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: ITGA1

Gene summary for ITGA1

Gene summary.

Gene information	Species	Human
	Gene symbol	ITGA1
	Gene ID	3672
	Gene name	integrin subunit alpha 1
	Gene Alias	CD49a
	Cytomap	5q11.2
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	P56199

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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
3672	ITGA1	LZE6T	Human	Esophagus	ESCC	3.74e-05	2.01e-01	0.0845
3672	ITGA1	P8T-E	Human	Esophagus	ESCC	1.63e-02	9.15e-02	0.0889
3672	ITGA1	P9T-E	Human	Esophagus	ESCC	1.90e-02	2.02e-01	0.1131
3672	ITGA1	P11T-E	Human	Esophagus	ESCC	1.89e-08	6.87e-01	0.1426
3672	ITGA1	P12T-E	Human	Esophagus	ESCC	3.94e-04	2.00e-01	0.1122
3672	ITGA1	P19T-E	Human	Esophagus	ESCC	3.71e-14	1.39e+00	0.1662
3672	ITGA1	P32T-E	Human	Esophagus	ESCC	5.22e-04	1.66e-01	0.1666
3672	ITGA1	P44T-E	Human	Esophagus	ESCC	8.48e-07	4.20e-01	0.1096
3672	ITGA1	P75T-E	Human	Esophagus	ESCC	4.57e-04	6.19e-02	0.1125
3672	ITGA1	NAFLD1	Human	Liver	NAFLD	3.07e-12	1.04e+00	-0.04
3672	ITGA1	S41	Human	Liver	Cirrhotic	1.46e-06	6.26e-01	-0.0343
3672	ITGA1	S43	Human	Liver	Cirrhotic	6.98e-08	2.30e-01	-0.0187
3672	ITGA1	HCC1_Meng	Human	Liver	HCC	4.23e-82	1.58e-01	0.0246
3672	ITGA1	HCC2_Meng	Human	Liver	HCC	3.32e-10	-9.04e-02	0.0107
3672	ITGA1	Pt13.b	Human	Liver	HCC	1.21e-20	5.43e-01	0.0251
3672	ITGA1	S014	Human	Liver	HCC	1.87e-13	8.96e-01	0.2254
3672	ITGA1	S015	Human	Liver	HCC	5.16e-17	1.13e+00	0.2375
3672	ITGA1	S016	Human	Liver	HCC	2.94e-16	8.41e-01	0.2243
3672	ITGA1	S028	Human	Liver	HCC	3.71e-02	2.60e-01	0.2503
3672	ITGA1	S029	Human	Liver	HCC	1.52e-05	5.52e-01	0.2581

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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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:001631110	Esophagus	ESCC	dephosphorylation	251/8552	417/18723	1.26e-09	2.99e-08	251
GO:003158919	Esophagus	ESCC	cell-substrate adhesion	221/8552	363/18723	3.06e-09	6.62e-08	221
GO:000647018	Esophagus	ESCC	protein dephosphorylation	177/8552	281/18723	3.13e-09	6.72e-08	177
GO:0070997111	Esophagus	ESCC	neuron death	216/8552	361/18723	3.49e-08	6.45e-07	216
GO:0035304111	Esophagus	ESCC	regulation of protein dephosphorylation	66/8552	90/18723	8.82e-08	1.48e-06	66
GO:0035303111	Esophagus	ESCC	regulation of dephosphorylation	88/8552	128/18723	1.04e-07	1.71e-06	88
GO:003812718	Esophagus	ESCC	ERBB signaling pathway	82/8552	121/18723	7.23e-07	9.40e-06	82
GO:0051402110	Esophagus	ESCC	neuron apoptotic process	148/8552	246/18723	3.08e-06	3.47e-05	148
GO:000716018	Esophagus	ESCC	cell-matrix adhesion	141/8552	233/18723	3.33e-06	3.71e-05	141
GO:1901214111	Esophagus	ESCC	regulation of neuron death	186/8552	319/18723	3.35e-06	3.73e-05	186
GO:000717318	Esophagus	ESCC	epidermal growth factor receptor signaling pathway	73/8552	108/18723	3.36e-06	3.73e-05	73
GO:1901216111	Esophagus	ESCC	positive regulation of neuron death	65/8552	97/18723	1.76e-05	1.56e-04	65
GO:190118413	Esophagus	ESCC	regulation of ERBB signaling pathway	54/8552	79/18723	3.81e-05	3.08e-04	54
GO:00420588	Esophagus	ESCC	regulation of epidermal growth factor receptor signaling pathway	50/8552	73/18723	6.75e-05	5.12e-04	50
GO:19011859	Esophagus	ESCC	negative regulation of ERBB signaling pathway	25/8552	32/18723	1.84e-04	1.17e-03	25
GO:0043525110	Esophagus	ESCC	positive regulation of neuron apoptotic process	40/8552	58/18723	2.83e-04	1.71e-03	40
GO:0043666110	Esophagus	ESCC	regulation of phosphoprotein phosphatase activity	40/8552	58/18723	2.83e-04	1.71e-03	40
GO:00072299	Esophagus	ESCC	integrin-mediated signaling pathway	67/8552	107/18723	3.03e-04	1.81e-03	67
GO:004352317	Esophagus	ESCC	regulation of neuron apoptotic process	122/8552	212/18723	3.21e-04	1.90e-03	122
GO:00420599	Esophagus	ESCC	negative regulation of epidermal growth factor receptor signaling pathway	22/8552	28/18723	3.95e-04	2.26e-03	22

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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
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
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
hsa0481021	Liver	Cirrhotic	Regulation of actin cytoskeleton	100/2530	229/8465	5.28e-06	5.50e-05	3.39e-05	100
hsa05165	Liver	Cirrhotic	Human papillomavirus infection	124/2530	331/8465	1.55e-03	7.83e-03	4.83e-03	124
hsa0451031	Liver	Cirrhotic	Focal adhesion	93/2530	203/8465	9.27e-07	1.10e-05	6.80e-06	93
hsa0481031	Liver	Cirrhotic	Regulation of actin cytoskeleton	100/2530	229/8465	5.28e-06	5.50e-05	3.39e-05	100
hsa051651	Liver	Cirrhotic	Human papillomavirus infection	124/2530	331/8465	1.55e-03	7.83e-03	4.83e-03	124
hsa0451041	Liver	HCC	Focal adhesion	125/4020	203/8465	3.12e-05	1.88e-04	1.04e-04	125
hsa051652	Liver	HCC	Human papillomavirus infection	188/4020	331/8465	3.34e-04	1.49e-03	8.29e-04	188

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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
COL1A1	ITGA1_ITGB1	COL1A1_ITGA1_ITGB1	COLLAGEN	Breast	ADJ
COL1A2	ITGA1_ITGB1	COL1A2_ITGA1_ITGB1	COLLAGEN	Breast	ADJ
COL4A1	ITGA1_ITGB1	COL4A1_ITGA1_ITGB1	COLLAGEN	Breast	ADJ
COL4A2	ITGA1_ITGB1	COL4A2_ITGA1_ITGB1	COLLAGEN	Breast	ADJ
COL6A1	ITGA1_ITGB1	COL6A1_ITGA1_ITGB1	COLLAGEN	Breast	ADJ
COL6A2	ITGA1_ITGB1	COL6A2_ITGA1_ITGB1	COLLAGEN	Breast	ADJ
COL6A3	ITGA1_ITGB1	COL6A3_ITGA1_ITGB1	COLLAGEN	Breast	ADJ
LAMA2	ITGA1_ITGB1	LAMA2_ITGA1_ITGB1	LAMININ	Breast	ADJ
LAMA4	ITGA1_ITGB1	LAMA4_ITGA1_ITGB1	LAMININ	Breast	ADJ
LAMB2	ITGA1_ITGB1	LAMB2_ITGA1_ITGB1	LAMININ	Breast	ADJ
LAMB3	ITGA1_ITGB1	LAMB3_ITGA1_ITGB1	LAMININ	Breast	ADJ
LAMC1	ITGA1_ITGB1	LAMC1_ITGA1_ITGB1	LAMININ	Breast	ADJ
LAMC2	ITGA1_ITGB1	LAMC2_ITGA1_ITGB1	LAMININ	Breast	ADJ
COL1A1	ITGA1_ITGB1	COL1A1_ITGA1_ITGB1	COLLAGEN	Breast	DCIS
COL1A2	ITGA1_ITGB1	COL1A2_ITGA1_ITGB1	COLLAGEN	Breast	DCIS
COL4A1	ITGA1_ITGB1	COL4A1_ITGA1_ITGB1	COLLAGEN	Breast	DCIS
COL4A2	ITGA1_ITGB1	COL4A2_ITGA1_ITGB1	COLLAGEN	Breast	DCIS
COL6A1	ITGA1_ITGB1	COL6A1_ITGA1_ITGB1	COLLAGEN	Breast	DCIS
COL6A2	ITGA1_ITGB1	COL6A2_ITGA1_ITGB1	COLLAGEN	Breast	DCIS
COL6A3	ITGA1_ITGB1	COL6A3_ITGA1_ITGB1	COLLAGEN	Breast	DCIS

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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

ITGA1

SNV

Missense_Mutation

c.2075N>A

p.Gly692Glu

p.G692E

P56199

protein_coding

tolerated(0.29)

possibly_damaging(0.828)

TCGA-A2-A0CX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

ITGA1

SNV

Missense_Mutation

c.1924N>C

p.Asp642His

p.D642H

P56199

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A8-A09Q-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

ITGA1

SNV

Missense_Mutation

novel

c.2846N>C

p.Gly949Ala

p.G949A

P56199

protein_coding

tolerated(0.08)

possibly_damaging(0.595)

TCGA-AC-A62X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ITGA1

SNV

Missense_Mutation

novel

c.485N>T

p.Ala162Val

p.A162V

P56199

protein_coding

deleterious(0.02)

probably_damaging(0.916)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ITGA1

SNV

Missense_Mutation

rs148483490

c.2029N>A

p.Glu677Lys

p.E677K

P56199

protein_coding

tolerated(0.64)

benign(0.026)

TCGA-AR-A1AO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

ITGA1

SNV

Missense_Mutation

rs368258489

c.1913N>G

p.His638Arg

p.H638R

P56199

protein_coding

deleterious(0.04)

benign(0.254)

TCGA-B6-A0RU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ITGA1

SNV

Missense_Mutation

c.2224N>C

p.Glu742Gln

p.E742Q

P56199

protein_coding

deleterious(0.01)

probably_damaging(0.949)

TCGA-BH-A0HK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

ITGA1

SNV

Missense_Mutation

c.2255N>A

p.Arg752Gln

p.R752Q

P56199

protein_coding

tolerated(0.22)

benign(0.017)

TCGA-E2-A150-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

ITGA1

SNV

Missense_Mutation

c.3299G>C

p.Ser1100Thr

p.S1100T

P56199

protein_coding

tolerated(0.65)

benign(0.003)

TCGA-E9-A1R2-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxotere

ITGA1

SNV

Missense_Mutation

c.596G>C

p.Arg199Thr

p.R199T

P56199

protein_coding

tolerated(0.19)

benign(0.007)

TCGA-PL-A8LV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

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
3672	ITGA1	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE		SAN-300	SAN-300
3672	ITGA1	DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, CELL SURFACE		SAN-300	SAN-300

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