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: ITGB6

Gene summary for ITGB6

Gene summary.

Gene information	Species	Human
	Gene symbol	ITGB6
	Gene ID	3694
	Gene name	integrin subunit beta 6
	Gene Alias	AI1H
	Cytomap	2q24.2
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	P18564

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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
3694	ITGB6	CCI_2	Human	Cervix	CC	5.22e-10	1.20e+00	0.5249
3694	ITGB6	CCI_3	Human	Cervix	CC	3.15e-15	1.00e+00	0.516
3694	ITGB6	Tumor	Human	Cervix	CC	7.28e-12	4.07e-01	0.1241
3694	ITGB6	sample1	Human	Cervix	CC	2.25e-03	3.02e-01	0.0959
3694	ITGB6	sample3	Human	Cervix	CC	3.03e-18	4.71e-01	0.1387
3694	ITGB6	T1	Human	Cervix	CC	1.15e-16	4.75e-01	0.0918
3694	ITGB6	T3	Human	Cervix	CC	1.06e-16	4.82e-01	0.1389
3694	ITGB6	P1T-E	Human	Esophagus	ESCC	4.08e-02	2.53e-01	0.0875
3694	ITGB6	P2T-E	Human	Esophagus	ESCC	1.10e-49	1.06e+00	0.1177
3694	ITGB6	P4T-E	Human	Esophagus	ESCC	4.71e-02	1.84e-01	0.1323
3694	ITGB6	P5T-E	Human	Esophagus	ESCC	2.39e-12	1.86e-01	0.1327
3694	ITGB6	P8T-E	Human	Esophagus	ESCC	1.02e-09	1.61e-01	0.0889
3694	ITGB6	P11T-E	Human	Esophagus	ESCC	7.60e-16	1.47e+00	0.1426
3694	ITGB6	P20T-E	Human	Esophagus	ESCC	8.81e-24	1.04e+00	0.1124
3694	ITGB6	P21T-E	Human	Esophagus	ESCC	1.15e-09	3.31e-01	0.1617
3694	ITGB6	P23T-E	Human	Esophagus	ESCC	8.15e-14	5.67e-01	0.108
3694	ITGB6	P24T-E	Human	Esophagus	ESCC	2.37e-31	1.25e+00	0.1287
3694	ITGB6	P26T-E	Human	Esophagus	ESCC	2.09e-13	7.13e-02	0.1276
3694	ITGB6	P36T-E	Human	Esophagus	ESCC	3.53e-22	1.46e+00	0.1187
3694	ITGB6	P37T-E	Human	Esophagus	ESCC	1.18e-22	7.63e-01	0.1371

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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
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

∗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:004206010	Cervix	CC	wound healing	109/2311	422/18723	1.84e-14	1.57e-11	109
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:00435884	Cervix	CC	skin development	71/2311	263/18723	8.04e-11	1.46e-08	71
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: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:003009910	Cervix	CC	myeloid cell differentiation	83/2311	381/18723	1.31e-07	6.42e-06	83
GO:00712148	Cervix	CC	cellular response to abiotic stimulus	69/2311	331/18723	7.36e-06	1.73e-04	69
GO:01040048	Cervix	CC	cellular response to environmental stimulus	69/2311	331/18723	7.36e-06	1.73e-04	69
GO:00096158	Cervix	CC	response to virus	73/2311	367/18723	2.22e-05	3.95e-04	73
GO:00018949	Cervix	CC	tissue homeostasis	57/2311	268/18723	2.43e-05	4.21e-04	57
GO:00025738	Cervix	CC	myeloid leukocyte differentiation	47/2311	208/18723	2.48e-05	4.27e-04	47
GO:00714798	Cervix	CC	cellular response to ionizing radiation	22/2311	72/18723	3.47e-05	5.60e-04	22
GO:00093149	Cervix	CC	response to radiation	86/2311	456/18723	3.50e-05	5.63e-04	86

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
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
hsa051657	Cervix	CC	Human papillomavirus infection	74/1267	331/8465	1.70e-04	1.02e-03	6.03e-04	74
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
hsa0516512	Cervix	CC	Human papillomavirus infection	74/1267	331/8465	1.70e-04	1.02e-03	6.03e-04	74
hsa0516510	Esophagus	ESCC	Human papillomavirus infection	215/4205	331/8465	7.86e-09	7.12e-08	3.65e-08	215
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
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
hsa045108	Lung	IAC	Focal adhesion	59/1053	203/8465	1.31e-10	1.06e-08	7.06e-09	59
hsa051656	Lung	IAC	Human papillomavirus infection	71/1053	331/8465	1.88e-06	7.63e-05	5.06e-05	71
hsa0481012	Lung	IAC	Regulation of actin cytoskeleton	49/1053	229/8465	7.94e-05	1.17e-03	7.79e-04	49
hsa054126	Lung	IAC	Arrhythmogenic right ventricular cardiomyopathy	22/1053	77/8465	1.15e-04	1.49e-03	9.88e-04	22
hsa04512	Lung	IAC	ECM-receptor interaction	20/1053	89/8465	5.65e-03	2.45e-02	1.63e-02	20
hsa05410	Lung	IAC	Hypertrophic cardiomyopathy	20/1053	90/8465	6.44e-03	2.68e-02	1.78e-02	20

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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
FN1	ITGAV_ITGB6	FN1_ITGAV_ITGB6	FN1	Breast	Healthy
TNC	ITGAV_ITGB6	TNC_ITGAV_ITGB6	TENASCIN	Breast	Healthy
TNXB	ITGAV_ITGB6	TNXB_ITGAV_ITGB6	TENASCIN	Breast	Healthy
FN1	ITGAV_ITGB6	FN1_ITGAV_ITGB6	FN1	Cervix	CC
SPP1	ITGAV_ITGB6	SPP1_ITGAV_ITGB6	SPP1	Cervix	CC
TNC	ITGAV_ITGB6	TNC_ITGAV_ITGB6	TENASCIN	Cervix	CC
TNXB	ITGAV_ITGB6	TNXB_ITGAV_ITGB6	TENASCIN	Cervix	CC
FN1	ITGAV_ITGB6	FN1_ITGAV_ITGB6	FN1	CRC	ADJ
TNXB	ITGAV_ITGB6	TNXB_ITGAV_ITGB6	TENASCIN	CRC	ADJ
TNXB	ITGAV_ITGB6	TNXB_ITGAV_ITGB6	TENASCIN	CRC	FAP
TNC	ITGAV_ITGB6	TNC_ITGAV_ITGB6	TENASCIN	Esophagus	ESCC
TNXB	ITGAV_ITGB6	TNXB_ITGAV_ITGB6	TENASCIN	Esophagus	ESCC
FN1	ITGAV_ITGB6	FN1_ITGAV_ITGB6	FN1	HNSCC	OSCC
TNC	ITGAV_ITGB6	TNC_ITGAV_ITGB6	TENASCIN	HNSCC	OSCC
TNXB	ITGAV_ITGB6	TNXB_ITGAV_ITGB6	TENASCIN	HNSCC	OSCC
FN1	ITGAV_ITGB6	FN1_ITGAV_ITGB6	FN1	HNSCC	Precancer
TNC	ITGAV_ITGB6	TNC_ITGAV_ITGB6	TENASCIN	HNSCC	Precancer
TNXB	ITGAV_ITGB6	TNXB_ITGAV_ITGB6	TENASCIN	HNSCC	Precancer
FN1	ITGAV_ITGB6	FN1_ITGAV_ITGB6	FN1	Lung	IAC
TNC	ITGAV_ITGB6	TNC_ITGAV_ITGB6	TENASCIN	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

ITGB6

SNV

Missense_Mutation

novel

c.1727N>T

p.Cys576Phe

p.C576F

P18564

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A2-A4S1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ITGB6

SNV

Missense_Mutation

rs756187131

c.1754N>T

p.Ser585Phe

p.S585F

P18564

protein_coding

deleterious(0)

probably_damaging(0.91)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ITGB6

SNV

Missense_Mutation

c.1212N>C

p.Lys404Asn

p.K404N

P18564

protein_coding

deleterious(0)

possibly_damaging(0.903)

TCGA-BH-A0DZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

ITGB6

SNV

Missense_Mutation

rs552791527

c.1916G>A

p.Gly639Asp

p.G639D

P18564

protein_coding

tolerated(0.22)

benign(0.001)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ITGB6

SNV

Missense_Mutation

rs760815776

c.2344N>A

p.Val782Ile

p.V782I

P18564

protein_coding

tolerated_low_confidence(0.44)

benign(0)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ITGB6

SNV

Missense_Mutation

novel

c.716C>A

p.Pro239His

p.P239H

P18564

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-E2-A1LE-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

herceptin

ITGB6

SNV

Missense_Mutation

rs376329044

c.1910N>T

p.Ala637Val

p.A637V

P18564

protein_coding

tolerated(0.22)

benign(0.174)

TCGA-E9-A1NG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

ITGB6

insertion

Nonsense_Mutation

novel

c.889_890insATATCAGTGAGGATAGCCGCATGTTGTCTTTTAGTCAGTGAGGG

p.Ser297AsnfsTer14

p.S297Nfs*14

P18564

protein_coding

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

ITGB6

insertion

Nonsense_Mutation

novel

c.471_472insACACATTATGCAGGTGATGGTGGAGGACAGATTGCTTTGTGA

p.Ser157_Arg158insThrHisTyrAlaGlyAspGlyGlyGlyGlnIleAlaLeuTer

p.S157_R158insTHYAGDGGGQIAL*

P18564

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ITGB6

SNV

Missense_Mutation

rs751132914

c.821N>G

p.Ser274Cys

p.S274C

P18564

protein_coding

deleterious(0.04)

probably_damaging(0.999)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

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
3694	ITGB6	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE	inhibitor	385612210
3694	ITGB6	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE	inhibitor	CHEMBL2109623	STX-100
3694	ITGB6	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE	antagonist	CHEMBL1743032	INTETUMUMAB
3694	ITGB6	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE		GLPG0187	GLPG-0187
3694	ITGB6	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE	inhibitor	CHEMBL2109621	ABITUZUMAB

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