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: RXFP1

Gene summary for RXFP1

Gene summary.

Gene information	Species	Human
	Gene symbol	RXFP1
	Gene ID	59350
	Gene name	relaxin family peptide receptor 1
	Gene Alias	LGR7
	Cytomap	4q32.1
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	B4DGP2

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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
59350	RXFP1	AEH-subject1	Human	Endometrium	AEH	2.25e-09	4.69e-01	-0.3059
59350	RXFP1	AEH-subject5	Human	Endometrium	AEH	1.26e-27	8.11e-01	-0.2953
59350	RXFP1	GSM5276937	Human	Endometrium	EEC	1.17e-04	-1.64e-01	-0.0897
59350	RXFP1	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	1.24e-02	-1.44e-01	-0.1869
59350	RXFP1	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	1.21e-04	-1.50e-01	-0.1934
59350	RXFP1	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	1.50e-03	-1.32e-01	-0.1917
59350	RXFP1	GSM6177622_NYU_UCEC3_lib2_lib2	Human	Endometrium	EEC	1.51e-03	-1.28e-01	-0.1916

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Endometrium		AEH: Atypical endometrial hyperplasia
Endometrium		EEC: Endometrioid 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:004873216	Endometrium	AEH	gland development	83/2100	436/18723	8.62e-07	3.11e-05	83
GO:00447065	Endometrium	AEH	multi-multicellular organism process	45/2100	220/18723	4.55e-05	7.61e-04	45
GO:00097558	Endometrium	AEH	hormone-mediated signaling pathway	37/2100	190/18723	5.64e-04	5.62e-03	37
GO:0061448	Endometrium	AEH	connective tissue development	44/2100	252/18723	1.92e-03	1.51e-02	44
GO:00605414	Endometrium	AEH	respiratory system development	37/2100	203/18723	1.97e-03	1.54e-02	37
GO:00303246	Endometrium	AEH	lung development	33/2100	177/18723	2.30e-03	1.74e-02	33
GO:00303236	Endometrium	AEH	respiratory tube development	33/2100	181/18723	3.33e-03	2.32e-02	33
GO:00308798	Endometrium	AEH	mammary gland development	26/2100	137/18723	4.97e-03	3.13e-02	26
GO:004873217	Endometrium	EEC	gland development	83/2168	436/18723	3.08e-06	8.48e-05	83
GO:004470612	Endometrium	EEC	multi-multicellular organism process	45/2168	220/18723	9.73e-05	1.35e-03	45
GO:000975513	Endometrium	EEC	hormone-mediated signaling pathway	38/2168	190/18723	5.18e-04	5.21e-03	38
GO:00614481	Endometrium	EEC	connective tissue development	44/2168	252/18723	3.51e-03	2.36e-02	44
GO:006054112	Endometrium	EEC	respiratory system development	36/2168	203/18723	6.02e-03	3.57e-02	36
GO:003032414	Endometrium	EEC	lung development	32/2168	177/18723	6.93e-03	3.98e-02	32
GO:003087912	Endometrium	EEC	mammary gland development	26/2168	137/18723	7.50e-03	4.20e-02	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

RXFP1

SNV

Missense_Mutation

c.844G>A

p.Glu282Lys

p.E282K

protein_coding

deleterious(0)

probably_damaging(0.944)

TCGA-A2-A0YH-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

RXFP1

SNV

Missense_Mutation

c.1336N>G

p.Thr446Ala

p.T446A

protein_coding

deleterious(0)

possibly_damaging(0.873)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RXFP1

SNV

Missense_Mutation

rs370806249

c.2295N>G

p.Phe765Leu

p.F765L

protein_coding

tolerated_low_confidence(0.13)

benign(0.003)

TCGA-AN-A0XN-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

RXFP1

insertion

Nonsense_Mutation

novel

c.726_727insTAATTAATTAATCAATCTATTCATTCAT

p.Pro243Ter

p.P243*

protein_coding

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RXFP1

insertion

Frame_Shift_Ins

novel

c.120_121insCTCCTACCTCCCCTACTCTCATGGGTGA

p.Pro42LeufsTer16

p.P42Lfs*16

protein_coding

TCGA-BH-A0BD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

RXFP1

SNV

Missense_Mutation

c.1637G>C

p.Arg546Thr

p.R546T

protein_coding

deleterious(0.03)

possibly_damaging(0.506)

TCGA-C5-A7CJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RXFP1

SNV

Missense_Mutation

c.2272N>A

p.Glu758Lys

p.E758K

protein_coding

tolerated_low_confidence(0.32)

benign(0.001)

TCGA-EK-A2PG-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

RXFP1

SNV

Missense_Mutation

c.1901N>G

p.His634Arg

p.H634R

protein_coding

tolerated(0.29)

benign(0.085)

TCGA-A6-3809-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

RXFP1

SNV

Missense_Mutation

rs771654308

c.482A>T

p.Gln161Leu

p.Q161L

protein_coding

deleterious(0.01)

benign(0.41)

TCGA-AA-3842-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

folinic

RXFP1

SNV

Missense_Mutation

novel

c.2300A>G

p.Tyr767Cys

p.Y767C

protein_coding

deleterious_low_confidence(0)

benign(0.312)

TCGA-AA-A00Z-01

Colorectum

colon adenocarcinoma

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
59350	RXFP1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME, KINASE	agonist	135652435	RELAXIN
59350	RXFP1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME, KINASE	antagonist	178101185
59350	RXFP1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME, KINASE		GNF-PF-574	CHEMBL582737
59350	RXFP1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME, KINASE	agonist	135652434	RELAXIN
59350	RXFP1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME, KINASE		COLFORSIN	COLFORSIN
59350	RXFP1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME, KINASE		2-CHLOROADENOSINE	CHEMBL285819
59350	RXFP1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME, KINASE		NSC-675972	CHEMBL1379243
59350	RXFP1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME, KINASE		DNDI1416917	CHEMBL1335833
59350	RXFP1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME, KINASE		IB-MECA	IB-MECA
59350	RXFP1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME, KINASE	agonist	135651880	RELAXIN

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