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: ITGAV

Gene summary for ITGAV

Gene summary.

Gene information	Species	Human
	Gene symbol	ITGAV
	Gene ID	3685
	Gene name	integrin subunit alpha V
	Gene Alias	CD51
	Cytomap	2q32.1
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	P06756

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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
3685	ITGAV	CCI_2	Human	Cervix	CC	5.12e-09	1.05e+00	0.5249
3685	ITGAV	CCI_3	Human	Cervix	CC	4.61e-06	1.01e+00	0.516
3685	ITGAV	sample3	Human	Cervix	CC	1.71e-04	2.36e-01	0.1387
3685	ITGAV	T3	Human	Cervix	CC	1.42e-04	2.13e-01	0.1389
3685	ITGAV	LZE4T	Human	Esophagus	ESCC	2.43e-12	4.55e-01	0.0811
3685	ITGAV	LZE5T	Human	Esophagus	ESCC	2.40e-03	1.40e-01	0.0514
3685	ITGAV	LZE7T	Human	Esophagus	ESCC	3.53e-07	3.53e-01	0.0667
3685	ITGAV	LZE8T	Human	Esophagus	ESCC	1.41e-08	2.38e-01	0.067
3685	ITGAV	LZE20T	Human	Esophagus	ESCC	2.05e-03	2.69e-01	0.0662
3685	ITGAV	LZE22T	Human	Esophagus	ESCC	9.25e-04	8.36e-02	0.068
3685	ITGAV	LZE24T	Human	Esophagus	ESCC	6.96e-07	2.17e-01	0.0596
3685	ITGAV	P1T-E	Human	Esophagus	ESCC	1.64e-02	4.02e-01	0.0875
3685	ITGAV	P2T-E	Human	Esophagus	ESCC	9.04e-36	7.50e-01	0.1177
3685	ITGAV	P4T-E	Human	Esophagus	ESCC	5.31e-56	1.35e+00	0.1323
3685	ITGAV	P5T-E	Human	Esophagus	ESCC	5.10e-19	5.17e-01	0.1327
3685	ITGAV	P8T-E	Human	Esophagus	ESCC	9.16e-18	4.96e-01	0.0889
3685	ITGAV	P9T-E	Human	Esophagus	ESCC	1.97e-15	5.75e-01	0.1131
3685	ITGAV	P10T-E	Human	Esophagus	ESCC	1.43e-23	5.75e-01	0.116
3685	ITGAV	P11T-E	Human	Esophagus	ESCC	8.34e-09	6.39e-01	0.1426
3685	ITGAV	P12T-E	Human	Esophagus	ESCC	1.22e-34	7.90e-01	0.1122

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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
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:001603210	Cervix	CC	viral process	109/2311	415/18723	5.40e-15	6.46e-12	109
GO:200123310	Cervix	CC	regulation of apoptotic signaling pathway	96/2311	356/18723	4.08e-14	3.05e-11	96
GO:00315898	Cervix	CC	cell-substrate adhesion	96/2311	363/18723	1.48e-13	8.85e-11	96
GO:001905810	Cervix	CC	viral life cycle	87/2311	317/18723	2.20e-13	1.20e-10	87
GO:004578510	Cervix	CC	positive regulation of cell adhesion	101/2311	437/18723	1.96e-10	3.08e-08	101
GO:005212610	Cervix	CC	movement in host environment	52/2311	175/18723	7.03e-10	8.76e-08	52
GO:004440910	Cervix	CC	entry into host	47/2311	151/18723	8.45e-10	1.03e-07	47
GO:005170110	Cervix	CC	biological process involved in interaction with host	57/2311	203/18723	1.18e-09	1.41e-07	57
GO:00510566	Cervix	CC	regulation of small GTPase mediated signal transduction	75/2311	302/18723	1.54e-09	1.74e-07	75
GO:00512359	Cervix	CC	maintenance of location	78/2311	327/18723	5.18e-09	4.92e-07	78
GO:004671810	Cervix	CC	viral entry into host cell	44/2311	144/18723	5.47e-09	5.03e-07	44
GO:004440310	Cervix	CC	biological process involved in symbiotic interaction	71/2311	290/18723	7.94e-09	6.98e-07	71
GO:00071608	Cervix	CC	cell-matrix adhesion	60/2311	233/18723	1.58e-08	1.23e-06	60
GO:00072295	Cervix	CC	integrin-mediated signaling pathway	34/2311	107/18723	1.01e-07	5.25e-06	34
GO:200123410	Cervix	CC	negative regulation of apoptotic signaling pathway	56/2311	224/18723	1.39e-07	6.70e-06	56
GO:00344469	Cervix	CC	substrate adhesion-dependent cell spreading	32/2311	108/18723	1.36e-06	4.55e-05	32
GO:009719110	Cervix	CC	extrinsic apoptotic signaling pathway	52/2311	219/18723	2.06e-06	6.34e-05	52
GO:00068987	Cervix	CC	receptor-mediated endocytosis	53/2311	244/18723	2.52e-05	4.29e-04	53
GO:200123610	Cervix	CC	regulation of extrinsic apoptotic signaling pathway	37/2311	151/18723	2.80e-05	4.65e-04	37
GO:00301008	Cervix	CC	regulation of endocytosis	47/2311	211/18723	3.65e-05	5.82e-04	47

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0541820	Cervix	CC	Fluid shear stress and atherosclerosis	50/1267	139/8465	5.71e-10	1.32e-08	7.81e-09	50
hsa0516318	Cervix	CC	Human cytomegalovirus infection	65/1267	225/8465	4.59e-08	6.47e-07	3.83e-07	65
hsa0520516	Cervix	CC	Proteoglycans in cancer	60/1267	205/8465	9.13e-08	1.18e-06	7.00e-07	60
hsa0451010	Cervix	CC	Focal adhesion	59/1267	203/8465	1.53e-07	1.84e-06	1.09e-06	59
hsa0481016	Cervix	CC	Regulation of actin cytoskeleton	64/1267	229/8465	2.24e-07	2.59e-06	1.53e-06	64
hsa0414520	Cervix	CC	Phagosome	47/1267	152/8465	3.95e-07	4.26e-06	2.52e-06	47
hsa052226	Cervix	CC	Small cell lung cancer	29/1267	92/8465	4.38e-05	3.09e-04	1.83e-04	29
hsa051657	Cervix	CC	Human papillomavirus infection	74/1267	331/8465	1.70e-04	1.02e-03	6.03e-04	74
hsa0491918	Cervix	CC	Thyroid hormone signaling pathway	33/1267	121/8465	3.11e-04	1.65e-03	9.78e-04	33
hsa045147	Cervix	CC	Cell adhesion molecules	36/1267	157/8465	4.94e-03	1.67e-02	9.86e-03	36
hsa05418110	Cervix	CC	Fluid shear stress and atherosclerosis	50/1267	139/8465	5.71e-10	1.32e-08	7.81e-09	50
hsa0516319	Cervix	CC	Human cytomegalovirus infection	65/1267	225/8465	4.59e-08	6.47e-07	3.83e-07	65
hsa0520517	Cervix	CC	Proteoglycans in cancer	60/1267	205/8465	9.13e-08	1.18e-06	7.00e-07	60
hsa0451014	Cervix	CC	Focal adhesion	59/1267	203/8465	1.53e-07	1.84e-06	1.09e-06	59
hsa0481017	Cervix	CC	Regulation of actin cytoskeleton	64/1267	229/8465	2.24e-07	2.59e-06	1.53e-06	64
hsa04145110	Cervix	CC	Phagosome	47/1267	152/8465	3.95e-07	4.26e-06	2.52e-06	47
hsa0522213	Cervix	CC	Small cell lung cancer	29/1267	92/8465	4.38e-05	3.09e-04	1.83e-04	29
hsa0516512	Cervix	CC	Human papillomavirus infection	74/1267	331/8465	1.70e-04	1.02e-03	6.03e-04	74
hsa0491919	Cervix	CC	Thyroid hormone signaling pathway	33/1267	121/8465	3.11e-04	1.65e-03	9.78e-04	33
hsa0451412	Cervix	CC	Cell adhesion molecules	36/1267	157/8465	4.94e-03	1.67e-02	9.86e-03	36

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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
SPP1	ITGAV_ITGB1	SPP1_ITGAV_ITGB1	SPP1	Breast	DCIS
SPP1	ITGAV_ITGB5	SPP1_ITGAV_ITGB5	SPP1	Breast	DCIS
FN1	ITGAV_ITGB1	FN1_ITGAV_ITGB1	FN1	Breast	DCIS
JAM2	ITGAV_ITGB1	JAM2_ITGAV_ITGB1	JAM	Breast	DCIS
POSTN	ITGAV_ITGB5	POSTN_ITGAV_ITGB5	PERIOSTIN	Breast	DCIS
COL1A1	ITGAV_ITGB8	COL1A1_ITGAV_ITGB8	COLLAGEN	Breast	Healthy
COL1A2	ITGAV_ITGB8	COL1A2_ITGAV_ITGB8	COLLAGEN	Breast	Healthy
COL4A1	ITGAV_ITGB8	COL4A1_ITGAV_ITGB8	COLLAGEN	Breast	Healthy
COL4A2	ITGAV_ITGB8	COL4A2_ITGAV_ITGB8	COLLAGEN	Breast	Healthy
COL6A1	ITGAV_ITGB8	COL6A1_ITGAV_ITGB8	COLLAGEN	Breast	Healthy
COL6A2	ITGAV_ITGB8	COL6A2_ITGAV_ITGB8	COLLAGEN	Breast	Healthy
COL6A3	ITGAV_ITGB8	COL6A3_ITGAV_ITGB8	COLLAGEN	Breast	Healthy
LAMA2	ITGAV_ITGB8	LAMA2_ITGAV_ITGB8	LAMININ	Breast	Healthy
LAMA3	ITGAV_ITGB8	LAMA3_ITGAV_ITGB8	LAMININ	Breast	Healthy
LAMA4	ITGAV_ITGB8	LAMA4_ITGAV_ITGB8	LAMININ	Breast	Healthy
LAMB1	ITGAV_ITGB8	LAMB1_ITGAV_ITGB8	LAMININ	Breast	Healthy
LAMB2	ITGAV_ITGB8	LAMB2_ITGAV_ITGB8	LAMININ	Breast	Healthy
LAMB3	ITGAV_ITGB8	LAMB3_ITGAV_ITGB8	LAMININ	Breast	Healthy
LAMC1	ITGAV_ITGB8	LAMC1_ITGAV_ITGB8	LAMININ	Breast	Healthy
LAMC2	ITGAV_ITGB8	LAMC2_ITGAV_ITGB8	LAMININ	Breast	Healthy

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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

ITGAV

SNV

Missense_Mutation

c.1264G>A

p.Glu422Lys

p.E422K

P06756

protein_coding

tolerated(0.45)

benign(0.003)

TCGA-A8-A06Q-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

ITGAV

SNV

Missense_Mutation

c.2729N>G

p.Leu910Trp

p.L910W

P06756

protein_coding

tolerated(0.3)

probably_damaging(0.997)

TCGA-A8-A081-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ITGAV

SNV

Missense_Mutation

c.147N>G

p.Phe49Leu

p.F49L

P06756

protein_coding

deleterious(0.02)

probably_damaging(0.97)

TCGA-A8-A0AD-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

ITGAV

SNV

Missense_Mutation

c.323G>C

p.Arg108Thr

p.R108T

P06756

protein_coding

deleterious(0.02)

benign(0.179)

TCGA-BH-A0W7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

ITGAV

SNV

Missense_Mutation

c.2281T>C

p.Ser761Pro

p.S761P

P06756

protein_coding

tolerated(0.12)

probably_damaging(0.915)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ITGAV

SNV

Missense_Mutation

rs200733186

c.2834N>G

p.Asn945Ser

p.N945S

P06756

protein_coding

deleterious(0.04)

probably_damaging(0.991)

TCGA-OL-A97C-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ITGAV

deletion

Frame_Shift_Del

c.1682delG

p.Gly561AspfsTer2

p.G561Dfs*2

P06756

protein_coding

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ITGAV

SNV

Missense_Mutation

c.1990N>G

p.Gln664Glu

p.Q664E

P06756

protein_coding

tolerated(1)

benign(0.224)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

ITGAV

SNV

Missense_Mutation

rs201231113

c.298A>G

p.Ile100Val

p.I100V

P06756

protein_coding

tolerated(0.12)

benign(0)

TCGA-ZJ-AAXT-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

ITGAV

SNV

Missense_Mutation

rs554897868

c.2120N>A

p.Arg707His

p.R707H

P06756

protein_coding

deleterious(0.01)

benign(0.028)

TCGA-4T-AA8H-01

Colorectum

colon adenocarcinoma

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
3685	ITGAV	DRUGGABLE GENOME, CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE	inhibitor	CHEMBL2109621	ABITUZUMAB
3685	ITGAV	DRUGGABLE GENOME, CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE	antagonist	348353648
3685	ITGAV	DRUGGABLE GENOME, CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE	antagonist	CHEMBL429876	CILENGITIDE
3685	ITGAV	DRUGGABLE GENOME, CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE		VOLOCIXIMAB	VOLOCIXIMAB
3685	ITGAV	DRUGGABLE GENOME, CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE		CYPATE	CYPATE	22871580
3685	ITGAV	DRUGGABLE GENOME, CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE		GLPG0187	GLPG-0187
3685	ITGAV	DRUGGABLE GENOME, CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE		CNTO-95	INTETUMUMAB
3685	ITGAV	DRUGGABLE GENOME, CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE	inhibitor	CHEMBL2109623	STX-100
3685	ITGAV	DRUGGABLE GENOME, CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE		Abituzumab	ABITUZUMAB
3685	ITGAV	DRUGGABLE GENOME, CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE		CILENGITIDE	CILENGITIDE	24095096

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