04	48
GO:001003833	Oral cavity	NEOLP	response to metal ion	66/2005	373/18723	2.83e-05	4.34e-04	66
GO:003009821	Oral cavity	NEOLP	lymphocyte differentiation	66/2005	374/18723	3.08e-05	4.67e-04	66

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05418211	Esophagus	ESCC	Fluid shear stress and atherosclerosis	109/4205	139/8465	2.00e-12	3.72e-11	1.90e-11	109
hsa0466810	Esophagus	ESCC	TNF signaling pathway	89/4205	114/8465	3.36e-10	4.01e-09	2.06e-09	89
hsa05417211	Esophagus	ESCC	Lipid and atherosclerosis	143/4205	215/8465	3.30e-07	2.45e-06	1.26e-06	143
hsa0493310	Esophagus	ESCC	AGE-RAGE signaling pathway in diabetic complications	72/4205	100/8465	4.15e-06	2.28e-05	1.17e-05	72
hsa05418310	Esophagus	ESCC	Fluid shear stress and atherosclerosis	109/4205	139/8465	2.00e-12	3.72e-11	1.90e-11	109
hsa0466817	Esophagus	ESCC	TNF signaling pathway	89/4205	114/8465	3.36e-10	4.01e-09	2.06e-09	89
hsa05417310	Esophagus	ESCC	Lipid and atherosclerosis	143/4205	215/8465	3.30e-07	2.45e-06	1.26e-06	143
hsa0493317	Esophagus	ESCC	AGE-RAGE signaling pathway in diabetic complications	72/4205	100/8465	4.15e-06	2.28e-05	1.17e-05	72
hsa046689	Oral cavity	OSCC	TNF signaling pathway	82/3704	114/8465	8.30e-10	9.59e-09	4.88e-09	82
hsa0541830	Oral cavity	OSCC	Fluid shear stress and atherosclerosis	92/3704	139/8465	6.51e-08	4.84e-07	2.47e-07	92
hsa049339	Oral cavity	OSCC	AGE-RAGE signaling pathway in diabetic complications	69/3704	100/8465	2.61e-07	1.65e-06	8.41e-07	69
hsa0467030	Oral cavity	OSCC	Leukocyte transendothelial migration	63/3704	114/8465	8.46e-03	1.96e-02	9.95e-03	63
hsa0466816	Oral cavity	OSCC	TNF signaling pathway	82/3704	114/8465	8.30e-10	9.59e-09	4.88e-09	82
hsa05418114	Oral cavity	OSCC	Fluid shear stress and atherosclerosis	92/3704	139/8465	6.51e-08	4.84e-07	2.47e-07	92
hsa0493316	Oral cavity	OSCC	AGE-RAGE signaling pathway in diabetic complications	69/3704	100/8465	2.61e-07	1.65e-06	8.41e-07	69
hsa04670113	Oral cavity	OSCC	Leukocyte transendothelial migration	63/3704	114/8465	8.46e-03	1.96e-02	9.95e-03	63
hsa0493361	Oral cavity	NEOLP	AGE-RAGE signaling pathway in diabetic complications	32/1112	100/8465	7.36e-07	9.10e-06	5.72e-06	32
hsa0541863	Oral cavity	NEOLP	Fluid shear stress and atherosclerosis	40/1112	139/8465	7.44e-07	9.10e-06	5.72e-06	40
hsa0467046	Oral cavity	NEOLP	Leukocyte transendothelial migration	31/1112	114/8465	4.39e-05	3.41e-04	2.14e-04	31
hsa0541763	Oral cavity	NEOLP	Lipid and atherosclerosis	47/1112	215/8465	2.39e-04	1.61e-03	1.01e-03	47

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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
ITGA4_ITGB1	VCAM1	ITGA4_ITGB1_VCAM1	VCAM	Breast	DCIS
ITGA4_ITGB7	VCAM1	ITGA4_ITGB7_VCAM1	VCAM	Breast	DCIS
ITGA4_ITGB1	VCAM1	ITGA4_ITGB1_VCAM1	VCAM	Cervix	CC
ITGA9_ITGB1	VCAM1	ITGA9_ITGB1_VCAM1	VCAM	Cervix	CC
ITGA4_ITGB1	VCAM1	ITGA4_ITGB1_VCAM1	VCAM	Cervix	Precancer
ITGA4_ITGB7	VCAM1	ITGA4_ITGB7_VCAM1	VCAM	Cervix	Precancer
ITGA4_ITGB1	VCAM1	ITGA4_ITGB1_VCAM1	VCAM	Esophagus	ESCC
ITGA9_ITGB1	VCAM1	ITGA9_ITGB1_VCAM1	VCAM	Esophagus	ESCC
ITGA4_ITGB1	VCAM1	ITGA4_ITGB1_VCAM1	VCAM	GC	ADJ
ITGA9_ITGB1	VCAM1	ITGA9_ITGB1_VCAM1	VCAM	GC	ADJ
ITGA9_ITGB1	VCAM1	ITGA9_ITGB1_VCAM1	VCAM	GC	GC
ITGA4_ITGB1	VCAM1	ITGA4_ITGB1_VCAM1	VCAM	HNSCC	ADJ
ITGA4_ITGB7	VCAM1	ITGA4_ITGB7_VCAM1	VCAM	HNSCC	ADJ
ITGA4_ITGB1	VCAM1	ITGA4_ITGB1_VCAM1	VCAM	HNSCC	Healthy
ITGA4_ITGB1	VCAM1	ITGA4_ITGB1_VCAM1	VCAM	HNSCC	OSCC
ITGA9_ITGB1	VCAM1	ITGA9_ITGB1_VCAM1	VCAM	HNSCC	OSCC
ITGA4_ITGB7	VCAM1	ITGA4_ITGB7_VCAM1	VCAM	HNSCC	OSCC
ITGA4_ITGB1	VCAM1	ITGA4_ITGB1_VCAM1	VCAM	HNSCC	Precancer
ITGA9_ITGB1	VCAM1	ITGA9_ITGB1_VCAM1	VCAM	HNSCC	Precancer
ITGA4_ITGB1	VCAM1	ITGA4_ITGB1_VCAM1	VCAM	Liver	HCC

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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

VCAM1

SNV

Missense_Mutation

rs190280671

c.1259N>G

p.Ser420Cys

p.S420C

P19320

protein_coding

deleterious(0)

benign(0.379)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

VCAM1

SNV

Missense_Mutation

novel

c.1157N>G

p.Thr386Ser

p.T386S

P19320

protein_coding

tolerated(0.15)

benign(0.048)

TCGA-A7-A6VX-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

VCAM1

SNV

Missense_Mutation

c.1941N>T

p.Lys647Asn

p.K647N

P19320

protein_coding

tolerated(0.19)

benign(0.049)

TCGA-A8-A08F-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

5-fluorouracil

VCAM1

SNV

Missense_Mutation

c.673N>T

p.Asn225Tyr

p.N225Y

P19320

protein_coding

deleterious(0)

probably_damaging(0.977)

TCGA-A8-A09E-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

VCAM1

SNV

Missense_Mutation

novel

c.1170G>T

p.Lys390Asn

p.K390N

P19320

protein_coding

tolerated(0.12)

possibly_damaging(0.685)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

VCAM1

SNV

Missense_Mutation

rs200879051

c.1967G>A

p.Arg656Gln

p.R656Q

P19320

protein_coding

tolerated(0.14)

benign(0.011)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

VCAM1

SNV

Missense_Mutation

novel

c.661N>C

p.Ile221Leu

p.I221L

P19320

protein_coding

tolerated(0.13)

benign(0.042)

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

VCAM1

SNV

Missense_Mutation

c.821C>A

p.Ala274Glu

p.A274E

P19320

protein_coding

tolerated(0.45)

probably_damaging(0.991)

TCGA-B6-A1KC-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

VCAM1

SNV

Missense_Mutation

c.1441C>T

p.Leu481Phe

p.L481F

P19320

protein_coding

deleterious(0.02)

probably_damaging(1)

TCGA-BH-A0HK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

VCAM1

SNV

Missense_Mutation

novel

c.1019N>T

p.Cys340Phe

p.C340F

P19320

protein_coding

tolerated(0.09)

probably_damaging(0.993)

TCGA-E2-A1LL-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

docetaxel

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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
7412	VCAM1	EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE, DRUGGABLE GENOME		TROGLITAZONE	TROGLITAZONE	10626906
7412	VCAM1	EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE, DRUGGABLE GENOME		PMA		7678355
7412	VCAM1	EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE, DRUGGABLE GENOME		PHORBOL MYRISTATE ACETATE		7678355
7412	VCAM1	EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE, DRUGGABLE GENOME		AGI-1067, SUCCINOBUCOL
7412	VCAM1	EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE, DRUGGABLE GENOME		6-MERCAPTOPURINE	MERCAPTOPURINE	7694584
7412	VCAM1	EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE, DRUGGABLE GENOME		DEXAMETHASONE	DEXAMETHASONE	7694584
7412	VCAM1	EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE, DRUGGABLE GENOME		CYCLOSPORINE	CYCLOSPORINE	7694584

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