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: SH3RF1

Gene summary for SH3RF1

Gene summary.

Gene information	Species	Human
	Gene symbol	SH3RF1
	Gene ID	57630
	Gene name	SH3 domain containing ring finger 1
	Gene Alias	POSH
	Cytomap	4q32.3-q33
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	Q7Z6J0

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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
57630	SH3RF1	GSM5252131_BPH340PrSF_Via	Human	Prostate	BPH	6.08e-17	6.15e-01	-0.2126
57630	SH3RF1	GSM5252132_BPH389PrGF	Human	Prostate	BPH	3.14e-07	7.33e-01	-0.2247
57630	SH3RF1	GSM5252133_BPH389PrSF	Human	Prostate	BPH	1.80e-04	6.59e-01	-0.2027
57630	SH3RF1	GSM5252134_BPH511PrG_Fcol_3GEX	Human	Prostate	BPH	6.20e-04	3.36e-01	-0.1433
57630	SH3RF1	GSM5252135_BPH511PrPUr_Fcol_3GEX	Human	Prostate	BPH	4.41e-10	5.31e-01	-0.1833
57630	SH3RF1	047563_1562-all-cells	Human	Prostate	BPH	2.21e-13	4.66e-01	0.0791
57630	SH3RF1	048752_1579-all-cells	Human	Prostate	BPH	1.19e-59	1.10e+00	0.1008
57630	SH3RF1	052095_1628-all-cells	Human	Prostate	BPH	4.16e-19	6.45e-01	0.1032
57630	SH3RF1	052097_1595-all-cells	Human	Prostate	BPH	7.11e-40	8.91e-01	0.0972
57630	SH3RF1	052099_1652-all-cells	Human	Prostate	BPH	2.26e-40	1.00e+00	0.1038
57630	SH3RF1	Dong_P1	Human	Prostate	Tumor	3.33e-13	4.69e-02	0.035
57630	SH3RF1	Dong_P3	Human	Prostate	Tumor	3.32e-03	-3.76e-02	0.0278
57630	SH3RF1	Dong_P4	Human	Prostate	Tumor	5.54e-03	9.77e-02	0.0292
57630	SH3RF1	Dong_P5	Human	Prostate	Tumor	4.97e-03	-9.98e-02	0.053
57630	SH3RF1	P1_S1_AK	Human	Skin	AK	4.68e-22	6.19e-01	-0.3399
57630	SH3RF1	P2_S3_AK	Human	Skin	AK	1.79e-26	6.61e-01	-0.3287
57630	SH3RF1	P2_S4_SCCIS	Human	Skin	SCCIS	7.63e-28	6.98e-01	-0.3043
57630	SH3RF1	P3_S6_AK	Human	Skin	AK	8.51e-09	3.28e-01	-0.3256
57630	SH3RF1	P4_S8_cSCC	Human	Skin	cSCC	1.37e-22	5.09e-01	-0.3095
57630	SH3RF1	P5_S10_cSCC	Human	Skin	cSCC	1.77e-14	3.51e-01	-0.299

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
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
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:200123310	Cervix	CC	regulation of apoptotic signaling pathway	96/2311	356/18723	4.08e-14	3.05e-11	96
GO:005254710	Cervix	CC	regulation of peptidase activity	112/2311	461/18723	6.70e-13	3.08e-10	112
GO:005254810	Cervix	CC	regulation of endopeptidase activity	103/2311	432/18723	1.89e-11	5.14e-09	103
GO:00421108	Cervix	CC	T cell activation	107/2311	487/18723	1.24e-09	1.46e-07	107
GO:00508638	Cervix	CC	regulation of T cell activation	80/2311	329/18723	1.28e-09	1.47e-07	80
GO:200011610	Cervix	CC	regulation of cysteine-type endopeptidase activity	61/2311	235/18723	8.69e-09	7.22e-07	61
GO:004328110	Cervix	CC	regulation of cysteine-type endopeptidase activity involved in apoptotic process	55/2311	209/18723	2.77e-08	1.95e-06	55
GO:004586110	Cervix	CC	negative regulation of proteolysis	80/2311	351/18723	2.88e-08	1.98e-06	80
GO:200123410	Cervix	CC	negative regulation of apoptotic signaling pathway	56/2311	224/18723	1.39e-07	6.70e-06	56
GO:190370610	Cervix	CC	regulation of hemopoiesis	80/2311	367/18723	2.14e-07	9.55e-06	80
GO:00513469	Cervix	CC	negative regulation of hydrolase activity	81/2311	379/18723	4.27e-07	1.67e-05	81
GO:00310988	Cervix	CC	stress-activated protein kinase signaling cascade	58/2311	247/18723	8.02e-07	2.89e-05	58
GO:00104669	Cervix	CC	negative regulation of peptidase activity	60/2311	262/18723	1.27e-06	4.34e-05	60
GO:00420988	Cervix	CC	T cell proliferation	49/2311	199/18723	1.32e-06	4.49e-05	49
GO:009719110	Cervix	CC	extrinsic apoptotic signaling pathway	52/2311	219/18723	2.06e-06	6.34e-05	52
GO:00514038	Cervix	CC	stress-activated MAPK cascade	55/2311	239/18723	2.96e-06	8.31e-05	55
GO:00421297	Cervix	CC	regulation of T cell proliferation	43/2311	171/18723	3.21e-06	8.77e-05	43
GO:19021056	Cervix	CC	regulation of leukocyte differentiation	61/2311	279/18723	5.16e-06	1.29e-04	61
GO:00706637	Cervix	CC	regulation of leukocyte proliferation	55/2311	245/18723	6.51e-06	1.56e-04	55
GO:001095110	Cervix	CC	negative regulation of endopeptidase activity	56/2311	252/18723	7.43e-06	1.74e-04	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

SH3RF1

SNV

Missense_Mutation

novel

c.2350N>T

p.Ala784Ser

p.A784S

Q7Z6J0

protein_coding

tolerated(1)

benign(0)

TCGA-A8-A07W-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

exemestane

SH3RF1

SNV

Missense_Mutation

novel

c.2125N>C

p.Asp709His

p.D709H

Q7Z6J0

protein_coding

deleterious(0.01)

probably_damaging(0.997)

TCGA-AC-A5EH-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SH3RF1

SNV

Missense_Mutation

novel

c.1762N>G

p.Asn588Asp

p.N588D

Q7Z6J0

protein_coding

tolerated(0.06)

benign(0.112)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

SH3RF1

SNV

Missense_Mutation

c.1033G>A

p.Glu345Lys

p.E345K

Q7Z6J0

protein_coding

deleterious(0.01)

probably_damaging(0.94)

TCGA-AR-A250-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

SH3RF1

SNV

Missense_Mutation

novel

c.1129N>A

p.Gly377Ser

p.G377S

Q7Z6J0

protein_coding

tolerated(0.11)

possibly_damaging(0.661)

TCGA-D8-A73U-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

SH3RF1

insertion

Frame_Shift_Ins

novel

c.411_412insGCCCACCTGGTGTCCTTTCCAAC

p.Cys138AlafsTer80

p.C138Afs*80

Q7Z6J0

protein_coding

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

SH3RF1

insertion

Nonsense_Mutation

novel

c.2194_2195insGTTCCAGGAAAAAACTAAAAAATGAACAATAG

p.Pro732ArgfsTer11

p.P732Rfs*11

Q7Z6J0

protein_coding

TCGA-BH-A0B1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

adriamycin

SH3RF1

SNV

Missense_Mutation

novel

c.1726N>T

p.His576Tyr

p.H576Y

Q7Z6J0

protein_coding

deleterious(0.01)

benign(0.172)

TCGA-EA-A3HS-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SH3RF1

SNV

Missense_Mutation

novel

c.578C>T

p.Pro193Leu

p.P193L

Q7Z6J0

protein_coding

deleterious(0)

benign(0.158)

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SH3RF1

SNV

Missense_Mutation

rs755524119

c.1569N>C

p.Gln523His

p.Q523H

Q7Z6J0

protein_coding

tolerated(0.15)

possibly_damaging(0.556)

TCGA-EK-A3GJ-01

Cervix

cervical & endocervical cancer

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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