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: TBRG4

Gene summary for TBRG4

Gene summary.

Gene information	Species	Human
	Gene symbol	TBRG4
	Gene ID	9238
	Gene name	transforming growth factor beta regulator 4
	Gene Alias	CPR2
	Cytomap	7p13
	Gene Type	protein-coding
	GO ID	GO:0000959
	UniProtAcc	B3KRS4

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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
9238	TBRG4	LZE2T	Human	Esophagus	ESCC	9.12e-03	8.06e-01	0.082
9238	TBRG4	LZE4T	Human	Esophagus	ESCC	1.28e-14	2.66e-01	0.0811
9238	TBRG4	LZE5T	Human	Esophagus	ESCC	3.78e-02	1.35e-01	0.0514
9238	TBRG4	LZE7T	Human	Esophagus	ESCC	2.32e-10	4.62e-01	0.0667
9238	TBRG4	LZE8T	Human	Esophagus	ESCC	9.41e-06	2.09e-01	0.067
9238	TBRG4	LZE20T	Human	Esophagus	ESCC	2.12e-04	1.21e-01	0.0662
9238	TBRG4	LZE24T	Human	Esophagus	ESCC	1.33e-09	2.61e-01	0.0596
9238	TBRG4	LZE21T	Human	Esophagus	ESCC	6.14e-06	3.21e-01	0.0655
9238	TBRG4	LZE6T	Human	Esophagus	ESCC	9.20e-05	2.38e-01	0.0845
9238	TBRG4	P1T-E	Human	Esophagus	ESCC	9.13e-06	4.38e-01	0.0875
9238	TBRG4	P2T-E	Human	Esophagus	ESCC	2.21e-31	5.04e-01	0.1177
9238	TBRG4	P4T-E	Human	Esophagus	ESCC	5.41e-23	6.36e-01	0.1323
9238	TBRG4	P5T-E	Human	Esophagus	ESCC	1.47e-09	1.62e-01	0.1327
9238	TBRG4	P8T-E	Human	Esophagus	ESCC	2.73e-22	3.68e-01	0.0889
9238	TBRG4	P9T-E	Human	Esophagus	ESCC	1.70e-20	4.34e-01	0.1131
9238	TBRG4	P10T-E	Human	Esophagus	ESCC	8.22e-27	3.76e-01	0.116
9238	TBRG4	P11T-E	Human	Esophagus	ESCC	1.41e-18	7.49e-01	0.1426
9238	TBRG4	P12T-E	Human	Esophagus	ESCC	2.70e-24	4.54e-01	0.1122
9238	TBRG4	P15T-E	Human	Esophagus	ESCC	2.21e-26	5.91e-01	0.1149
9238	TBRG4	P16T-E	Human	Esophagus	ESCC	7.01e-35	6.33e-01	0.1153

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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:1903311110	Esophagus	ESCC	regulation of mRNA metabolic process	210/8552	288/18723	3.25e-21	5.56e-19	210
GO:0006401110	Esophagus	ESCC	RNA catabolic process	204/8552	278/18723	3.39e-21	5.66e-19	204
GO:014005313	Esophagus	ESCC	mitochondrial gene expression	93/8552	108/18723	1.96e-18	2.03e-16	93
GO:0034655110	Esophagus	ESCC	nucleobase-containing compound catabolic process	272/8552	407/18723	2.92e-18	2.90e-16	272
GO:0006402110	Esophagus	ESCC	mRNA catabolic process	170/8552	232/18723	8.70e-18	8.00e-16	170
GO:004670018	Esophagus	ESCC	heterocycle catabolic process	286/8552	445/18723	1.12e-15	7.47e-14	286
GO:004427019	Esophagus	ESCC	cellular nitrogen compound catabolic process	288/8552	451/18723	3.03e-15	1.79e-13	288
GO:001943918	Esophagus	ESCC	aromatic compound catabolic process	295/8552	467/18723	1.09e-14	5.98e-13	295
GO:190136118	Esophagus	ESCC	organic cyclic compound catabolic process	307/8552	495/18723	9.99e-14	4.80e-12	307
GO:006101319	Esophagus	ESCC	regulation of mRNA catabolic process	115/8552	166/18723	5.90e-10	1.49e-08	115
GO:004348719	Esophagus	ESCC	regulation of RNA stability	117/8552	170/18723	7.91e-10	1.94e-08	117
GO:004348819	Esophagus	ESCC	regulation of mRNA stability	109/8552	158/18723	2.40e-09	5.35e-08	109
GO:00009592	Esophagus	ESCC	mitochondrial RNA metabolic process	39/8552	49/18723	1.20e-06	1.49e-05	39
GO:00009631	Esophagus	ESCC	mitochondrial RNA processing	19/8552	20/18723	3.83e-06	4.14e-05	19
GO:190136111	Liver	Cirrhotic	organic cyclic compound catabolic process	213/4634	495/18723	1.58e-19	3.67e-17	213
GO:001943911	Liver	Cirrhotic	aromatic compound catabolic process	202/4634	467/18723	6.93e-19	1.28e-16	202
GO:190331111	Liver	Cirrhotic	regulation of mRNA metabolic process	140/4634	288/18723	1.07e-18	1.91e-16	140
GO:004427011	Liver	Cirrhotic	cellular nitrogen compound catabolic process	195/4634	451/18723	2.99e-18	4.94e-16	195
GO:004670011	Liver	Cirrhotic	heterocycle catabolic process	192/4634	445/18723	7.17e-18	1.12e-15	192
GO:003465511	Liver	Cirrhotic	nucleobase-containing compound catabolic process	171/4634	407/18723	9.07e-15	9.33e-13	171

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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

TBRG4

SNV

Missense_Mutation

novel

c.1607N>A

p.Pro536His

p.P536H

Q969Z0

protein_coding

deleterious(0.01)

probably_damaging(0.915)

TCGA-AR-A2LN-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

letrozole

TBRG4

SNV

Missense_Mutation

novel

c.533N>G

p.Lys178Arg

p.K178R

Q969Z0

protein_coding

tolerated(1)

benign(0.001)

TCGA-BH-A42T-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TBRG4

SNV

Missense_Mutation

rs143689271

c.811C>T

p.Arg271Trp

p.R271W

Q969Z0

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-D8-A1J8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

nolvadex

TBRG4

insertion

In_Frame_Ins

novel

c.68_69insCAC

p.Met23delinsIleThr

p.M23delinsIT

Q969Z0

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

TBRG4

insertion

Frame_Shift_Ins

novel

c.67_68insGAATTCA

p.Met23ArgfsTer17

p.M23Rfs*17

Q969Z0

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

TBRG4

insertion

In_Frame_Ins

novel

c.1570_1571insGTC

p.Ala524delinsGlyPro

p.A524delinsGP

Q969Z0

protein_coding

TCGA-B6-A0IN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TBRG4

insertion

Nonsense_Mutation

novel

c.1568_1569insGGCTTCCTGATAGTGGACGTGAGTACCTCTTGGGCAGG

p.Asp523GlufsTer4

p.D523Efs*4

Q969Z0

protein_coding

TCGA-B6-A0IN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TBRG4

deletion

In_Frame_Del

c.606_659delGCTGCTGGCTGAGCTGCTCACACACCTGGAAAGGCGTTGGACAGAAATTGAAGA

p.Glu202_Glu219del

p.E202_E219del

Q969Z0

protein_coding

TCGA-E2-A1LH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

TBRG4

SNV

Missense_Mutation

novel

c.337G>C

p.Glu113Gln

p.E113Q

Q969Z0

protein_coding

tolerated(0.16)

benign(0.08)

TCGA-HM-A4S6-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

TBRG4

SNV

Missense_Mutation

c.776N>A

p.Arg259Gln

p.R259Q

Q969Z0

protein_coding

tolerated(0.05)

probably_damaging(0.974)

TCGA-A6-3809-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

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

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