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: TBRG1

Gene summary for TBRG1

Gene summary.

Gene information	Species	Human
	Gene symbol	TBRG1
	Gene ID	84897
	Gene name	transforming growth factor beta regulator 1
	Gene Alias	NIAM
	Cytomap	11q24.2
	Gene Type	protein-coding
	GO ID	GO:0006260
	UniProtAcc	Q3YBR2

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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
84897	TBRG1	LZE4T	Human	Esophagus	ESCC	1.06e-13	5.33e-01	0.0811
84897	TBRG1	LZE7T	Human	Esophagus	ESCC	2.51e-10	6.52e-01	0.0667
84897	TBRG1	LZE8T	Human	Esophagus	ESCC	6.86e-08	2.43e-01	0.067
84897	TBRG1	LZE20T	Human	Esophagus	ESCC	4.00e-09	3.75e-01	0.0662
84897	TBRG1	LZE24T	Human	Esophagus	ESCC	2.77e-41	1.25e+00	0.0596
84897	TBRG1	P1T-E	Human	Esophagus	ESCC	2.09e-10	6.42e-01	0.0875
84897	TBRG1	P2T-E	Human	Esophagus	ESCC	4.70e-15	2.45e-01	0.1177
84897	TBRG1	P4T-E	Human	Esophagus	ESCC	3.43e-59	1.37e+00	0.1323
84897	TBRG1	P5T-E	Human	Esophagus	ESCC	5.96e-32	4.90e-01	0.1327
84897	TBRG1	P8T-E	Human	Esophagus	ESCC	3.33e-49	8.72e-01	0.0889
84897	TBRG1	P9T-E	Human	Esophagus	ESCC	4.11e-30	7.08e-01	0.1131
84897	TBRG1	P10T-E	Human	Esophagus	ESCC	3.39e-37	7.43e-01	0.116
84897	TBRG1	P11T-E	Human	Esophagus	ESCC	9.50e-30	1.15e+00	0.1426
84897	TBRG1	P12T-E	Human	Esophagus	ESCC	3.52e-54	9.05e-01	0.1122
84897	TBRG1	P15T-E	Human	Esophagus	ESCC	2.64e-18	4.19e-01	0.1149
84897	TBRG1	P16T-E	Human	Esophagus	ESCC	3.90e-30	5.42e-01	0.1153
84897	TBRG1	P17T-E	Human	Esophagus	ESCC	3.91e-04	4.63e-01	0.1278
84897	TBRG1	P19T-E	Human	Esophagus	ESCC	6.37e-04	7.44e-01	0.1662
84897	TBRG1	P20T-E	Human	Esophagus	ESCC	5.85e-28	5.68e-01	0.1124
84897	TBRG1	P21T-E	Human	Esophagus	ESCC	7.36e-55	1.15e+00	0.1617

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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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:0031647111	Esophagus	ESCC	regulation of protein stability	223/8552	298/18723	5.76e-25	1.52e-22	223
GO:003450418	Esophagus	ESCC	protein localization to nucleus	211/8552	290/18723	4.06e-21	6.60e-19	211
GO:00062604	Esophagus	ESCC	DNA replication	181/8552	260/18723	3.55e-15	2.05e-13	181
GO:0050821111	Esophagus	ESCC	protein stabilization	140/8552	191/18723	6.50e-15	3.61e-13	140
GO:199017316	Esophagus	ESCC	protein localization to nucleoplasm	14/8552	14/18723	1.71e-05	1.52e-04	14
GO:00316477	Liver	NAFLD	regulation of protein stability	61/1882	298/18723	5.00e-08	4.71e-06	61
GO:00508217	Liver	NAFLD	protein stabilization	40/1882	191/18723	5.38e-06	1.95e-04	40
GO:00345046	Liver	NAFLD	protein localization to nucleus	45/1882	290/18723	2.16e-03	2.10e-02	45
GO:003164712	Liver	Cirrhotic	regulation of protein stability	144/4634	298/18723	6.74e-19	1.28e-16	144
GO:005082112	Liver	Cirrhotic	protein stabilization	97/4634	191/18723	6.67e-15	6.97e-13	97
GO:003450411	Liver	Cirrhotic	protein localization to nucleus	113/4634	290/18723	5.00e-08	1.58e-06	113
GO:19901733	Liver	Cirrhotic	protein localization to nucleoplasm	12/4634	14/18723	2.84e-06	5.08e-05	12
GO:003164722	Liver	HCC	regulation of protein stability	211/7958	298/18723	2.29e-23	5.01e-21	211
GO:005082122	Liver	HCC	protein stabilization	139/7958	191/18723	1.61e-17	1.71e-15	139
GO:003450421	Liver	HCC	protein localization to nucleus	194/7958	290/18723	2.84e-17	2.85e-15	194
GO:00062601	Liver	HCC	DNA replication	146/7958	260/18723	5.68e-06	7.02e-05	146
GO:199017311	Liver	HCC	protein localization to nucleoplasm	13/7958	14/18723	1.25e-04	1.03e-03	13
GO:00316478	Lung	IAC	regulation of protein stability	62/2061	298/18723	5.37e-07	3.32e-05	62
GO:00345047	Lung	IAC	protein localization to nucleus	50/2061	290/18723	8.71e-04	1.11e-02	50
GO:00508218	Lung	IAC	protein stabilization	34/2061	191/18723	3.21e-03	2.78e-02	34

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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

TBRG1

SNV

Missense_Mutation

c.985G>A

p.Asp329Asn

p.D329N

Q3YBR2

protein_coding

tolerated(0.15)

benign(0.015)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TBRG1

insertion

Nonsense_Mutation

novel

c.988_989insCATCCACAACCTGATCCAGAGCTGTCCAGGAGCTCGAAAATGCATCAA

p.Gly330delinsAlaSerThrThrTerSerArgAlaValGlnGluLeuGluAsnAlaSerArg

p.G330delinsASTT*SRAVQELENASR

Q3YBR2

protein_coding

TCGA-A2-A0D1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

taxotere

TBRG1

insertion

Frame_Shift_Ins

novel

c.681_682insTTCAAAACATTTAAGCAATCCTCAC

p.Pro228PhefsTer29

p.P228Ffs*29

Q3YBR2

protein_coding

TCGA-AN-A04D-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TBRG1

insertion

Nonsense_Mutation

novel

c.1041_1042insCCTCTCTCCTTCCTTCTTGAGGATTGATCTCATTGCTCG

p.Ala347_Phe348insProLeuSerPheLeuLeuGluAspTerSerHisCysSer

p.A347_F348insPLSFLLED*SHCS

Q3YBR2

protein_coding

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

TBRG1

insertion

Nonsense_Mutation

novel

c.281_282insCACTGCCCAGGGCTCGGAAAGAACGATACTTTGA

p.Ala95ThrfsTer11

p.A95Tfs*11

Q3YBR2

protein_coding

TCGA-B6-A0I8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TBRG1

SNV

Missense_Mutation

c.469N>C

p.Cys157Arg

p.C157R

Q3YBR2

protein_coding

tolerated(0.16)

benign(0.013)

TCGA-JX-A3Q8-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TBRG1

SNV

Missense_Mutation

rs766145884

c.538N>T

p.Arg180Trp

p.R180W

Q3YBR2

protein_coding

deleterious(0.01)

possibly_damaging(0.727)

TCGA-AA-3877-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

TBRG1

SNV

Missense_Mutation

novel

c.857T>G

p.Leu286Arg

p.L286R

Q3YBR2

protein_coding

tolerated(0.26)

benign(0.125)

TCGA-AA-A02R-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

TBRG1

SNV

Missense_Mutation

rs761393184

c.500G>A

p.Arg167His

p.R167H

Q3YBR2

protein_coding

deleterious(0)

probably_damaging(0.972)

TCGA-AZ-4315-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

TBRG1

SNV

Missense_Mutation

novel

c.184N>A

p.Leu62Ile

p.L62I

Q3YBR2

protein_coding

tolerated(0.17)

benign(0.158)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

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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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