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: RAC3

Gene summary for RAC3

Gene summary.

Gene information	Species	Human
	Gene symbol	RAC3
	Gene ID	5881
	Gene name	Rac family small GTPase 3
	Gene Alias	RAC3
	Cytomap	17q25.3
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	P60763

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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
5881	RAC3	LZE4T	Human	Esophagus	ESCC	6.89e-04	2.09e-01	0.0811
5881	RAC3	LZE22T	Human	Esophagus	ESCC	4.79e-12	1.24e+00	0.068
5881	RAC3	LZE24T	Human	Esophagus	ESCC	5.83e-10	2.88e-01	0.0596
5881	RAC3	P1T-E	Human	Esophagus	ESCC	6.42e-06	2.90e-01	0.0875
5881	RAC3	P2T-E	Human	Esophagus	ESCC	1.37e-105	2.00e+00	0.1177
5881	RAC3	P4T-E	Human	Esophagus	ESCC	1.45e-24	5.31e-01	0.1323
5881	RAC3	P5T-E	Human	Esophagus	ESCC	3.82e-14	2.50e-01	0.1327
5881	RAC3	P8T-E	Human	Esophagus	ESCC	6.49e-09	1.17e-01	0.0889
5881	RAC3	P9T-E	Human	Esophagus	ESCC	1.36e-06	2.42e-01	0.1131
5881	RAC3	P10T-E	Human	Esophagus	ESCC	1.14e-44	8.78e-01	0.116
5881	RAC3	P11T-E	Human	Esophagus	ESCC	3.85e-18	9.24e-01	0.1426
5881	RAC3	P12T-E	Human	Esophagus	ESCC	2.20e-68	1.33e+00	0.1122
5881	RAC3	P15T-E	Human	Esophagus	ESCC	3.76e-30	6.59e-01	0.1149
5881	RAC3	P16T-E	Human	Esophagus	ESCC	1.06e-58	9.94e-01	0.1153
5881	RAC3	P20T-E	Human	Esophagus	ESCC	2.78e-97	2.71e+00	0.1124
5881	RAC3	P21T-E	Human	Esophagus	ESCC	4.38e-60	1.34e+00	0.1617
5881	RAC3	P22T-E	Human	Esophagus	ESCC	5.30e-03	5.75e-02	0.1236
5881	RAC3	P23T-E	Human	Esophagus	ESCC	2.01e-15	5.09e-01	0.108
5881	RAC3	P24T-E	Human	Esophagus	ESCC	8.84e-29	6.14e-01	0.1287
5881	RAC3	P26T-E	Human	Esophagus	ESCC	1.99e-51	9.64e-01	0.1276

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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
Liver		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
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:001605517	Esophagus	ESCC	Wnt signaling pathway	268/8552	444/18723	2.32e-10	6.58e-09	268
GO:019873817	Esophagus	ESCC	cell-cell signaling by wnt	269/8552	446/18723	2.41e-10	6.79e-09	269
GO:000716320	Esophagus	ESCC	establishment or maintenance of cell polarity	143/8552	218/18723	2.05e-09	4.65e-08	143
GO:003158919	Esophagus	ESCC	cell-substrate adhesion	221/8552	363/18723	3.06e-09	6.62e-08	221
GO:001081020	Esophagus	ESCC	regulation of cell-substrate adhesion	144/8552	221/18723	3.55e-09	7.45e-08	144
GO:000701527	Esophagus	ESCC	actin filament organization	259/8552	442/18723	2.37e-08	4.50e-07	259
GO:004578527	Esophagus	ESCC	positive regulation of cell adhesion	255/8552	437/18723	5.07e-08	9.11e-07	255
GO:0032970111	Esophagus	ESCC	regulation of actin filament-based process	231/8552	397/18723	2.91e-07	4.20e-06	231
GO:001081126	Esophagus	ESCC	positive regulation of cell-substrate adhesion	84/8552	123/18723	3.18e-07	4.50e-06	84
GO:0032956111	Esophagus	ESCC	regulation of actin cytoskeleton organization	210/8552	358/18723	4.40e-07	6.00e-06	210
GO:0048872111	Esophagus	ESCC	homeostasis of number of cells	163/8552	272/18723	1.40e-06	1.69e-05	163
GO:002260420	Esophagus	ESCC	regulation of cell morphogenesis	180/8552	309/18723	5.19e-06	5.45e-05	180
GO:001072010	Esophagus	ESCC	positive regulation of cell development	172/8552	298/18723	1.74e-05	1.55e-04	172
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:001076920	Esophagus	ESCC	regulation of cell morphogenesis involved in differentiation	61/8552	96/18723	3.12e-04	1.85e-03	61
GO:001077018	Esophagus	ESCC	positive regulation of cell morphogenesis involved in differentiation	51/8552	79/18723	5.48e-04	3.00e-03	51
GO:190002420	Esophagus	ESCC	regulation of substrate adhesion-dependent cell spreading	38/8552	57/18723	1.11e-03	5.56e-03	38
GO:003444620	Esophagus	ESCC	substrate adhesion-dependent cell spreading	65/8552	108/18723	1.67e-03	7.72e-03	65
GO:190002620	Esophagus	ESCC	positive regulation of substrate adhesion-dependent cell spreading	28/8552	41/18723	2.88e-03	1.21e-02	28

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05418211	Esophagus	ESCC	Fluid shear stress and atherosclerosis	109/4205	139/8465	2.00e-12	3.72e-11	1.90e-11	109
hsa05170210	Esophagus	ESCC	Human immunodeficiency virus 1 infection	147/4205	212/8465	3.37e-09	3.53e-08	1.81e-08	147
hsa0521020	Esophagus	ESCC	Colorectal cancer	69/4205	86/8465	4.06e-09	4.13e-08	2.11e-08	69
hsa0521216	Esophagus	ESCC	Pancreatic cancer	62/4205	76/8465	7.37e-09	6.85e-08	3.51e-08	62
hsa0513526	Esophagus	ESCC	Yersinia infection	100/4205	137/8465	1.80e-08	1.59e-07	8.12e-08	100
hsa05163210	Esophagus	ESCC	Human cytomegalovirus infection	148/4205	225/8465	5.73e-07	4.00e-06	2.05e-06	148
hsa0452030	Esophagus	ESCC	Adherens junction	69/4205	93/8465	1.08e-06	6.83e-06	3.50e-06	69
hsa0407116	Esophagus	ESCC	Sphingolipid signaling pathway	85/4205	121/8465	3.04e-06	1.73e-05	8.84e-06	85
hsa0451020	Esophagus	ESCC	Focal adhesion	127/4205	203/8465	1.25e-04	4.99e-04	2.56e-04	127
hsa0541630	Esophagus	ESCC	Viral myocarditis	41/4205	60/8465	2.59e-03	7.05e-03	3.61e-03	41
hsa0436016	Esophagus	ESCC	Axon guidance	108/4205	182/8465	5.13e-03	1.30e-02	6.67e-03	108
hsa0481028	Esophagus	ESCC	Regulation of actin cytoskeleton	133/4205	229/8465	5.94e-03	1.48e-02	7.56e-03	133
hsa052319	Esophagus	ESCC	Choline metabolism in cancer	61/4205	98/8465	7.97e-03	1.92e-02	9.84e-03	61
hsa05418310	Esophagus	ESCC	Fluid shear stress and atherosclerosis	109/4205	139/8465	2.00e-12	3.72e-11	1.90e-11	109
hsa0517038	Esophagus	ESCC	Human immunodeficiency virus 1 infection	147/4205	212/8465	3.37e-09	3.53e-08	1.81e-08	147
hsa05210110	Esophagus	ESCC	Colorectal cancer	69/4205	86/8465	4.06e-09	4.13e-08	2.11e-08	69
hsa0521217	Esophagus	ESCC	Pancreatic cancer	62/4205	76/8465	7.37e-09	6.85e-08	3.51e-08	62
hsa05135111	Esophagus	ESCC	Yersinia infection	100/4205	137/8465	1.80e-08	1.59e-07	8.12e-08	100
hsa0516338	Esophagus	ESCC	Human cytomegalovirus infection	148/4205	225/8465	5.73e-07	4.00e-06	2.05e-06	148
hsa04520114	Esophagus	ESCC	Adherens junction	69/4205	93/8465	1.08e-06	6.83e-06	3.50e-06	69

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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

RAC3

SNV

Missense_Mutation

c.364N>T

p.Asp122Tyr

p.D122Y

P60763

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.96)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RAC3

SNV

Missense_Mutation

c.437C>G

p.Ala146Gly

p.A146G

P60763

protein_coding

deleterious_low_confidence(0.02)

benign(0.092)

TCGA-CK-4951-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

RAC3

SNV

Missense_Mutation

c.571N>A

p.Val191Ile

p.V191I

P60763

protein_coding

tolerated_low_confidence(0.64)

benign(0)

TCGA-CM-6162-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Chemotherapy

oxaliplatin

RAC3

SNV

Missense_Mutation

c.284C>T

p.Ala95Val

p.A95V

P60763

protein_coding

tolerated_low_confidence(0.09)

benign(0.192)

TCGA-F4-6856-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Ancillary

leucovorin

RAC3

SNV

Missense_Mutation

novel

c.246N>A

p.Phe82Leu

p.F82L

P60763

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.664)

TCGA-EI-6917-01

Colorectum

rectum adenocarcinoma

Male

<65

III/IV

Chemotherapy

5fluorouracil+oxaciplatina+l-folinian

RAC3

SNV

Missense_Mutation

c.193N>A

p.Asp65Asn

p.D65N

P60763

protein_coding

deleterious_low_confidence(0.01)

benign(0.445)

TCGA-A5-A0G1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

RAC3

SNV

Missense_Mutation

rs753178410

c.388N>T

p.Arg130Trp

p.R130W

P60763

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.582)

TCGA-AP-A0LS-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

RAC3

SNV

Missense_Mutation

novel

c.433N>T

p.Met145Leu

p.M145L

P60763

protein_coding

tolerated_low_confidence(1)

benign(0.009)

TCGA-DD-AADF-01

Liver

liver hepatocellular carcinoma

Female

<65

I/II

Unknown

RAC3

SNV

Missense_Mutation

novel

c.101C>T

p.Pro34Leu

p.P34L

P60763

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.941)

TCGA-D6-6516-01

Oral cavity

head & neck squamous cell carcinoma

Male

>=65

I/II

Unknown

RAC3

SNV

Missense_Mutation

novel

c.359G>T

p.Arg120Leu

p.R120L

P60763

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.995)

TCGA-F7-A624-01

Oral cavity

head & neck squamous cell carcinoma

Male

>=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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