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: BTN3A2

Gene summary for BTN3A2

Gene summary.

Gene information	Species	Human
	Gene symbol	BTN3A2
	Gene ID	11118
	Gene name	butyrophilin subfamily 3 member A2
	Gene Alias	BT3.2
	Cytomap	6p22.2
	Gene Type	protein-coding
	GO ID	GO:0001816
	UniProtAcc	P78410

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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
11118	BTN3A2	HTA11_3410_2000001011	Human	Colorectum	AD	8.54e-08	2.71e-01	0.0155
11118	BTN3A2	HTA11_1938_2000001011	Human	Colorectum	AD	1.82e-11	5.26e-01	-0.0811
11118	BTN3A2	HTA11_78_2000001011	Human	Colorectum	AD	2.51e-03	3.05e-01	-0.1088
11118	BTN3A2	HTA11_347_2000001011	Human	Colorectum	AD	5.48e-05	2.26e-01	-0.1954
11118	BTN3A2	HTA11_3361_2000001011	Human	Colorectum	AD	1.97e-02	1.82e-01	-0.1207
11118	BTN3A2	HTA11_696_2000001011	Human	Colorectum	AD	2.46e-04	2.99e-01	-0.1464
11118	BTN3A2	HTA11_1391_2000001011	Human	Colorectum	AD	3.65e-11	4.52e-01	-0.059
11118	BTN3A2	HTA11_546_2000001011	Human	Colorectum	AD	1.53e-03	3.09e-01	-0.0842
11118	BTN3A2	HTA11_866_3004761011	Human	Colorectum	AD	1.21e-08	3.28e-01	0.096
11118	BTN3A2	HTA11_10711_2000001011	Human	Colorectum	AD	1.84e-02	2.22e-01	0.0338
11118	BTN3A2	HTA11_7696_3000711011	Human	Colorectum	AD	6.24e-03	2.51e-01	0.0674
11118	BTN3A2	HTA11_99999970781_79442	Human	Colorectum	MSS	5.33e-05	2.71e-01	0.294
11118	BTN3A2	HTA11_99999965104_69814	Human	Colorectum	MSS	1.61e-02	2.93e-01	0.281
11118	BTN3A2	LZE4T	Human	Esophagus	ESCC	2.07e-04	1.46e-01	0.0811
11118	BTN3A2	LZE7T	Human	Esophagus	ESCC	2.02e-04	2.34e-01	0.0667
11118	BTN3A2	LZE8T	Human	Esophagus	ESCC	9.10e-10	2.70e-01	0.067
11118	BTN3A2	LZE20T	Human	Esophagus	ESCC	1.27e-06	3.52e-01	0.0662
11118	BTN3A2	LZE24T	Human	Esophagus	ESCC	7.59e-46	1.15e+00	0.0596
11118	BTN3A2	LZE21T	Human	Esophagus	ESCC	5.86e-03	2.10e-01	0.0655
11118	BTN3A2	LZE6T	Human	Esophagus	ESCC	1.18e-10	4.75e-01	0.0845

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		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
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:00508528	Esophagus	ESCC	T cell receptor signaling pathway	73/8552	123/18723	1.54e-03	7.24e-03	73
GO:000181916	Esophagus	ESCC	positive regulation of cytokine production	244/8552	467/18723	2.29e-03	1.01e-02	244
GO:00508527	Oral cavity	OSCC	T cell receptor signaling pathway	68/7305	123/18723	1.80e-04	1.22e-03	68
GO:000181910	Oral cavity	OSCC	positive regulation of cytokine production	213/7305	467/18723	1.93e-03	8.96e-03	213
GO:00027646	Oral cavity	OSCC	immune response-regulating signaling pathway	212/7305	468/18723	2.93e-03	1.27e-02	212
GO:000276413	Oral cavity	EOLP	immune response-regulating signaling pathway	108/2218	468/18723	4.04e-12	7.34e-10	108
GO:00027683	Oral cavity	EOLP	immune response-regulating cell surface receptor signaling pathway	66/2218	315/18723	2.44e-06	5.45e-05	66
GO:005085214	Oral cavity	EOLP	T cell receptor signaling pathway	33/2218	123/18723	4.19e-06	8.76e-05	33
GO:000181915	Oral cavity	EOLP	positive regulation of cytokine production	87/2218	467/18723	1.08e-05	1.92e-04	87
GO:00024292	Oral cavity	EOLP	immune response-activating cell surface receptor signaling pathway	60/2218	291/18723	1.16e-05	2.00e-04	60
GO:00027572	Oral cavity	EOLP	immune response-activating signal transduction	60/2218	291/18723	1.16e-05	2.00e-04	60
GO:00022534	Oral cavity	EOLP	activation of immune response	72/2218	375/18723	2.18e-05	3.35e-04	72
GO:00508514	Oral cavity	EOLP	antigen receptor-mediated signaling pathway	48/2218	240/18723	1.79e-04	1.84e-03	48
GO:00024433	Oral cavity	EOLP	leukocyte mediated immunity	73/2218	440/18723	1.78e-03	1.16e-02	73
GO:00024604	Oral cavity	EOLP	adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	58/2218	356/18723	7.27e-03	3.52e-02	58
GO:00024566	Oral cavity	EOLP	T cell mediated immunity	22/2218	109/18723	8.31e-03	3.91e-02	22
GO:005085221	Skin	cSCC	T cell receptor signaling pathway	44/4864	123/18723	1.02e-02	4.47e-02	44
GO:005085210	Thyroid	PTC	T cell receptor signaling pathway	52/5968	123/18723	9.58e-03	3.93e-02	52
GO:000181924	Thyroid	ATC	positive regulation of cytokine production	189/6293	467/18723	1.00e-03	5.31e-03	189

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

BTN3A2

SNV

Missense_Mutation

rs774256825

c.457N>A

p.Glu153Lys

p.E153K

P78410

protein_coding

deleterious(0.02)

benign(0.207)

TCGA-A8-A09Q-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

BTN3A2

SNV

Missense_Mutation

c.183N>C

p.Glu61Asp

p.E61D

P78410

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-B6-A0IJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

BTN3A2

SNV

Missense_Mutation

novel

c.475G>A

p.Asp159Asn

p.D159N

P78410

protein_coding

tolerated(0.28)

benign(0.001)

TCGA-BH-A0DK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

BTN3A2

SNV

Missense_Mutation

novel

c.206N>C

p.Ser69Thr

p.S69T

P78410

protein_coding

deleterious(0)

possibly_damaging(0.608)

TCGA-BH-A0H9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

BTN3A2

SNV

Missense_Mutation

c.815N>C

p.Arg272Thr

p.R272T

P78410

protein_coding

deleterious(0.03)

benign(0.156)

TCGA-C8-A27B-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

BTN3A2

SNV

Missense_Mutation

novel

c.527A>C

p.Gln176Pro

p.Q176P

P78410

protein_coding

deleterious(0.01)

possibly_damaging(0.469)

TCGA-E2-A1LB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

BTN3A2

SNV

Missense_Mutation

rs766201604

c.551G>A

p.Gly184Glu

p.G184E

P78410

protein_coding

deleterious(0.01)

probably_damaging(0.976)

TCGA-C5-A2LZ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Unknown

BTN3A2

SNV

Missense_Mutation

rs376441641

c.985G>A

p.Asp329Asn

p.D329N

P78410

protein_coding

tolerated_low_confidence(0.24)

benign(0)

TCGA-MY-A5BF-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

BTN3A2

SNV

Missense_Mutation

novel

c.781N>G

p.Leu261Val

p.L261V

P78410

protein_coding

tolerated(0.08)

benign(0.006)

TCGA-AA-3520-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

BTN3A2

SNV

Missense_Mutation

rs376441641

c.985G>A

p.Asp329Asn

p.D329N

P78410

protein_coding

tolerated_low_confidence(0.24)

benign(0)

TCGA-AA-A01R-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

5-fluorouracil

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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

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