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: RNF111

Gene summary for RNF111

Gene summary.

Gene information	Species	Human
	Gene symbol	RNF111
	Gene ID	54778
	Gene name	ring finger protein 111
	Gene Alias	ARK
	Cytomap	15q22.1-q22.2
	Gene Type	protein-coding
	GO ID	GO:0000209
	UniProtAcc	Q6ZNA4

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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
54778	RNF111	CCI_1	Human	Cervix	CC	5.66e-09	9.51e-01	0.528
54778	RNF111	CCI_2	Human	Cervix	CC	1.22e-14	1.34e+00	0.5249
54778	RNF111	CCI_3	Human	Cervix	CC	2.41e-14	8.78e-01	0.516
54778	RNF111	HTA11_3410_2000001011	Human	Colorectum	AD	6.20e-14	-5.38e-01	0.0155
54778	RNF111	HTA11_2487_2000001011	Human	Colorectum	SER	7.69e-04	-4.26e-01	-0.1808
54778	RNF111	HTA11_3361_2000001011	Human	Colorectum	AD	1.53e-05	-5.46e-01	-0.1207
54778	RNF111	HTA11_696_2000001011	Human	Colorectum	AD	1.60e-04	-3.31e-01	-0.1464
54778	RNF111	HTA11_866_2000001011	Human	Colorectum	AD	4.60e-04	-3.28e-01	-0.1001
54778	RNF111	HTA11_866_3004761011	Human	Colorectum	AD	1.20e-06	-4.71e-01	0.096
54778	RNF111	HTA11_10711_2000001011	Human	Colorectum	AD	4.72e-04	-4.77e-01	0.0338
54778	RNF111	HTA11_7696_3000711011	Human	Colorectum	AD	1.41e-13	-4.64e-01	0.0674
54778	RNF111	HTA11_99999970781_79442	Human	Colorectum	MSS	2.66e-09	-4.32e-01	0.294
54778	RNF111	HTA11_99999971662_82457	Human	Colorectum	MSS	6.04e-18	-5.01e-01	0.3859
54778	RNF111	HTA11_99999973899_84307	Human	Colorectum	MSS	5.86e-04	-5.42e-01	0.2585
54778	RNF111	HTA11_99999974143_84620	Human	Colorectum	MSS	4.29e-16	-5.09e-01	0.3005
54778	RNF111	F007	Human	Colorectum	FAP	3.17e-03	-3.34e-01	0.1176
54778	RNF111	A001-C-207	Human	Colorectum	FAP	1.95e-07	-3.73e-01	0.1278
54778	RNF111	A015-C-203	Human	Colorectum	FAP	2.52e-30	-4.90e-01	-0.1294
54778	RNF111	A015-C-204	Human	Colorectum	FAP	7.46e-12	-5.00e-01	-0.0228
54778	RNF111	A014-C-040	Human	Colorectum	FAP	2.36e-07	-5.74e-01	-0.1184

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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

∗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:190332010	Cervix	CC	regulation of protein modification by small protein conjugation or removal	66/2311	242/18723	2.31e-10	3.46e-08	66
GO:003139610	Cervix	CC	regulation of protein ubiquitination	59/2311	210/18723	5.90e-10	7.51e-08	59
GO:00002097	Cervix	CC	protein polyubiquitination	58/2311	236/18723	1.57e-07	7.41e-06	58
GO:00071786	Cervix	CC	transmembrane receptor protein serine/threonine kinase signaling pathway	67/2311	355/18723	2.39e-04	2.67e-03	67
GO:00715595	Cervix	CC	response to transforming growth factor beta	50/2311	256/18723	6.31e-04	5.91e-03	50
GO:00715605	Cervix	CC	cellular response to transforming growth factor beta stimulus	49/2311	250/18723	6.55e-04	6.05e-03	49
GO:00071795	Cervix	CC	transforming growth factor beta receptor signaling pathway	38/2311	198/18723	3.62e-03	2.31e-02	38
GO:00313983	Cervix	CC	positive regulation of protein ubiquitination	25/2311	119/18723	5.09e-03	3.01e-02	25
GO:19033224	Cervix	CC	positive regulation of protein modification by small protein conjugation or removal	28/2311	138/18723	5.26e-03	3.08e-02	28
GO:1903320	Colorectum	AD	regulation of protein modification by small protein conjugation or removal	86/3918	242/18723	9.43e-08	4.65e-06	86
GO:0031396	Colorectum	AD	regulation of protein ubiquitination	72/3918	210/18723	4.50e-06	1.21e-04	72
GO:0000209	Colorectum	AD	protein polyubiquitination	78/3918	236/18723	8.71e-06	2.06e-04	78
GO:0007178	Colorectum	AD	transmembrane receptor protein serine/threonine kinase signaling pathway	99/3918	355/18723	9.92e-04	9.28e-03	99
GO:0071559	Colorectum	AD	response to transforming growth factor beta	74/3918	256/18723	1.45e-03	1.23e-02	74
GO:0071560	Colorectum	AD	cellular response to transforming growth factor beta stimulus	72/3918	250/18723	1.85e-03	1.52e-02	72
GO:0007179	Colorectum	AD	transforming growth factor beta receptor signaling pathway	59/3918	198/18723	1.94e-03	1.58e-02	59
GO:19033201	Colorectum	SER	regulation of protein modification by small protein conjugation or removal	70/2897	242/18723	6.84e-08	4.42e-06	70
GO:00313961	Colorectum	SER	regulation of protein ubiquitination	62/2897	210/18723	1.69e-07	9.71e-06	62
GO:00002091	Colorectum	SER	protein polyubiquitination	58/2897	236/18723	1.69e-04	3.18e-03	58
GO:1903322	Colorectum	SER	positive regulation of protein modification by small protein conjugation or removal	34/2897	138/18723	3.30e-03	2.83e-02	34

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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

RNF111

SNV

Missense_Mutation

novel

c.1027N>T

p.His343Tyr

p.H343Y

Q6ZNA4

protein_coding

deleterious(0.01)

possibly_damaging(0.805)

TCGA-AC-A2BK-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cytoxan

RNF111

SNV

Missense_Mutation

novel

c.711G>T

p.Lys237Asn

p.K237N

Q6ZNA4

protein_coding

deleterious(0.04)

probably_damaging(0.997)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RNF111

SNV

Missense_Mutation

rs762937096

c.1793G>A

p.Arg598Gln

p.R598Q

Q6ZNA4

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.997)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RNF111

SNV

Missense_Mutation

c.128T>A

p.Ile43Asn

p.I43N

Q6ZNA4

protein_coding

deleterious_low_confidence(0)

benign(0.44)

TCGA-E9-A243-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

RNF111

SNV

Missense_Mutation

rs779507691

c.2495C>T

p.Pro832Leu

p.P832L

Q6ZNA4

protein_coding

deleterious(0.04)

benign(0.225)

TCGA-E9-A3HO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

RNF111

deletion

Frame_Shift_Del

c.2863_2866delTTGT

p.Ser956PhefsTer2

p.S956Ffs*2

Q6ZNA4

protein_coding

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RNF111

deletion

Frame_Shift_Del

c.1911_1914delNNNN

p.Leu639HisfsTer14

p.L639Hfs*14

Q6ZNA4

protein_coding

TCGA-AO-A0J3-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cyclophosphamide

RNF111

insertion

Frame_Shift_Ins

novel

c.2173_2174insCTTTTTTTGGTGGAGACGAGGT

p.Pro726PhefsTer31

p.P726Ffs*31

Q6ZNA4

protein_coding

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

RNF111

SNV

Missense_Mutation

novel

c.2140N>T

p.Ala714Ser

p.A714S

Q6ZNA4

protein_coding

tolerated(0.41)

benign(0)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RNF111

SNV

Missense_Mutation

novel

c.2836N>A

p.Asp946Asn

p.D946N

Q6ZNA4

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-2W-A8YY-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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