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: RHOBTB3

Gene summary for RHOBTB3

Gene summary.

Gene information	Species	Human
	Gene symbol	RHOBTB3
	Gene ID	22836
	Gene name	Rho related BTB domain containing 3
	Gene Alias	RHOBTB3
	Cytomap	5q15
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	O94955

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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
22836	RHOBTB3	GSM4909281	Human	Breast	IDC	4.57e-02	1.97e-01	0.21
22836	RHOBTB3	GSM4909285	Human	Breast	IDC	4.60e-14	3.54e-01	0.21
22836	RHOBTB3	GSM4909286	Human	Breast	IDC	1.55e-23	4.09e-01	0.1081
22836	RHOBTB3	GSM4909296	Human	Breast	IDC	6.20e-05	-1.88e-01	0.1524
22836	RHOBTB3	GSM4909297	Human	Breast	IDC	3.79e-02	-1.32e-01	0.1517
22836	RHOBTB3	GSM4909301	Human	Breast	IDC	3.06e-33	8.02e-01	0.1577
22836	RHOBTB3	GSM4909307	Human	Breast	IDC	3.81e-52	1.04e+00	0.1569
22836	RHOBTB3	GSM4909308	Human	Breast	IDC	1.56e-109	1.44e+00	0.158
22836	RHOBTB3	GSM4909311	Human	Breast	IDC	3.84e-07	-2.05e-01	0.1534
22836	RHOBTB3	GSM4909312	Human	Breast	IDC	3.84e-07	-2.05e-01	0.1552
22836	RHOBTB3	GSM4909319	Human	Breast	IDC	8.25e-07	-1.98e-01	0.1563
22836	RHOBTB3	DCIS2	Human	Breast	DCIS	1.54e-04	-1.88e-01	0.0085
22836	RHOBTB3	HTA11_99999970781_79442	Human	Colorectum	MSS	1.53e-06	-3.37e-01	0.294
22836	RHOBTB3	HTA11_99999973899_84307	Human	Colorectum	MSS	1.96e-09	-7.21e-01	0.2585
22836	RHOBTB3	HTA11_99999974143_84620	Human	Colorectum	MSS	1.59e-02	-2.61e-01	0.3005
22836	RHOBTB3	A001-C-207	Human	Colorectum	FAP	4.54e-02	-1.86e-01	0.1278
22836	RHOBTB3	A015-C-203	Human	Colorectum	FAP	3.10e-24	-4.00e-01	-0.1294
22836	RHOBTB3	A015-C-204	Human	Colorectum	FAP	5.24e-05	-2.28e-01	-0.0228
22836	RHOBTB3	A014-C-040	Human	Colorectum	FAP	1.41e-03	-2.88e-01	-0.1184
22836	RHOBTB3	A002-C-201	Human	Colorectum	FAP	1.83e-10	-1.69e-01	0.0324

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
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
Prostate		BPH: Benign Prostatic Hyperplasia
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:001648210	Esophagus	ESCC	cytosolic transport	124/8552	168/18723	9.69e-14	4.69e-12	124
GO:000716320	Esophagus	ESCC	establishment or maintenance of cell polarity	143/8552	218/18723	2.05e-09	4.65e-08	143
GO:000701527	Esophagus	ESCC	actin filament organization	259/8552	442/18723	2.37e-08	4.50e-07	259
GO:0061458110	Esophagus	ESCC	reproductive system development	247/8552	427/18723	2.24e-07	3.42e-06	247
GO:004860818	Esophagus	ESCC	reproductive structure development	245/8552	424/18723	2.82e-07	4.14e-06	245
GO:0032970111	Esophagus	ESCC	regulation of actin filament-based process	231/8552	397/18723	2.91e-07	4.20e-06	231
GO:0032956111	Esophagus	ESCC	regulation of actin cytoskeleton organization	210/8552	358/18723	4.40e-07	6.00e-06	210
GO:00421477	Esophagus	ESCC	retrograde transport, endosome to Golgi	63/8552	91/18723	4.58e-06	4.87e-05	63
GO:002260420	Esophagus	ESCC	regulation of cell morphogenesis	180/8552	309/18723	5.19e-06	5.45e-05	180
GO:003086517	Esophagus	ESCC	cortical cytoskeleton organization	44/8552	61/18723	2.50e-05	2.13e-04	44
GO:000836018	Esophagus	ESCC	regulation of cell shape	92/8552	154/18723	3.00e-04	1.81e-03	92
GO:00226047	Liver	NAFLD	regulation of cell morphogenesis	62/1882	309/18723	8.35e-08	7.09e-06	62
GO:00070157	Liver	NAFLD	actin filament organization	78/1882	442/18723	5.44e-07	3.21e-05	78
GO:00071636	Liver	NAFLD	establishment or maintenance of cell polarity	46/1882	218/18723	8.80e-07	4.60e-05	46
GO:00329707	Liver	NAFLD	regulation of actin filament-based process	66/1882	397/18723	2.92e-05	7.72e-04	66
GO:00329567	Liver	NAFLD	regulation of actin cytoskeleton organization	60/1882	358/18723	5.20e-05	1.20e-03	60
GO:00164825	Liver	NAFLD	cytosolic transport	34/1882	168/18723	5.52e-05	1.25e-03	34
GO:00161975	Liver	NAFLD	endosomal transport	41/1882	230/18723	2.02e-04	3.53e-03	41
GO:00421474	Liver	NAFLD	retrograde transport, endosome to Golgi	19/1882	91/18723	1.55e-03	1.67e-02	19
GO:00083606	Liver	NAFLD	regulation of cell shape	27/1882	154/18723	2.92e-03	2.65e-02	27

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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

RHOBTB3

SNV

Missense_Mutation

c.1325N>T

p.Cys442Phe

p.C442F

O94955

protein_coding

deleterious(0.01)

probably_damaging(0.995)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

RHOBTB3

SNV

Missense_Mutation

c.1099G>C

p.Asp367His

p.D367H

O94955

protein_coding

tolerated(0.07)

benign(0.02)

TCGA-A8-A06U-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RHOBTB3

SNV

Missense_Mutation

c.1726N>C

p.Glu576Gln

p.E576Q

O94955

protein_coding

deleterious(0.02)

possibly_damaging(0.71)

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

RHOBTB3

SNV

Missense_Mutation

c.1726N>A

p.Glu576Lys

p.E576K

O94955

protein_coding

deleterious(0.02)

possibly_damaging(0.535)

TCGA-GM-A2D9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

RHOBTB3

insertion

Nonsense_Mutation

novel

c.457_458insCTCTGCTTGTTCCTGATTAAATGGTTAAT

p.Gly153AlafsTer7

p.G153Afs*7

O94955

protein_coding

TCGA-A2-A0EV-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RHOBTB3

insertion

In_Frame_Ins

novel

c.1033_1034insTTTACTTTTACCTTT

p.Arg345delinsLeuTyrPheTyrLeuCys

p.R345delinsLYFYLC

O94955

protein_coding

TCGA-AR-A0U2-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

tamoxiphen

RHOBTB3

deletion

Frame_Shift_Del

novel

c.48delN

p.Gln17ArgfsTer28

p.Q17Rfs*28

O94955

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

RHOBTB3

SNV

Missense_Mutation

novel

c.1371N>C

p.Lys457Asn

p.K457N

O94955

protein_coding

tolerated(0.6)

benign(0.003)

TCGA-C5-A8XJ-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

RHOBTB3

SNV

Missense_Mutation

rs148767115

c.1784N>T

p.Ala595Val

p.A595V

O94955

protein_coding

deleterious(0.02)

possibly_damaging(0.46)

TCGA-IR-A3LK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

RHOBTB3

SNV

Missense_Mutation

c.1325G>A

p.Cys442Tyr

p.C442Y

O94955

protein_coding

tolerated(0.06)

probably_damaging(0.995)

TCGA-3L-AA1B-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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