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: RIN2

Gene summary for RIN2

Gene summary.

Gene information	Species	Human
	Gene symbol	RIN2
	Gene ID	54453
	Gene name	Ras and Rab interactor 2
	Gene Alias	MACS
	Cytomap	20p11.23
	Gene Type	protein-coding
	GO ID	GO:0001568
	UniProtAcc	Q8WYP3

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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
54453	RIN2	CA_HPV_3	Human	Cervix	CC	6.75e-03	1.66e-01	0.0414
54453	RIN2	CCI_1	Human	Cervix	CC	1.13e-04	7.76e-01	0.528
54453	RIN2	CCI_2	Human	Cervix	CC	8.72e-04	7.15e-01	0.5249
54453	RIN2	CCI_3	Human	Cervix	CC	2.97e-12	1.09e+00	0.516
54453	RIN2	T3	Human	Cervix	CC	4.56e-03	1.77e-01	0.1389
54453	RIN2	HTA11_3410_2000001011	Human	Colorectum	AD	1.06e-07	-3.15e-01	0.0155
54453	RIN2	HTA11_347_2000001011	Human	Colorectum	AD	1.96e-13	9.25e-01	-0.1954
54453	RIN2	HTA11_411_2000001011	Human	Colorectum	SER	3.85e-08	1.06e+00	-0.2602
54453	RIN2	HTA11_696_2000001011	Human	Colorectum	AD	3.38e-02	4.73e-01	-0.1464
54453	RIN2	HTA11_99999971662_82457	Human	Colorectum	MSS	6.58e-09	-3.98e-01	0.3859
54453	RIN2	HTA11_99999973899_84307	Human	Colorectum	MSS	5.93e-08	-6.69e-01	0.2585
54453	RIN2	HTA11_99999974143_84620	Human	Colorectum	MSS	2.84e-07	-4.50e-01	0.3005
54453	RIN2	A001-C-207	Human	Colorectum	FAP	7.24e-09	-3.55e-01	0.1278
54453	RIN2	A015-C-203	Human	Colorectum	FAP	1.28e-34	-6.25e-01	-0.1294
54453	RIN2	A015-C-204	Human	Colorectum	FAP	9.93e-12	-4.91e-01	-0.0228
54453	RIN2	A014-C-040	Human	Colorectum	FAP	7.36e-08	-6.60e-01	-0.1184
54453	RIN2	A002-C-201	Human	Colorectum	FAP	1.24e-22	-5.72e-01	0.0324
54453	RIN2	A002-C-203	Human	Colorectum	FAP	3.95e-03	-2.04e-01	0.2786
54453	RIN2	A001-C-119	Human	Colorectum	FAP	3.68e-10	-5.14e-01	-0.1557
54453	RIN2	A001-C-108	Human	Colorectum	FAP	1.23e-20	-4.98e-01	-0.0272

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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
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
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:001081011	Stomach	CAG with IM	regulation of cell-substrate adhesion	24/1050	221/18723	1.50e-03	1.69e-02	24
GO:001081111	Stomach	CAG with IM	positive regulation of cell-substrate adhesion	15/1050	123/18723	3.71e-03	3.28e-02	15
GO:001063411	Stomach	CAG with IM	positive regulation of epithelial cell migration	19/1050	176/18723	4.73e-03	3.86e-02	19
GO:004578521	Stomach	CSG	positive regulation of cell adhesion	47/1034	437/18723	9.72e-06	3.36e-04	47
GO:003158921	Stomach	CSG	cell-substrate adhesion	34/1034	363/18723	1.88e-03	1.99e-02	34
GO:001081021	Stomach	CSG	regulation of cell-substrate adhesion	23/1034	221/18723	2.65e-03	2.55e-02	23
GO:001063421	Stomach	CSG	positive regulation of epithelial cell migration	19/1034	176/18723	4.01e-03	3.48e-02	19
GO:000166711	Stomach	CSG	ameboidal-type cell migration	40/1034	475/18723	5.35e-03	4.31e-02	40
GO:004578531	Stomach	CAG	positive regulation of cell adhesion	30/552	437/18723	1.74e-05	6.48e-04	30
GO:00106316	Stomach	CAG	epithelial cell migration	22/552	357/18723	9.72e-04	1.41e-02	22
GO:00901326	Stomach	CAG	epithelium migration	22/552	360/18723	1.08e-03	1.48e-02	22
GO:00901306	Stomach	CAG	tissue migration	22/552	365/18723	1.29e-03	1.70e-02	22
GO:00435424	Stomach	CAG	endothelial cell migration	18/552	279/18723	1.65e-03	1.94e-02	18
GO:001063431	Stomach	CAG	positive regulation of epithelial cell migration	12/552	176/18723	6.08e-03	4.87e-02	12
GO:00106326	Stomach	CAG	regulation of epithelial cell migration	17/552	292/18723	6.18e-03	4.89e-02	17
GO:0051098113	Thyroid	PTC	regulation of binding	195/5968	363/18723	3.21e-18	3.37e-16	195
GO:0045862113	Thyroid	PTC	positive regulation of proteolysis	198/5968	372/18723	6.68e-18	6.91e-16	198
GO:0006417113	Thyroid	PTC	regulation of translation	236/5968	468/18723	2.70e-17	2.52e-15	236
GO:0022604112	Thyroid	PTC	regulation of cell morphogenesis	165/5968	309/18723	2.60e-15	1.82e-13	165
GO:0016055110	Thyroid	PTC	Wnt signaling pathway	217/5968	444/18723	3.71e-14	2.30e-12	217

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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

RIN2

SNV

Missense_Mutation

c.343N>C

p.Glu115Gln

p.E115Q

Q8WYP3

protein_coding

tolerated_low_confidence(0.16)

benign(0.023)

TCGA-A1-A0SO-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

RIN2

SNV

Missense_Mutation

c.1117C>G

p.Arg373Gly

p.R373G

Q8WYP3

protein_coding

tolerated(0.39)

benign(0)

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

RIN2

SNV

Missense_Mutation

novel

c.2069T>G

p.Val690Gly

p.V690G

Q8WYP3

protein_coding

deleterious(0)

probably_damaging(0.958)

TCGA-A7-A0DA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

RIN2

SNV

Missense_Mutation

c.654N>G

p.Phe218Leu

p.F218L

Q8WYP3

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-AN-A0FT-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

RIN2

SNV

Missense_Mutation

novel

c.2069N>G

p.Val690Gly

p.V690G

Q8WYP3

protein_coding

deleterious(0)

probably_damaging(0.958)

TCGA-BH-A1F8-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

RIN2

SNV

Missense_Mutation

novel

c.2069T>G

p.Val690Gly

p.V690G

Q8WYP3

protein_coding

deleterious(0)

probably_damaging(0.958)

TCGA-D8-A1XG-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

RIN2

SNV

Missense_Mutation

novel

c.2069N>G

p.Val690Gly

p.V690G

Q8WYP3

protein_coding

deleterious(0)

probably_damaging(0.958)

TCGA-D8-A1XO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

RIN2

insertion

Frame_Shift_Ins

novel

c.1867_1868insAGGAAGGAGAATCACTTGAACCTGGGAGGTGG

p.Leu623GlnfsTer19

p.L623Qfs*19

Q8WYP3

protein_coding

TCGA-BH-A0B1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

adriamycin

RIN2

insertion

In_Frame_Ins

novel

c.1805_1806insACTTCCTCCTCC

p.Met602delinsIleLeuProProPro

p.M602delinsILPPP

Q8WYP3

protein_coding

TCGA-BH-A0BJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

RIN2

insertion

Frame_Shift_Ins

novel

c.1806_1807insACTCGCTGGAGTTCGACCGGAGCATGCCT

p.Leu603ThrfsTer18

p.L603Tfs*18

Q8WYP3

protein_coding

TCGA-BH-A0BJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

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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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