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: BTN3A1

Gene summary for BTN3A1

Gene summary.

Gene information	Species	Human
	Gene symbol	BTN3A1
	Gene ID	11119
	Gene name	butyrophilin subfamily 3 member A1
	Gene Alias	BT3.1
	Cytomap	6p22.2
	Gene Type	protein-coding
	GO ID	GO:0001775
	UniProtAcc	O00481

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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
11119	BTN3A1	Dong_P1	Human	Prostate	Tumor	1.55e-06	9.57e-02	0.035
11119	BTN3A1	Dong_P3	Human	Prostate	Tumor	1.24e-04	6.93e-02	0.0278
11119	BTN3A1	GSM5353217_PA_PB1A_Pool_2_S107_L004	Human	Prostate	Tumor	3.28e-02	6.78e-01	0.156
11119	BTN3A1	GSM5353221_PA_PB2A_Pool_1_3_S25_L001	Human	Prostate	Tumor	4.43e-17	6.22e-01	0.1633
11119	BTN3A1	GSM5353222_PA_PB2B_Pool_1_3_S52_L002	Human	Prostate	Tumor	1.09e-05	3.29e-01	0.1608
11119	BTN3A1	GSM5353223_PA_PB2B_Pool_2_S26_L001	Human	Prostate	Tumor	3.18e-08	4.71e-01	0.1604
11119	BTN3A1	GSM5353224_PA_PR5186_Pool_1_2_3_S27_L001	Human	Prostate	Tumor	4.94e-04	2.77e-01	0.1621
11119	BTN3A1	GSM5353225_PA_PR5196-1_Pool_1_2_3_S53_L002	Human	Prostate	Tumor	1.24e-07	6.87e-01	0.1619
11119	BTN3A1	GSM5353226_PA_PR5196-2_Pool_1_2_3_S54_L002	Human	Prostate	Tumor	6.68e-04	5.46e-01	0.159
11119	BTN3A1	GSM5353227_PA_PR5199-193K_Pool_1_2_3_S55_L002	Human	Prostate	Tumor	1.18e-02	3.15e-01	0.1602
11119	BTN3A1	GSM5353240_PA_PR5254_T1_S15_L001	Human	Prostate	Tumor	8.64e-04	3.06e-01	0.1575
11119	BTN3A1	GSM5353243_PA_PR5261_T1_S23_L002	Human	Prostate	Tumor	2.45e-02	2.84e-01	0.1545

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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
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:004211018	Esophagus	ESCC	T cell activation	256/8552	487/18723	1.18e-03	5.87e-03	256
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:004211016	Oral cavity	OSCC	T cell activation	245/7305	487/18723	2.00e-07	3.22e-06	245
GO:00508527	Oral cavity	OSCC	T cell receptor signaling pathway	68/7305	123/18723	1.80e-04	1.22e-03	68
GO:004209816	Oral cavity	OSCC	T cell proliferation	100/7305	199/18723	7.93e-04	4.27e-03	100
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:00706618	Oral cavity	OSCC	leukocyte proliferation	145/7305	318/18723	9.31e-03	3.33e-02	145
GO:00466517	Oral cavity	OSCC	lymphocyte proliferation	131/7305	288/18723	1.41e-02	4.67e-02	131
GO:004211017	Oral cavity	LP	T cell activation	146/4623	487/18723	4.13e-03	2.66e-02	146
GO:000276413	Oral cavity	EOLP	immune response-regulating signaling pathway	108/2218	468/18723	4.04e-12	7.34e-10	108
GO:004211023	Oral cavity	EOLP	T cell activation	111/2218	487/18723	4.67e-12	8.17e-10	111
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:007066112	Oral cavity	EOLP	leukocyte proliferation	65/2218	318/18723	6.86e-06	1.33e-04	65
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

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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

BTN3A1

SNV

Missense_Mutation

c.944N>T

p.Arg315Ile

p.R315I

O00481

protein_coding

deleterious(0.02)

benign(0.003)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

BTN3A1

SNV

Missense_Mutation

novel

c.100N>T

p.Leu34Phe

p.L34F

O00481

protein_coding

tolerated(0.06)

possibly_damaging(0.812)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

BTN3A1

SNV

Missense_Mutation

c.139G>C

p.Asp47His

p.D47H

O00481

protein_coding

deleterious(0.01)

probably_damaging(0.979)

TCGA-BH-A0AW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

BTN3A1

SNV

Missense_Mutation

c.206N>C

p.Ser69Thr

p.S69T

O00481

protein_coding

deleterious(0)

possibly_damaging(0.527)

TCGA-BH-A0H9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

BTN3A1

SNV

Missense_Mutation

c.802N>G

p.Tyr268Asp

p.Y268D

O00481

protein_coding

tolerated(0.07)

benign(0.272)

TCGA-E2-A15S-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

BTN3A1

insertion

Frame_Shift_Ins

novel

c.381_382insAATAATTA

p.Phe128AsnfsTer17

p.F128Nfs*17

O00481

protein_coding

TCGA-B6-A0IB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

BTN3A1

deletion

Frame_Shift_Del

rs35139329

c.833delA

p.Lys278ArgfsTer13

p.K278Rfs*13

O00481

protein_coding

TCGA-BH-A0HA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

BTN3A1

deletion

Frame_Shift_Del

novel

c.1375delN

p.Val460TrpfsTer42

p.V460Wfs*42

O00481

protein_coding

TCGA-PL-A8LY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

BTN3A1

SNV

Missense_Mutation

rs754276670

c.682G>A

p.Gly228Ser

p.G228S

O00481

protein_coding

tolerated(0.33)

benign(0.02)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

BTN3A1

SNV

Missense_Mutation

c.974G>C

p.Arg325Thr

p.R325T

O00481

protein_coding

deleterious(0.02)

benign(0.026)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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
11119	BTN3A1	EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME, B30_2 SPRY DOMAIN		340590246

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