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: RAB25

Gene summary for RAB25

Gene summary.

Gene information	Species	Human
	Gene symbol	RAB25
	Gene ID	57111
	Gene name	RAB25, member RAS oncogene family
	Gene Alias	CATX-8
	Cytomap	1q22
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	P57735

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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
57111	RAB25	GSM4909285	Human	Breast	IDC	2.16e-07	3.86e-01	0.21
57111	RAB25	GSM4909286	Human	Breast	IDC	3.87e-02	-1.41e-01	0.1081
57111	RAB25	GSM4909293	Human	Breast	IDC	3.24e-02	2.65e-01	0.1581
57111	RAB25	GSM4909296	Human	Breast	IDC	5.87e-07	5.39e-02	0.1524
57111	RAB25	GSM4909297	Human	Breast	IDC	2.55e-14	-1.70e-01	0.1517
57111	RAB25	GSM4909298	Human	Breast	IDC	5.85e-03	2.07e-01	0.1551
57111	RAB25	GSM4909301	Human	Breast	IDC	1.16e-06	-2.67e-01	0.1577
57111	RAB25	GSM4909311	Human	Breast	IDC	5.39e-25	-1.56e-01	0.1534
57111	RAB25	GSM4909312	Human	Breast	IDC	4.48e-11	7.57e-02	0.1552
57111	RAB25	GSM4909315	Human	Breast	IDC	1.71e-06	4.02e-01	0.21
57111	RAB25	GSM4909316	Human	Breast	IDC	5.99e-14	5.55e-01	0.21
57111	RAB25	GSM4909317	Human	Breast	IDC	1.77e-03	3.18e-01	0.1355
57111	RAB25	GSM4909318	Human	Breast	IDC	9.45e-03	2.93e-01	0.2031
57111	RAB25	GSM4909319	Human	Breast	IDC	3.93e-40	-1.63e-01	0.1563
57111	RAB25	GSM4909320	Human	Breast	IDC	6.73e-06	-6.66e-02	0.1575
57111	RAB25	GSM4909321	Human	Breast	IDC	5.98e-15	6.20e-02	0.1559
57111	RAB25	M2	Human	Breast	IDC	1.42e-05	3.79e-01	0.21
57111	RAB25	NCCBC11	Human	Breast	DCIS	1.73e-08	3.81e-01	0.1232
57111	RAB25	NCCBC14	Human	Breast	DCIS	2.01e-27	4.81e-01	0.2021
57111	RAB25	NCCBC5	Human	Breast	DCIS	1.32e-07	-1.67e-01	0.2046

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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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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
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:000166714	Breast	IDC	ameboidal-type cell migration	64/1434	475/18723	6.65e-06	2.05e-04	64
GO:001063112	Breast	IDC	epithelial cell migration	51/1434	357/18723	1.14e-05	3.08e-04	51
GO:009013212	Breast	IDC	epithelium migration	51/1434	360/18723	1.44e-05	3.70e-04	51
GO:009013012	Breast	IDC	tissue migration	51/1434	365/18723	2.11e-05	5.11e-04	51
GO:001063212	Breast	IDC	regulation of epithelial cell migration	43/1434	292/18723	2.61e-05	6.17e-04	43
GO:001063413	Breast	IDC	positive regulation of epithelial cell migration	30/1434	176/18723	2.76e-05	6.50e-04	30
GO:000206414	Breast	IDC	epithelial cell development	28/1434	220/18723	5.53e-03	4.05e-02	28
GO:001063121	Breast	DCIS	epithelial cell migration	51/1390	357/18723	4.83e-06	1.43e-04	51
GO:009013221	Breast	DCIS	epithelium migration	51/1390	360/18723	6.14e-06	1.75e-04	51
GO:009013021	Breast	DCIS	tissue migration	51/1390	365/18723	9.09e-06	2.45e-04	51
GO:000166723	Breast	DCIS	ameboidal-type cell migration	62/1390	475/18723	9.60e-06	2.56e-04	62
GO:001063221	Breast	DCIS	regulation of epithelial cell migration	43/1390	292/18723	1.23e-05	3.13e-04	43
GO:001063422	Breast	DCIS	positive regulation of epithelial cell migration	30/1390	176/18723	1.53e-05	3.75e-04	30
GO:0002064	Colorectum	AD	epithelial cell development	89/3918	220/18723	2.98e-11	3.52e-09	89
GO:0001667	Colorectum	AD	ameboidal-type cell migration	137/3918	475/18723	2.17e-05	4.33e-04	137
GO:0090132	Colorectum	AD	epithelium migration	105/3918	360/18723	1.18e-04	1.73e-03	105
GO:0010632	Colorectum	AD	regulation of epithelial cell migration	88/3918	292/18723	1.19e-04	1.75e-03	88
GO:0010631	Colorectum	AD	epithelial cell migration	104/3918	357/18723	1.33e-04	1.90e-03	104
GO:0090130	Colorectum	AD	tissue migration	105/3918	365/18723	2.10e-04	2.77e-03	105
GO:0010634	Colorectum	AD	positive regulation of epithelial cell migration	56/3918	176/18723	4.51e-04	5.03e-03	56

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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

RAB25

SNV

Missense_Mutation

c.363G>A

p.Met121Ile

p.M121I

P57735

protein_coding

deleterious_low_confidence(0.03)

probably_damaging(0.978)

TCGA-A8-A07W-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

exemestane

RAB25

SNV

Missense_Mutation

c.262G>A

p.Ala88Thr

p.A88T

P57735

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.998)

TCGA-BH-A0B1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

adriamycin

RAB25

SNV

Missense_Mutation

rs368546153

c.358G>A

p.Val120Ile

p.V120I

P57735

protein_coding

tolerated_low_confidence(1)

probably_damaging(0.985)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RAB25

SNV

Missense_Mutation

c.70N>A

p.Gly24Arg

p.G24R

P57735

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-AA-3875-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

RAB25

SNV

Missense_Mutation

c.393N>T

p.Gln131His

p.Q131H

P57735

protein_coding

tolerated_low_confidence(1)

benign(0)

TCGA-AA-3952-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Unknown

RAB25

SNV

Missense_Mutation

rs566252037

c.92N>A

p.Arg31Gln

p.R31Q

P57735

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.997)

TCGA-G4-6298-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Chemotherapy

irinotecan

RAB25

SNV

Missense_Mutation

c.142G>C

p.Glu48Gln

p.E48Q

P57735

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.997)

TCGA-AF-3913-01

Colorectum

rectum adenocarcinoma

Male

<65

III/IV

Chemotherapy

xeloda

RAB25

SNV

Missense_Mutation

novel

c.469N>A

p.Leu157Met

p.L157M

P57735

protein_coding

deleterious_low_confidence(0.03)

probably_damaging(0.998)

TCGA-A5-A0G1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

RAB25

SNV

Missense_Mutation

novel

c.130A>G

p.Thr44Ala

p.T44A

P57735

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.963)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

RAB25

SNV

Missense_Mutation

novel

c.566C>T

p.Ala189Val

p.A189V

P57735

protein_coding

tolerated_low_confidence(0.11)

benign(0.019)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

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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