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: BCAT2

Gene summary for BCAT2

Gene summary.

Gene information	Species	Human
	Gene symbol	BCAT2
	Gene ID	587
	Gene name	branched chain amino acid transaminase 2
	Gene Alias	BCAM
	Cytomap	19q13.33
	Gene Type	protein-coding
	GO ID	GO:0006082
	UniProtAcc	O15382

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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
587	BCAT2	HTA11_347_2000001011	Human	Colorectum	AD	3.68e-10	4.20e-01	-0.1954
587	BCAT2	HTA11_696_2000001011	Human	Colorectum	AD	1.61e-03	2.72e-01	-0.1464
587	BCAT2	HTA11_866_3004761011	Human	Colorectum	AD	5.86e-05	3.18e-01	0.096
587	BCAT2	HTA11_99999965104_69814	Human	Colorectum	MSS	7.59e-06	3.90e-01	0.281
587	BCAT2	A015-C-203	Human	Colorectum	FAP	1.16e-02	-9.40e-02	-0.1294
587	BCAT2	A015-C-106	Human	Colorectum	FAP	1.45e-03	-1.31e-01	-0.0511
587	BCAT2	A015-C-104	Human	Colorectum	FAP	1.55e-02	-4.04e-02	-0.1899
587	BCAT2	A002-C-016	Human	Colorectum	FAP	1.03e-02	-1.11e-01	0.0521
587	BCAT2	A002-C-116	Human	Colorectum	FAP	6.34e-03	-1.18e-01	-0.0452
587	BCAT2	LZE4T	Human	Esophagus	ESCC	1.26e-14	3.63e-01	0.0811
587	BCAT2	LZE5T	Human	Esophagus	ESCC	8.45e-06	5.49e-01	0.0514
587	BCAT2	LZE7T	Human	Esophagus	ESCC	8.95e-06	4.89e-01	0.0667
587	BCAT2	LZE8T	Human	Esophagus	ESCC	1.21e-06	2.64e-01	0.067
587	BCAT2	LZE20T	Human	Esophagus	ESCC	2.68e-02	9.46e-02	0.0662
587	BCAT2	LZE22D1	Human	Esophagus	HGIN	4.45e-04	1.89e-01	0.0595
587	BCAT2	LZE22T	Human	Esophagus	ESCC	1.18e-09	6.55e-01	0.068
587	BCAT2	LZE24T	Human	Esophagus	ESCC	6.84e-16	3.98e-01	0.0596
587	BCAT2	LZE6T	Human	Esophagus	ESCC	9.39e-03	2.66e-01	0.0845
587	BCAT2	P1T-E	Human	Esophagus	ESCC	2.39e-13	4.68e-01	0.0875
587	BCAT2	P2T-E	Human	Esophagus	ESCC	3.14e-20	3.66e-01	0.1177

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
Colorectum (GSE201348)		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
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

∗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:0044282	Colorectum	AD	small molecule catabolic process	118/3918	376/18723	1.05e-06	3.55e-05	118
GO:0009083	Colorectum	AD	branched-chain amino acid catabolic process	10/3918	15/18723	1.68e-04	2.29e-03	10
GO:0016054	Colorectum	AD	organic acid catabolic process	73/3918	240/18723	3.20e-04	3.81e-03	73
GO:0046395	Colorectum	AD	carboxylic acid catabolic process	70/3918	236/18723	9.06e-04	8.71e-03	70
GO:0006520	Colorectum	AD	cellular amino acid metabolic process	81/3918	284/18723	1.37e-03	1.19e-02	81
GO:0009081	Colorectum	AD	branched-chain amino acid metabolic process	10/3918	19/18723	2.25e-03	1.77e-02	10
GO:00090831	Colorectum	MSS	branched-chain amino acid catabolic process	10/3467	15/18723	5.64e-05	9.87e-04	10
GO:00090811	Colorectum	MSS	branched-chain amino acid metabolic process	10/3467	19/18723	8.39e-04	8.68e-03	10
GO:00442822	Colorectum	MSS	small molecule catabolic process	94/3467	376/18723	9.85e-04	9.86e-03	94
GO:00160542	Colorectum	MSS	organic acid catabolic process	61/3467	240/18723	4.72e-03	3.31e-02	61
GO:0046394	Colorectum	MSS	carboxylic acid biosynthetic process	76/3467	314/18723	6.71e-03	4.38e-02	76
GO:0016053	Colorectum	MSS	organic acid biosynthetic process	76/3467	316/18723	7.88e-03	4.84e-02	76
GO:00442823	Colorectum	FAP	small molecule catabolic process	77/2622	376/18723	3.25e-04	4.16e-03	77
GO:00160543	Colorectum	FAP	organic acid catabolic process	50/2622	240/18723	2.30e-03	1.85e-02	50
GO:00090832	Colorectum	FAP	branched-chain amino acid catabolic process	7/2622	15/18723	2.40e-03	1.90e-02	7
GO:00463951	Colorectum	FAP	carboxylic acid catabolic process	48/2622	236/18723	4.53e-03	3.08e-02	48
GO:1990823	Colorectum	FAP	response to leukemia inhibitory factor	23/2622	95/18723	5.32e-03	3.49e-02	23
GO:19908308	Esophagus	HGIN	cellular response to leukemia inhibitory factor	23/2587	94/18723	3.92e-03	3.54e-02	23
GO:19908238	Esophagus	HGIN	response to leukemia inhibitory factor	23/2587	95/18723	4.51e-03	3.93e-02	23
GO:00086525	Esophagus	ESCC	cellular amino acid biosynthetic process	51/8552	76/18723	1.30e-04	8.88e-04	51

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa00280	Colorectum	AD	Valine, leucine and isoleucine degradation	25/2092	48/8465	3.97e-05	3.41e-04	2.18e-04	25
hsa01230	Colorectum	AD	Biosynthesis of amino acids	28/2092	75/8465	9.99e-03	3.89e-02	2.48e-02	28
hsa002801	Colorectum	AD	Valine, leucine and isoleucine degradation	25/2092	48/8465	3.97e-05	3.41e-04	2.18e-04	25
hsa012301	Colorectum	AD	Biosynthesis of amino acids	28/2092	75/8465	9.99e-03	3.89e-02	2.48e-02	28
hsa002802	Colorectum	MSS	Valine, leucine and isoleucine degradation	21/1875	48/8465	6.73e-04	4.51e-03	2.76e-03	21
hsa002803	Colorectum	MSS	Valine, leucine and isoleucine degradation	21/1875	48/8465	6.73e-04	4.51e-03	2.76e-03	21
hsa002804	Colorectum	FAP	Valine, leucine and isoleucine degradation	18/1404	48/8465	3.94e-04	3.06e-03	1.86e-03	18
hsa002805	Colorectum	FAP	Valine, leucine and isoleucine degradation	18/1404	48/8465	3.94e-04	3.06e-03	1.86e-03	18
hsa012306	Esophagus	HGIN	Biosynthesis of amino acids	21/1383	75/8465	7.38e-03	4.63e-02	3.68e-02	21
hsa0123013	Esophagus	HGIN	Biosynthesis of amino acids	21/1383	75/8465	7.38e-03	4.63e-02	3.68e-02	21
hsa012405	Esophagus	ESCC	Biosynthesis of cofactors	97/4205	153/8465	3.88e-04	1.35e-03	6.94e-04	97
hsa002809	Esophagus	ESCC	Valine, leucine and isoleucine degradation	34/4205	48/8465	2.34e-03	6.54e-03	3.35e-03	34
hsa0123023	Esophagus	ESCC	Biosynthesis of amino acids	49/4205	75/8465	4.35e-03	1.12e-02	5.74e-03	49
hsa0124012	Esophagus	ESCC	Biosynthesis of cofactors	97/4205	153/8465	3.88e-04	1.35e-03	6.94e-04	97
hsa0028014	Esophagus	ESCC	Valine, leucine and isoleucine degradation	34/4205	48/8465	2.34e-03	6.54e-03	3.35e-03	34
hsa0123033	Esophagus	ESCC	Biosynthesis of amino acids	49/4205	75/8465	4.35e-03	1.12e-02	5.74e-03	49
hsa012404	Oral cavity	OSCC	Biosynthesis of cofactors	88/3704	153/8465	3.84e-04	1.20e-03	6.12e-04	88
hsa012305	Oral cavity	OSCC	Biosynthesis of amino acids	45/3704	75/8465	3.27e-03	8.23e-03	4.19e-03	45
hsa002808	Oral cavity	OSCC	Valine, leucine and isoleucine degradation	30/3704	48/8465	6.75e-03	1.57e-02	7.99e-03	30
hsa0124011	Oral cavity	OSCC	Biosynthesis of cofactors	88/3704	153/8465	3.84e-04	1.20e-03	6.12e-04	88

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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

BCAT2

SNV

Missense_Mutation

c.616N>A

p.Val206Met

p.V206M

O15382

protein_coding

tolerated(0.09)

benign(0.005)

TCGA-A2-A0CW-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

BCAT2

SNV

Missense_Mutation

rs11548194

c.656N>A

p.Arg219Gln

p.R219Q

O15382

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A7-A0DA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

BCAT2

SNV

Missense_Mutation

novel

c.1099N>C

p.Glu367Gln

p.E367Q

O15382

protein_coding

tolerated(0.5)

benign(0.001)

TCGA-D8-A73U-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

BCAT2

deletion

Frame_Shift_Del

novel

c.393delN

p.Met132CysfsTer75

p.M132Cfs*75

O15382

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

BCAT2

SNV

Missense_Mutation

novel

c.829G>A

p.Glu277Lys

p.E277K

O15382

protein_coding

tolerated(0.08)

benign(0.05)

TCGA-C5-A3HF-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

BCAT2

SNV

Missense_Mutation

c.1149C>G

p.Ile383Met

p.I383M

O15382

protein_coding

tolerated(0.08)

benign(0.001)

TCGA-EK-A2H1-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cetuximab

BCAT2

SNV

Missense_Mutation

c.457N>A

p.Glu153Lys

p.E153K

O15382

protein_coding

tolerated(0.59)

benign(0.023)

TCGA-VS-A9V3-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

BCAT2

SNV

Missense_Mutation

rs549092161

c.446N>A

p.Arg149His

p.R149H

O15382

protein_coding

tolerated(0.06)

probably_damaging(0.934)

TCGA-AA-A01R-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

5-fluorouracil

BCAT2

SNV

Missense_Mutation

c.7N>A

p.Ala3Thr

p.A3T

O15382

protein_coding

tolerated_low_confidence(0.14)

benign(0.001)

TCGA-AZ-6598-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

BCAT2

SNV

Missense_Mutation

novel

c.481N>A

p.Asp161Asn

p.D161N

O15382

protein_coding

tolerated(0.53)

benign(0.003)

TCGA-EI-6917-01

Colorectum

rectum adenocarcinoma

Male

<65

III/IV

Chemotherapy

5fluorouracil+oxaciplatina+l-folinian

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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
587	BCAT2	ENZYME, TRANSPORTER	inhibitor	315661169
587	BCAT2	ENZYME, TRANSPORTER	inhibitor	315661170

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