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: BCAR1

Gene summary for BCAR1

Gene summary.

Gene information	Species	Human
	Gene symbol	BCAR1
	Gene ID	9564
	Gene name	BCAR1 scaffold protein, Cas family member
	Gene Alias	CAS
	Cytomap	16q23.1
	Gene Type	protein-coding
	GO ID	GO:0001558
	UniProtAcc	P56945

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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
9564	BCAR1	LZE4T	Human	Esophagus	ESCC	1.10e-02	-1.51e-01	0.0811
9564	BCAR1	LZE8T	Human	Esophagus	ESCC	1.01e-03	-1.79e-02	0.067
9564	BCAR1	LZE20T	Human	Esophagus	ESCC	1.03e-02	4.13e-02	0.0662
9564	BCAR1	LZE24T	Human	Esophagus	ESCC	1.83e-06	3.78e-01	0.0596
9564	BCAR1	LZE21T	Human	Esophagus	ESCC	1.06e-02	-3.38e-02	0.0655
9564	BCAR1	P1T-E	Human	Esophagus	ESCC	1.45e-04	1.75e-01	0.0875
9564	BCAR1	P2T-E	Human	Esophagus	ESCC	9.90e-08	-1.02e-01	0.1177
9564	BCAR1	P5T-E	Human	Esophagus	ESCC	2.52e-05	3.29e-02	0.1327
9564	BCAR1	P8T-E	Human	Esophagus	ESCC	2.33e-15	1.12e-01	0.0889
9564	BCAR1	P9T-E	Human	Esophagus	ESCC	2.35e-12	-1.26e-02	0.1131
9564	BCAR1	P11T-E	Human	Esophagus	ESCC	3.51e-06	5.57e-01	0.1426
9564	BCAR1	P12T-E	Human	Esophagus	ESCC	7.64e-13	2.56e-01	0.1122
9564	BCAR1	P15T-E	Human	Esophagus	ESCC	7.87e-07	7.52e-02	0.1149
9564	BCAR1	P16T-E	Human	Esophagus	ESCC	2.83e-06	-1.67e-01	0.1153
9564	BCAR1	P17T-E	Human	Esophagus	ESCC	8.24e-03	2.16e-01	0.1278
9564	BCAR1	P19T-E	Human	Esophagus	ESCC	8.14e-05	3.05e-01	0.1662
9564	BCAR1	P20T-E	Human	Esophagus	ESCC	1.37e-06	2.73e-01	0.1124
9564	BCAR1	P21T-E	Human	Esophagus	ESCC	5.02e-13	2.84e-01	0.1617
9564	BCAR1	P22T-E	Human	Esophagus	ESCC	1.01e-12	-6.27e-02	0.1236
9564	BCAR1	P23T-E	Human	Esophagus	ESCC	5.53e-21	3.36e-01	0.108

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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
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:000701512	Liver	Cirrhotic	actin filament organization	171/4634	442/18723	3.93e-11	2.30e-09	171
GO:004343412	Liver	Cirrhotic	response to peptide hormone	149/4634	414/18723	1.70e-07	4.49e-06	149
GO:007137511	Liver	Cirrhotic	cellular response to peptide hormone stimulus	110/4634	290/18723	3.73e-07	8.82e-06	110
GO:190165311	Liver	Cirrhotic	cellular response to peptide	129/4634	359/18723	1.23e-06	2.49e-05	129
GO:003286911	Liver	Cirrhotic	cellular response to insulin stimulus	80/4634	203/18723	2.55e-06	4.63e-05	80
GO:001604911	Liver	Cirrhotic	cell growth	160/4634	482/18723	1.50e-05	2.07e-04	160
GO:000722911	Liver	Cirrhotic	integrin-mediated signaling pathway	46/4634	107/18723	2.66e-05	3.42e-04	46
GO:003286811	Liver	Cirrhotic	response to insulin	95/4634	264/18723	2.77e-05	3.54e-04	95
GO:000155811	Liver	Cirrhotic	regulation of cell growth	132/4634	414/18723	5.53e-04	4.36e-03	132
GO:00315326	Liver	Cirrhotic	actin cytoskeleton reorganization	42/4634	107/18723	6.28e-04	4.81e-03	42
GO:003812711	Liver	Cirrhotic	ERBB signaling pathway	46/4634	121/18723	8.08e-04	5.93e-03	46
GO:000828611	Liver	Cirrhotic	insulin receptor signaling pathway	44/4634	116/18723	1.09e-03	7.59e-03	44
GO:000166712	Liver	Cirrhotic	ameboidal-type cell migration	145/4634	475/18723	2.23e-03	1.36e-02	145
GO:00106327	Liver	Cirrhotic	regulation of epithelial cell migration	93/4634	292/18723	3.46e-03	1.92e-02	93
GO:00106317	Liver	Cirrhotic	epithelial cell migration	110/4634	357/18723	5.14e-03	2.65e-02	110
GO:000717311	Liver	Cirrhotic	epidermal growth factor receptor signaling pathway	39/4634	108/18723	5.49e-03	2.79e-02	39
GO:00901327	Liver	Cirrhotic	epithelium migration	110/4634	360/18723	6.79e-03	3.35e-02	110
GO:00901307	Liver	Cirrhotic	tissue migration	111/4634	365/18723	7.66e-03	3.61e-02	111
GO:00106346	Liver	Cirrhotic	positive regulation of epithelial cell migration	58/4634	176/18723	8.54e-03	3.96e-02	58
GO:003286821	Liver	HCC	response to insulin	172/7958	264/18723	7.14e-14	4.23e-12	172

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05131211	Esophagus	ESCC	Shigellosis	176/4205	247/8465	2.27e-12	4.01e-11	2.05e-11	176
hsa0513526	Esophagus	ESCC	Yersinia infection	100/4205	137/8465	1.80e-08	1.59e-07	8.12e-08	100
hsa05163210	Esophagus	ESCC	Human cytomegalovirus infection	148/4205	225/8465	5.73e-07	4.00e-06	2.05e-06	148
hsa05100211	Esophagus	ESCC	Bacterial invasion of epithelial cells	59/4205	77/8465	1.05e-06	6.76e-06	3.46e-06	59
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
hsa05131310	Esophagus	ESCC	Shigellosis	176/4205	247/8465	2.27e-12	4.01e-11	2.05e-11	176
hsa05135111	Esophagus	ESCC	Yersinia infection	100/4205	137/8465	1.80e-08	1.59e-07	8.12e-08	100
hsa0516338	Esophagus	ESCC	Human cytomegalovirus infection	148/4205	225/8465	5.73e-07	4.00e-06	2.05e-06	148
hsa05100310	Esophagus	ESCC	Bacterial invasion of epithelial cells	59/4205	77/8465	1.05e-06	6.76e-06	3.46e-06	59
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
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
hsa0513122	Liver	Cirrhotic	Shigellosis	105/2530	247/8465	1.31e-05	1.21e-04	7.48e-05	105
hsa0510014	Liver	Cirrhotic	Bacterial invasion of epithelial cells	40/2530	77/8465	3.92e-05	2.84e-04	1.75e-04	40
hsa0467022	Liver	Cirrhotic	Leukocyte transendothelial migration	49/2530	114/8465	1.92e-03	8.55e-03	5.27e-03	49
hsa0513522	Liver	Cirrhotic	Yersinia infection	57/2530	137/8465	2.16e-03	9.41e-03	5.80e-03	57
hsa0516312	Liver	Cirrhotic	Human cytomegalovirus infection	87/2530	225/8465	2.67e-03	1.10e-02	6.76e-03	87
hsa0451031	Liver	Cirrhotic	Focal adhesion	93/2530	203/8465	9.27e-07	1.10e-05	6.80e-06	93

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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

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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

BCAR1

SNV

Missense_Mutation

novel

c.2377N>C

p.Tyr793His

p.Y793H

P56945

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A2-A3Y0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

BCAR1

SNV

Missense_Mutation

c.998N>G

p.Tyr333Cys

p.Y333C

P56945

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

BCAR1

SNV

Missense_Mutation

rs773405077

c.848C>T

p.Pro283Leu

p.P283L

P56945

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

BCAR1

SNV

Missense_Mutation

c.2200N>G

p.Ile734Val

p.I734V

P56945

protein_coding

deleterious(0)

possibly_damaging(0.881)

TCGA-E9-A1RF-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

BCAR1

insertion

Nonsense_Mutation

novel

c.1280_1281insCTCACAGCTGCCATAGGCTCAG

p.Gly428SerfsTer5

p.G428Sfs*5

P56945

protein_coding

TCGA-A2-A0CU-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

BCAR1

insertion

Frame_Shift_Ins

novel

c.2395_2396insGGCTTGGAGAAGACCCTTGCCCTGGGCAAGTGTGTCC

p.Ala799GlyfsTer67

p.A799Gfs*67

P56945

protein_coding

TCGA-BH-A0B1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

adriamycin

BCAR1

SNV

Missense_Mutation

rs763926002

c.620C>T

p.Ala207Val

p.A207V

P56945

protein_coding

tolerated(0.15)

benign(0.097)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

BCAR1

SNV

Missense_Mutation

c.1028N>G

p.Leu343Arg

p.L343R

P56945

protein_coding

tolerated(0.09)

probably_damaging(0.991)

TCGA-A6-5665-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

BCAR1

SNV

Missense_Mutation

c.314N>A

p.Arg105His

p.R105H

P56945

protein_coding

deleterious(0)

probably_damaging(0.989)

TCGA-A6-5665-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

BCAR1

SNV

Missense_Mutation

novel

c.2433N>A

p.Phe811Leu

p.F811L

P56945

protein_coding

tolerated(0.24)

probably_damaging(0.972)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

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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
9564	BCAR1	KINASE		celecoxib	CELECOXIB	22336956

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