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: ITGB5

Gene summary for ITGB5

Gene summary.

Gene information	Species	Human
	Gene symbol	ITGB5
	Gene ID	3693
	Gene name	integrin subunit beta 5
	Gene Alias	ITGB5
	Cytomap	3q21.2
	Gene Type	protein-coding
	GO ID	GO:0001704
	UniProtAcc	L7RT22

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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
3693	ITGB5	LZE4T	Human	Esophagus	ESCC	1.13e-03	-8.40e-02	0.0811
3693	ITGB5	LZE7T	Human	Esophagus	ESCC	8.32e-09	1.42e-01	0.0667
3693	ITGB5	LZE24T	Human	Esophagus	ESCC	5.40e-06	-5.49e-02	0.0596
3693	ITGB5	P2T-E	Human	Esophagus	ESCC	2.39e-12	-7.57e-02	0.1177
3693	ITGB5	P4T-E	Human	Esophagus	ESCC	5.44e-06	4.73e-02	0.1323
3693	ITGB5	P8T-E	Human	Esophagus	ESCC	2.27e-12	3.04e-01	0.0889
3693	ITGB5	P9T-E	Human	Esophagus	ESCC	9.33e-04	2.37e-01	0.1131
3693	ITGB5	P12T-E	Human	Esophagus	ESCC	8.74e-16	1.04e-01	0.1122
3693	ITGB5	P15T-E	Human	Esophagus	ESCC	7.87e-05	1.55e-01	0.1149
3693	ITGB5	P16T-E	Human	Esophagus	ESCC	2.78e-17	9.57e-02	0.1153
3693	ITGB5	P17T-E	Human	Esophagus	ESCC	8.93e-04	-1.92e-02	0.1278
3693	ITGB5	P20T-E	Human	Esophagus	ESCC	1.28e-05	1.26e-02	0.1124
3693	ITGB5	P21T-E	Human	Esophagus	ESCC	3.24e-13	8.24e-02	0.1617
3693	ITGB5	P22T-E	Human	Esophagus	ESCC	9.54e-24	8.79e-02	0.1236
3693	ITGB5	P23T-E	Human	Esophagus	ESCC	8.89e-13	3.04e-02	0.108
3693	ITGB5	P24T-E	Human	Esophagus	ESCC	2.24e-09	-5.33e-02	0.1287
3693	ITGB5	P26T-E	Human	Esophagus	ESCC	6.16e-29	3.39e-02	0.1276
3693	ITGB5	P27T-E	Human	Esophagus	ESCC	2.78e-10	1.65e-01	0.1055
3693	ITGB5	P28T-E	Human	Esophagus	ESCC	1.61e-13	1.91e-01	0.1149
3693	ITGB5	P30T-E	Human	Esophagus	ESCC	1.66e-04	3.64e-01	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
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:0016032111	Esophagus	ESCC	viral process	301/8552	415/18723	3.34e-29	1.32e-26	301
GO:0019058111	Esophagus	ESCC	viral life cycle	226/8552	317/18723	1.17e-20	1.76e-18	226
GO:0044403111	Esophagus	ESCC	biological process involved in symbiotic interaction	186/8552	290/18723	1.43e-10	4.16e-09	186
GO:0051701111	Esophagus	ESCC	biological process involved in interaction with host	135/8552	203/18723	1.49e-09	3.49e-08	135
GO:003158919	Esophagus	ESCC	cell-substrate adhesion	221/8552	363/18723	3.06e-09	6.62e-08	221
GO:0052126111	Esophagus	ESCC	movement in host environment	117/8552	175/18723	1.14e-08	2.26e-07	117
GO:000701527	Esophagus	ESCC	actin filament organization	259/8552	442/18723	2.37e-08	4.50e-07	259
GO:00715599	Esophagus	ESCC	response to transforming growth factor beta	157/8552	256/18723	2.95e-07	4.23e-06	157
GO:00715609	Esophagus	ESCC	cellular response to transforming growth factor beta stimulus	151/8552	250/18723	1.78e-06	2.10e-05	151
GO:000716018	Esophagus	ESCC	cell-matrix adhesion	141/8552	233/18723	3.33e-06	3.71e-05	141
GO:005101727	Esophagus	ESCC	actin filament bundle assembly	100/8552	157/18723	3.87e-06	4.17e-05	100
GO:00073698	Esophagus	ESCC	gastrulation	115/8552	185/18723	4.35e-06	4.64e-05	115
GO:0044409111	Esophagus	ESCC	entry into host	96/8552	151/18723	6.73e-06	6.84e-05	96
GO:00071799	Esophagus	ESCC	transforming growth factor beta receptor signaling pathway	121/8552	198/18723	8.26e-06	8.03e-05	121
GO:006157227	Esophagus	ESCC	actin filament bundle organization	101/8552	161/18723	9.22e-06	8.82e-05	101
GO:00074926	Esophagus	ESCC	endoderm development	54/8552	77/18723	1.20e-05	1.12e-04	54
GO:004671827	Esophagus	ESCC	viral entry into host cell	89/8552	144/18723	6.84e-05	5.18e-04	89
GO:003003820	Esophagus	ESCC	contractile actin filament bundle assembly	67/8552	106/18723	2.03e-04	1.28e-03	67
GO:004314920	Esophagus	ESCC	stress fiber assembly	67/8552	106/18723	2.03e-04	1.28e-03	67
GO:00017064	Esophagus	ESCC	endoderm formation	38/8552	54/18723	2.08e-04	1.31e-03	38

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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
hsa0520529	Esophagus	ESCC	Proteoglycans in cancer	138/4205	205/8465	1.79e-07	1.40e-06	7.15e-07	138
hsa0414530	Esophagus	ESCC	Phagosome	100/4205	152/8465	3.81e-05	1.72e-04	8.82e-05	100
hsa0451020	Esophagus	ESCC	Focal adhesion	127/4205	203/8465	1.25e-04	4.99e-04	2.56e-04	127
hsa0481028	Esophagus	ESCC	Regulation of actin cytoskeleton	133/4205	229/8465	5.94e-03	1.48e-02	7.56e-03	133
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
hsa0520537	Esophagus	ESCC	Proteoglycans in cancer	138/4205	205/8465	1.79e-07	1.40e-06	7.15e-07	138
hsa04145114	Esophagus	ESCC	Phagosome	100/4205	152/8465	3.81e-05	1.72e-04	8.82e-05	100
hsa04510111	Esophagus	ESCC	Focal adhesion	127/4205	203/8465	1.25e-04	4.99e-04	2.56e-04	127
hsa04810112	Esophagus	ESCC	Regulation of actin cytoskeleton	133/4205	229/8465	5.94e-03	1.48e-02	7.56e-03	133
hsa0415114	Esophagus	ESCC	PI3K-Akt signaling pathway	197/4205	354/8465	1.24e-02	2.83e-02	1.45e-02	197
hsa0481010	Liver	NAFLD	Regulation of actin cytoskeleton	50/1043	229/8465	3.01e-05	7.59e-04	6.11e-04	50
hsa045106	Liver	NAFLD	Focal adhesion	38/1043	203/8465	5.13e-03	4.43e-02	3.57e-02	38
hsa0481011	Liver	NAFLD	Regulation of actin cytoskeleton	50/1043	229/8465	3.01e-05	7.59e-04	6.11e-04	50
hsa0451011	Liver	NAFLD	Focal adhesion	38/1043	203/8465	5.13e-03	4.43e-02	3.57e-02	38
hsa0451021	Liver	Cirrhotic	Focal adhesion	93/2530	203/8465	9.27e-07	1.10e-05	6.80e-06	93
hsa0414514	Liver	Cirrhotic	Phagosome	73/2530	152/8465	1.61e-06	1.78e-05	1.10e-05	73
hsa0481021	Liver	Cirrhotic	Regulation of actin cytoskeleton	100/2530	229/8465	5.28e-06	5.50e-05	3.39e-05	100
hsa0520510	Liver	Cirrhotic	Proteoglycans in cancer	85/2530	205/8465	2.37e-04	1.58e-03	9.75e-04	85

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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_ITGB5	SPP1_ITGAV_ITGB5	SPP1	Breast	DCIS
POSTN	ITGAV_ITGB5	POSTN_ITGAV_ITGB5	PERIOSTIN	Breast	DCIS
POSTN	ITGAV_ITGB5	POSTN_ITGAV_ITGB5	PERIOSTIN	Breast	IDC
SPP1	ITGAV_ITGB5	SPP1_ITGAV_ITGB5	SPP1	Cervix	CC
SPP1	ITGAV_ITGB5	SPP1_ITGAV_ITGB5	SPP1	Cervix	Healthy
SPP1	ITGAV_ITGB5	SPP1_ITGAV_ITGB5	SPP1	Cervix	Precancer
SPP1	ITGAV_ITGB5	SPP1_ITGAV_ITGB5	SPP1	CRC	MSI-H
SPP1	ITGAV_ITGB5	SPP1_ITGAV_ITGB5	SPP1	Endometrium	AEH
SPP1	ITGAV_ITGB5	SPP1_ITGAV_ITGB5	SPP1	Endometrium	EEC
SPP1	ITGAV_ITGB5	SPP1_ITGAV_ITGB5	SPP1	Endometrium	Healthy
POSTN	ITGAV_ITGB5	POSTN_ITGAV_ITGB5	PERIOSTIN	Endometrium	Healthy
POSTN	ITGAV_ITGB5	POSTN_ITGAV_ITGB5	PERIOSTIN	Esophagus	ESCC
POSTN	ITGAV_ITGB5	POSTN_ITGAV_ITGB5	PERIOSTIN	HNSCC	Healthy
POSTN	ITGAV_ITGB5	POSTN_ITGAV_ITGB5	PERIOSTIN	HNSCC	OSCC
POSTN	ITGAV_ITGB5	POSTN_ITGAV_ITGB5	PERIOSTIN	HNSCC	Precancer
VTN	ITGAV_ITGB5	VTN_ITGAV_ITGB5	VTN	Liver	Healthy
SPP1	ITGAV_ITGB5	SPP1_ITGAV_ITGB5	SPP1	Liver	Healthy
SPP1	ITGAV_ITGB5	SPP1_ITGAV_ITGB5	SPP1	Liver	Precancer
VTN	ITGAV_ITGB5	VTN_ITGAV_ITGB5	VTN	Liver	Precancer
POSTN	ITGAV_ITGB5	POSTN_ITGAV_ITGB5	PERIOSTIN	Lung	IAC

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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

ITGB5

SNV

Missense_Mutation

c.1121N>A

p.Ala374Glu

p.A374E

P18084

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-A2-A4S2-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

ITGB5

SNV

Missense_Mutation

c.677G>C

p.Arg226Thr

p.R226T

P18084

protein_coding

deleterious(0.03)

benign(0.229)

TCGA-A8-A09G-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

ITGB5

SNV

Missense_Mutation

c.833A>G

p.Asp278Gly

p.D278G

P18084

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-BH-A0DP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

ITGB5

SNV

Missense_Mutation

c.589N>C

p.Tyr197His

p.Y197H

P18084

protein_coding

tolerated(0.27)

probably_damaging(0.999)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

ITGB5

insertion

Frame_Shift_Ins

novel

c.1590_1591insCTCCCAGGTTCAAGCAATTCTCC

p.Asn531LeufsTer143

p.N531Lfs*143

P18084

protein_coding

TCGA-A8-A09A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

ITGB5

insertion

Frame_Shift_Ins

novel

c.683_684insAA

p.Asp228GlufsTer76

p.D228Efs*76

P18084

protein_coding

TCGA-AO-A03R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

ITGB5

insertion

Frame_Shift_Ins

novel

c.681_682insAAACCCTGTCTCTACT

p.Asp228LysfsTer6

p.D228Kfs*6

P18084

protein_coding

TCGA-AO-A03R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

ITGB5

insertion

In_Frame_Ins

novel

c.448_449insCCTGGCTGATTTTTGTATTTTTAGTAGAGATGGGGTTTC

p.Met150delinsThrTrpLeuIlePheValPheLeuValGluMetGlyPheLeu

p.M150delinsTWLIFVFLVEMGFL

P18084

protein_coding

TCGA-AO-A03R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

ITGB5

insertion

Nonsense_Mutation

novel

c.402_403insTTTCTTTAAATGTCAAGATTATGCAAGTGACTGCAGTGAGT

p.Asp135PhefsTer3

p.D135Ffs*3

P18084

protein_coding

TCGA-BH-A0B8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

ITGB5

SNV

Missense_Mutation

novel

c.991A>G

p.Ile331Val

p.I331V

P18084

protein_coding

tolerated(0.13)

probably_damaging(0.99)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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
3693	ITGB5	CELL SURFACE, DRUGGABLE GENOME		CNTO-95	INTETUMUMAB
3693	ITGB5	CELL SURFACE, DRUGGABLE GENOME	inhibitor	CILENGITIDE	CILENGITIDE
3693	ITGB5	CELL SURFACE, DRUGGABLE GENOME	inhibitor	CHEMBL2109621	ABITUZUMAB
3693	ITGB5	CELL SURFACE, DRUGGABLE GENOME	inhibitor	385612210
3693	ITGB5	CELL SURFACE, DRUGGABLE GENOME		CILENGITIDE	CILENGITIDE
3693	ITGB5	CELL SURFACE, DRUGGABLE GENOME	antagonist	CHEMBL429876	CILENGITIDE
3693	ITGB5	CELL SURFACE, DRUGGABLE GENOME	antagonist	CHEMBL1743032	INTETUMUMAB
3693	ITGB5	CELL SURFACE, DRUGGABLE GENOME		GLPG0187	GLPG-0187

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