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: RAB3GAP2

Gene summary for RAB3GAP2

Gene summary.

Gene information	Species	Human
	Gene symbol	RAB3GAP2
	Gene ID	25782
	Gene name	RAB3 GTPase activating non-catalytic protein subunit 2
	Gene Alias	MARTS1
	Cytomap	1q41
	Gene Type	protein-coding
	GO ID	GO:0000045
	UniProtAcc	Q9H2M9

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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
25782	RAB3GAP2	CCI_1	Human	Cervix	CC	1.07e-07	1.05e+00	0.528
25782	RAB3GAP2	CCI_2	Human	Cervix	CC	4.99e-04	6.70e-01	0.5249
25782	RAB3GAP2	CCI_3	Human	Cervix	CC	1.62e-13	9.41e-01	0.516
25782	RAB3GAP2	LZE2T	Human	Esophagus	ESCC	8.31e-06	3.77e-01	0.082
25782	RAB3GAP2	LZE4T	Human	Esophagus	ESCC	6.55e-12	2.29e-01	0.0811
25782	RAB3GAP2	LZE5T	Human	Esophagus	ESCC	8.85e-03	2.74e-01	0.0514
25782	RAB3GAP2	LZE7T	Human	Esophagus	ESCC	4.65e-13	5.44e-01	0.0667
25782	RAB3GAP2	LZE24T	Human	Esophagus	ESCC	1.92e-21	3.26e-01	0.0596
25782	RAB3GAP2	LZE21T	Human	Esophagus	ESCC	4.27e-07	2.55e-01	0.0655
25782	RAB3GAP2	P1T-E	Human	Esophagus	ESCC	2.18e-18	5.95e-01	0.0875
25782	RAB3GAP2	P2T-E	Human	Esophagus	ESCC	9.39e-28	3.55e-01	0.1177
25782	RAB3GAP2	P4T-E	Human	Esophagus	ESCC	9.32e-12	1.40e-01	0.1323
25782	RAB3GAP2	P5T-E	Human	Esophagus	ESCC	5.02e-09	1.96e-01	0.1327
25782	RAB3GAP2	P8T-E	Human	Esophagus	ESCC	4.89e-17	3.56e-01	0.0889
25782	RAB3GAP2	P9T-E	Human	Esophagus	ESCC	1.96e-14	2.32e-01	0.1131
25782	RAB3GAP2	P10T-E	Human	Esophagus	ESCC	8.06e-17	3.63e-01	0.116
25782	RAB3GAP2	P11T-E	Human	Esophagus	ESCC	2.93e-10	3.89e-01	0.1426
25782	RAB3GAP2	P12T-E	Human	Esophagus	ESCC	2.20e-12	1.93e-01	0.1122
25782	RAB3GAP2	P15T-E	Human	Esophagus	ESCC	1.99e-22	3.88e-01	0.1149
25782	RAB3GAP2	P16T-E	Human	Esophagus	ESCC	1.07e-25	2.93e-01	0.1153

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
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:190211521	Oral cavity	EOLP	regulation of organelle assembly	43/2218	186/18723	1.11e-05	1.94e-04	43
GO:001623911	Oral cavity	EOLP	positive regulation of macroautophagy	20/2218	63/18723	2.32e-05	3.50e-04	20
GO:007097223	Oral cavity	EOLP	protein localization to endoplasmic reticulum	22/2218	74/18723	2.93e-05	4.23e-04	22
GO:004308714	Oral cavity	EOLP	regulation of GTPase activity	66/2218	348/18723	6.92e-05	8.55e-04	66
GO:007259921	Oral cavity	EOLP	establishment of protein localization to endoplasmic reticulum	15/2218	46/18723	1.71e-04	1.78e-03	15
GO:00440901	Oral cavity	EOLP	positive regulation of vacuole organization	7/2218	13/18723	2.90e-04	2.74e-03	7
GO:000703321	Oral cavity	EOLP	vacuole organization	37/2218	180/18723	5.45e-04	4.67e-03	37
GO:00440882	Oral cavity	EOLP	regulation of vacuole organization	12/2218	45/18723	5.03e-03	2.65e-02	12
GO:000004521	Oral cavity	EOLP	autophagosome assembly	21/2218	99/18723	5.46e-03	2.83e-02	21
GO:009015022	Oral cavity	EOLP	establishment of protein localization to membrane	45/2218	260/18723	5.73e-03	2.94e-02	45
GO:2000786	Oral cavity	EOLP	positive regulation of autophagosome assembly	5/2218	11/18723	5.79e-03	2.94e-02	5
GO:19050372	Oral cavity	EOLP	autophagosome organization	21/2218	103/18723	8.70e-03	4.05e-02	21
GO:000989633	Oral cavity	NEOLP	positive regulation of catabolic process	111/2005	492/18723	1.19e-14	4.72e-12	111
GO:003133133	Oral cavity	NEOLP	positive regulation of cellular catabolic process	97/2005	427/18723	3.77e-13	1.07e-10	97
GO:007259432	Oral cavity	NEOLP	establishment of protein localization to organelle	84/2005	422/18723	1.30e-08	6.10e-07	84
GO:001050631	Oral cavity	NEOLP	regulation of autophagy	60/2005	317/18723	8.06e-06	1.57e-04	60
GO:001623631	Oral cavity	NEOLP	macroautophagy	54/2005	291/18723	3.95e-05	5.62e-04	54
GO:001623921	Oral cavity	NEOLP	positive regulation of macroautophagy	17/2005	63/18723	2.45e-04	2.54e-03	17
GO:000703331	Oral cavity	NEOLP	vacuole organization	35/2005	180/18723	3.44e-04	3.33e-03	35
GO:001050831	Oral cavity	NEOLP	positive regulation of autophagy	26/2005	124/18723	5.88e-04	5.08e-03	26

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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

RAB3GAP2

SNV

Missense_Mutation

c.1387N>G

p.Gln463Glu

p.Q463E

Q9H2M9

protein_coding

deleterious(0.02)

possibly_damaging(0.576)

TCGA-AC-A2FG-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

RAB3GAP2

SNV

Missense_Mutation

c.2945N>C

p.Val982Ala

p.V982A

Q9H2M9

protein_coding

tolerated(0.74)

benign(0)

TCGA-AN-A0XV-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

RAB3GAP2

SNV

Missense_Mutation

novel

c.98N>A

p.Ala33Asp

p.A33D

Q9H2M9

protein_coding

tolerated_low_confidence(0.36)

benign(0.165)

TCGA-B6-A0IA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

RAB3GAP2

SNV

Missense_Mutation

c.2222N>G

p.Phe741Cys

p.F741C

Q9H2M9

protein_coding

deleterious(0.01)

probably_damaging(0.935)

TCGA-BH-A0AZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

RAB3GAP2

SNV

Missense_Mutation

c.3200N>T

p.Ser1067Phe

p.S1067F

Q9H2M9

protein_coding

deleterious(0)

probably_damaging(0.984)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

RAB3GAP2

SNV

Missense_Mutation

c.2416G>A

p.Val806Met

p.V806M

Q9H2M9

protein_coding

tolerated(0.25)

possibly_damaging(0.875)

TCGA-BH-A0BZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

RAB3GAP2

SNV

Missense_Mutation

c.3859N>A

p.Gly1287Arg

p.G1287R

Q9H2M9

protein_coding

deleterious(0)

possibly_damaging(0.894)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

RAB3GAP2

SNV

Missense_Mutation

c.3476C>G

p.Ser1159Cys

p.S1159C

Q9H2M9

protein_coding

tolerated(0.18)

benign(0.003)

TCGA-C8-A1HM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

RAB3GAP2

SNV

Missense_Mutation

c.1847N>C

p.Leu616Ser

p.L616S

Q9H2M9

protein_coding

deleterious(0.02)

benign(0.035)

TCGA-E2-A15A-06

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

RAB3GAP2

insertion

Frame_Shift_Ins

novel

c.1276_1277insTCCTTGTTCTAATATTTTTACCATATTG

p.Arg426LeufsTer25

p.R426Lfs*25

Q9H2M9

protein_coding

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

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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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