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: RNF10

Gene summary for RNF10

Gene summary.

Gene information	Species	Human
	Gene symbol	RNF10
	Gene ID	9921
	Gene name	ring finger protein 10
	Gene Alias	RIE2
	Cytomap	12q24.31
	Gene Type	protein-coding
	GO ID	GO:0003008
	UniProtAcc	Q8N5U6

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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
9921	RNF10	HTA11_347_2000001011	Human	Colorectum	AD	2.13e-02	3.57e-01	-0.1954
9921	RNF10	HTA11_696_2000001011	Human	Colorectum	AD	5.29e-03	3.57e-01	-0.1464
9921	RNF10	HTA11_1391_2000001011	Human	Colorectum	AD	9.24e-03	5.07e-01	-0.059
9921	RNF10	HTA11_99999971662_82457	Human	Colorectum	MSS	4.12e-02	4.44e-01	0.3859
9921	RNF10	A015-C-203	Human	Colorectum	FAP	1.37e-15	-2.62e-01	-0.1294
9921	RNF10	A014-C-040	Human	Colorectum	FAP	4.05e-02	-3.35e-01	-0.1184
9921	RNF10	A002-C-201	Human	Colorectum	FAP	3.29e-09	-2.15e-01	0.0324
9921	RNF10	A001-C-108	Human	Colorectum	FAP	1.67e-09	-1.74e-01	-0.0272
9921	RNF10	A002-C-205	Human	Colorectum	FAP	2.51e-11	-2.16e-01	-0.1236
9921	RNF10	A015-C-005	Human	Colorectum	FAP	2.82e-03	-2.23e-01	-0.0336
9921	RNF10	A015-C-006	Human	Colorectum	FAP	7.14e-10	-2.83e-01	-0.0994
9921	RNF10	A015-C-106	Human	Colorectum	FAP	2.93e-08	-2.04e-01	-0.0511
9921	RNF10	A002-C-114	Human	Colorectum	FAP	1.14e-10	-2.50e-01	-0.1561
9921	RNF10	A015-C-104	Human	Colorectum	FAP	2.64e-14	-2.17e-01	-0.1899
9921	RNF10	A001-C-014	Human	Colorectum	FAP	8.64e-06	-1.55e-01	0.0135
9921	RNF10	A002-C-016	Human	Colorectum	FAP	1.71e-11	-2.30e-01	0.0521
9921	RNF10	A015-C-002	Human	Colorectum	FAP	2.75e-06	-2.58e-01	-0.0763
9921	RNF10	A001-C-203	Human	Colorectum	FAP	3.40e-05	-1.16e-01	-0.0481
9921	RNF10	A002-C-116	Human	Colorectum	FAP	1.27e-15	-2.36e-01	-0.0452
9921	RNF10	A014-C-008	Human	Colorectum	FAP	1.02e-07	-2.37e-01	-0.191

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0051865	Colorectum	AD	protein autoubiquitination	28/3918	73/18723	4.87e-04	5.30e-03	28
GO:0050767	Colorectum	AD	regulation of neurogenesis	99/3918	364/18723	2.35e-03	1.82e-02	99
GO:00507671	Colorectum	MSS	regulation of neurogenesis	94/3467	364/18723	3.12e-04	4.06e-03	94
GO:00518651	Colorectum	MSS	protein autoubiquitination	25/3467	73/18723	1.00e-03	1.00e-02	25
GO:0050768	Colorectum	MSS	negative regulation of neurogenesis	39/3467	140/18723	4.30e-03	3.07e-02	39
GO:0051961	Colorectum	MSS	negative regulation of nervous system development	40/3467	145/18723	4.66e-03	3.27e-02	40
GO:0051960	Colorectum	MSS	regulation of nervous system development	103/3467	443/18723	6.68e-03	4.38e-02	103
GO:00507672	Colorectum	FAP	regulation of neurogenesis	82/2622	364/18723	6.28e-06	1.96e-04	82
GO:00519601	Colorectum	FAP	regulation of nervous system development	89/2622	443/18723	2.32e-04	3.25e-03	89
GO:00518652	Colorectum	FAP	protein autoubiquitination	22/2622	73/18723	2.88e-04	3.77e-03	22
GO:00507681	Colorectum	FAP	negative regulation of neurogenesis	32/2622	140/18723	3.08e-03	2.32e-02	32
GO:0010721	Colorectum	FAP	negative regulation of cell development	39/2622	180/18723	3.25e-03	2.40e-02	39
GO:00519611	Colorectum	FAP	negative regulation of nervous system development	32/2622	145/18723	5.41e-03	3.53e-02	32
GO:00507673	Colorectum	CRC	regulation of neurogenesis	68/2078	364/18723	1.11e-05	3.62e-04	68
GO:00518653	Colorectum	CRC	protein autoubiquitination	18/2078	73/18723	8.33e-04	1.04e-02	18
GO:00519602	Colorectum	CRC	regulation of nervous system development	71/2078	443/18723	9.28e-04	1.14e-02	71
GO:00107211	Colorectum	CRC	negative regulation of cell development	34/2078	180/18723	1.33e-03	1.49e-02	34
GO:00519612	Colorectum	CRC	negative regulation of nervous system development	28/2078	145/18723	2.43e-03	2.30e-02	28
GO:00507682	Colorectum	CRC	negative regulation of neurogenesis	27/2078	140/18723	2.92e-03	2.64e-02	27
GO:00507677	Endometrium	AEH	regulation of neurogenesis	56/2100	364/18723	8.87e-03	4.82e-02	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

RNF10

SNV

Missense_Mutation

novel

c.2261N>G

p.Glu754Gly

p.E754G

Q8N5U6

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A8-A06Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RNF10

SNV

Missense_Mutation

novel

c.1776N>T

p.Lys592Asn

p.K592N

Q8N5U6

protein_coding

deleterious(0.02)

possibly_damaging(0.756)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RNF10

SNV

Missense_Mutation

novel

c.1132N>T

p.Arg378Trp

p.R378W

Q8N5U6

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-AR-A1AY-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unspecific

Doxorubicin

RNF10

SNV

Missense_Mutation

rs767518780

c.1694N>A

p.Arg565His

p.R565H

Q8N5U6

protein_coding

deleterious(0)

possibly_damaging(0.907)

TCGA-B6-A0I9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

RNF10

SNV

Missense_Mutation

c.1145T>A

p.Leu382Gln

p.L382Q

Q8N5U6

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-BH-A0H7-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

RNF10

SNV

Missense_Mutation

novel

c.1613N>T

p.Ser538Ile

p.S538I

Q8N5U6

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-C8-A26X-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

RNF10

SNV

Missense_Mutation

c.1549N>A

p.Glu517Lys

p.E517K

Q8N5U6

protein_coding

deleterious(0.02)

possibly_damaging(0.802)

TCGA-D8-A1JP-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

RNF10

SNV

Missense_Mutation

rs779356543

c.1861N>T

p.Arg621Cys

p.R621C

Q8N5U6

protein_coding

deleterious(0)

benign(0.177)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RNF10

SNV

Missense_Mutation

rs141915839

c.304N>A

p.Gly102Ser

p.G102S

Q8N5U6

protein_coding

tolerated_low_confidence(0.17)

benign(0.087)

TCGA-EA-A3HS-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

RNF10

SNV

Missense_Mutation

c.1243N>G

p.Gln415Glu

p.Q415E

Q8N5U6

protein_coding

tolerated(1)

benign(0.079)

TCGA-IR-A3LH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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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