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: RGS1

Gene summary for RGS1

Gene summary.

Gene information	Species	Human
	Gene symbol	RGS1
	Gene ID	5996
	Gene name	regulator of G protein signaling 1
	Gene Alias	1R20
	Cytomap	1q31.2
	Gene Type	protein-coding
	GO ID	GO:0002376
	UniProtAcc	A0A024R945

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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
5996	RGS1	GSM4909295	Human	Breast	IDC	3.96e-03	3.00e-01	0.0898
5996	RGS1	GSM4909305	Human	Breast	IDC	1.82e-03	2.43e-01	0.0436
5996	RGS1	GSM4909317	Human	Breast	IDC	7.56e-06	2.45e-01	0.1355
5996	RGS1	M1	Human	Breast	IDC	3.54e-06	2.81e-01	0.1577
5996	RGS1	NCCBC11	Human	Breast	DCIS	4.13e-03	5.22e-01	0.1232
5996	RGS1	NCCBC14	Human	Breast	DCIS	6.74e-04	3.22e-01	0.2021
5996	RGS1	NCCBC3	Human	Breast	DCIS	5.06e-23	7.97e-01	0.1198
5996	RGS1	NCCBC5	Human	Breast	DCIS	3.63e-19	7.47e-01	0.2046
5996	RGS1	P2	Human	Breast	IDC	9.74e-03	3.17e-01	0.21
5996	RGS1	CA_HPV_2	Human	Cervix	CC	1.09e-03	4.25e-01	0.0391
5996	RGS1	HSIL_HPV_2	Human	Cervix	HSIL_HPV	1.13e-12	-6.18e-01	0.0208
5996	RGS1	N_HPV_2	Human	Cervix	N_HPV	1.64e-03	-9.83e-02	-0.0131
5996	RGS1	CCI_1	Human	Cervix	CC	5.91e-07	-8.12e-01	0.528
5996	RGS1	CCI_2	Human	Cervix	CC	1.77e-04	-7.90e-01	0.5249
5996	RGS1	CCI_3	Human	Cervix	CC	5.26e-07	-7.81e-01	0.516
5996	RGS1	CCII_1	Human	Cervix	CC	1.50e-11	-8.01e-01	0.3249
5996	RGS1	Tumor	Human	Cervix	CC	5.89e-28	-7.98e-01	0.1241
5996	RGS1	sample1	Human	Cervix	CC	1.93e-07	-7.62e-01	0.0959
5996	RGS1	sample3	Human	Cervix	CC	3.57e-29	-7.96e-01	0.1387
5996	RGS1	H2	Human	Cervix	HSIL_HPV	1.07e-20	-7.43e-01	0.0632

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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
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
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:00430877	Cervix	CC	regulation of GTPase activity	79/2311	348/18723	4.21e-08	2.60e-06	79
GO:00435476	Cervix	CC	positive regulation of GTPase activity	53/2311	255/18723	8.72e-05	1.16e-03	53
GO:00019752	Cervix	CC	response to amphetamine	10/2311	33/18723	5.07e-03	3.00e-02	10
GO:00140754	Cervix	CC	response to amine	13/2311	49/18723	5.34e-03	3.10e-02	13
GO:1905144	Cervix	CC	response to acetylcholine	9/2311	31/18723	1.04e-02	4.97e-02	9
GO:1905145	Cervix	CC	cellular response to acetylcholine	9/2311	31/18723	1.04e-02	4.97e-02	9
GO:001407511	Cervix	HSIL_HPV	response to amine	8/737	49/18723	5.99e-04	8.37e-03	8
GO:00019751	Cervix	HSIL_HPV	response to amphetamine	6/737	33/18723	1.63e-03	1.77e-02	6
GO:00430878	Endometrium	AEH	regulation of GTPase activity	66/2100	348/18723	1.26e-05	2.77e-04	66
GO:00435477	Endometrium	AEH	positive regulation of GTPase activity	48/2100	255/18723	2.18e-04	2.67e-03	48
GO:004308712	Endometrium	EEC	regulation of GTPase activity	67/2168	348/18723	1.84e-05	3.43e-04	67
GO:004354712	Endometrium	EEC	positive regulation of GTPase activity	50/2168	255/18723	1.26e-04	1.66e-03	50
GO:0006913110	Esophagus	ESCC	nucleocytoplasmic transport	230/8552	301/18723	6.04e-28	2.02e-25	230
GO:0051169110	Esophagus	ESCC	nuclear transport	230/8552	301/18723	6.04e-28	2.02e-25	230
GO:0006979111	Esophagus	ESCC	response to oxidative stress	303/8552	446/18723	7.15e-22	1.30e-19	303
GO:000705911	Esophagus	ESCC	chromosome segregation	238/8552	346/18723	1.72e-18	1.82e-16	238
GO:000705114	Esophagus	ESCC	spindle organization	134/8552	184/18723	5.70e-14	2.87e-12	134
GO:0010563111	Esophagus	ESCC	negative regulation of phosphorus metabolic process	274/8552	442/18723	2.32e-12	9.41e-11	274
GO:0045936111	Esophagus	ESCC	negative regulation of phosphate metabolic process	273/8552	441/18723	3.18e-12	1.25e-10	273
GO:0051348111	Esophagus	ESCC	negative regulation of transferase activity	177/8552	268/18723	1.08e-11	4.00e-10	177

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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

RGS1

SNV

Missense_Mutation

novel

c.111A>C

p.Lys37Asn

p.K37N

Q08116

protein_coding

tolerated(0.19)

benign(0.402)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RGS1

SNV

Missense_Mutation

c.513N>G

p.Phe171Leu

p.F171L

Q08116

protein_coding

deleterious(0.04)

probably_damaging(0.993)

TCGA-AN-A0AL-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

RGS1

SNV

Missense_Mutation

novel

c.592N>C

p.Asn198His

p.N198H

Q08116

protein_coding

deleterious(0.03)

benign(0.053)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

RGS1

insertion

Frame_Shift_Ins

novel

c.121dupA

p.Arg41LysfsTer38

p.R41Kfs*38

Q08116

protein_coding

TCGA-CM-6162-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Chemotherapy

oxaliplatin

RGS1

SNV

Missense_Mutation

novel

c.145N>T

p.Asp49Tyr

p.D49Y

Q08116

protein_coding

deleterious(0)

probably_damaging(0.921)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

RGS1

SNV

Missense_Mutation

rs758026916

c.200N>A

p.Ser67Tyr

p.S67Y

Q08116

protein_coding

tolerated(0.37)

benign(0.007)

TCGA-AJ-A5DW-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

RGS1

SNV

Missense_Mutation

c.598C>A

p.Leu200Ile

p.L200I

Q08116

protein_coding

tolerated(0.43)

benign(0.003)

TCGA-AP-A056-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

RGS1

SNV

Missense_Mutation

c.16A>G

p.Ile6Val

p.I6V

Q08116

protein_coding

tolerated_low_confidence(0.06)

benign(0)

TCGA-B5-A11E-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

RGS1

SNV

Missense_Mutation

c.265N>T

p.Leu89Phe

p.L89F

Q08116

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-BS-A0UF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

RGS1

SNV

Missense_Mutation

novel

c.520N>T

p.Ala174Ser

p.A174S

Q08116

protein_coding

deleterious(0.03)

probably_damaging(0.999)

TCGA-EO-A22U-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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