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: RNF11

Gene summary for RNF11

Gene summary.

Gene information	Species	Human
	Gene symbol	RNF11
	Gene ID	26994
	Gene name	ring finger protein 11
	Gene Alias	CGI-123
	Cytomap	1p32.3
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	Q9Y3C5

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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
26994	RNF11	LZE4T	Human	Esophagus	ESCC	1.38e-07	5.51e-02	0.0811
26994	RNF11	LZE5T	Human	Esophagus	ESCC	1.41e-02	1.85e-01	0.0514
26994	RNF11	LZE7T	Human	Esophagus	ESCC	5.24e-05	-9.32e-02	0.0667
26994	RNF11	LZE8T	Human	Esophagus	ESCC	1.27e-03	-2.21e-01	0.067
26994	RNF11	LZE22D1	Human	Esophagus	HGIN	1.52e-04	-5.07e-02	0.0595
26994	RNF11	LZE24T	Human	Esophagus	ESCC	8.02e-18	8.69e-01	0.0596
26994	RNF11	P2T-E	Human	Esophagus	ESCC	5.76e-47	8.60e-01	0.1177
26994	RNF11	P4T-E	Human	Esophagus	ESCC	4.10e-11	3.69e-01	0.1323
26994	RNF11	P5T-E	Human	Esophagus	ESCC	5.55e-17	3.19e-01	0.1327
26994	RNF11	P8T-E	Human	Esophagus	ESCC	5.82e-22	4.94e-01	0.0889
26994	RNF11	P9T-E	Human	Esophagus	ESCC	5.69e-11	2.40e-01	0.1131
26994	RNF11	P10T-E	Human	Esophagus	ESCC	7.88e-35	7.65e-01	0.116
26994	RNF11	P11T-E	Human	Esophagus	ESCC	3.26e-07	5.97e-01	0.1426
26994	RNF11	P12T-E	Human	Esophagus	ESCC	7.01e-20	5.93e-01	0.1122
26994	RNF11	P15T-E	Human	Esophagus	ESCC	1.07e-21	6.80e-01	0.1149
26994	RNF11	P16T-E	Human	Esophagus	ESCC	3.34e-18	2.01e-01	0.1153
26994	RNF11	P17T-E	Human	Esophagus	ESCC	7.30e-07	6.32e-01	0.1278
26994	RNF11	P19T-E	Human	Esophagus	ESCC	7.13e-08	1.04e+00	0.1662
26994	RNF11	P20T-E	Human	Esophagus	ESCC	1.60e-20	7.24e-01	0.1124
26994	RNF11	P21T-E	Human	Esophagus	ESCC	1.87e-36	8.32e-01	0.1617

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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: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:00071738	Cervix	CC	epidermal growth factor receptor signaling pathway	36/2311	108/18723	1.04e-08	8.44e-07	36
GO:00381278	Cervix	CC	ERBB signaling pathway	37/2311	121/18723	8.57e-08	4.88e-06	37
GO:00002097	Cervix	CC	protein polyubiquitination	58/2311	236/18723	1.57e-07	7.41e-06	58
GO:00709366	Cervix	CC	protein K48-linked ubiquitination	22/2311	65/18723	5.56e-06	1.38e-04	22
GO:00420586	Cervix	CC	regulation of epidermal growth factor receptor signaling pathway	21/2311	73/18723	1.36e-04	1.67e-03	21
GO:19011846	Cervix	CC	regulation of ERBB signaling pathway	22/2311	79/18723	1.61e-04	1.93e-03	22
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:19011857	Cervix	CC	negative regulation of ERBB signaling pathway	10/2311	32/18723	3.96e-03	2.48e-02	10
GO:00420597	Cervix	CC	negative regulation of epidermal growth factor receptor signaling pathway	9/2311	28/18723	5.02e-03	2.98e-02	9
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:00518656	Cervix	CC	protein autoubiquitination	17/2311	73/18723	6.71e-03	3.70e-02	17
GO:00705343	Cervix	CC	protein K63-linked ubiquitination	14/2311	56/18723	6.93e-03	3.74e-02	14
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

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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

RNF11

insertion

Nonsense_Mutation

novel

c.228_229insTACTCAGGAGGCTGAGGTTGGAGGATTGCTTGAGCCCAGGGGGTTG

p.Ile77TyrfsTer5

p.I77Yfs*5

Q9Y3C5

protein_coding

TCGA-A8-A07J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

RNF11

SNV

Missense_Mutation

c.218N>T

p.Arg73Ile

p.R73I

Q9Y3C5

protein_coding

deleterious(0.01)

possibly_damaging(0.496)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

RNF11

SNV

Missense_Mutation

rs866084029

c.346C>T

p.Pro116Ser

p.P116S

Q9Y3C5

protein_coding

deleterious(0)

probably_damaging(0.984)

TCGA-G4-6304-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Chemotherapy

fluorouracil

RNF11

SNV

Missense_Mutation

novel

c.372C>A

p.Asp124Glu

p.D124E

Q9Y3C5

protein_coding

tolerated(0.52)

benign(0.012)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

RNF11

SNV

Missense_Mutation

c.218N>T

p.Arg73Ile

p.R73I

Q9Y3C5

protein_coding

deleterious(0.01)

possibly_damaging(0.496)

TCGA-BS-A0UV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

RNF11

insertion

Frame_Shift_Ins

novel

c.455_456insGAATTTGCAG

p.Thr153AsnfsTer5

p.T153Nfs*5

Q9Y3C5

protein_coding

TCGA-BS-A0UJ-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

RNF11

SNV

Missense_Mutation

c.40N>A

p.Ser14Thr

p.S14T

Q9Y3C5

protein_coding

tolerated(0.17)

possibly_damaging(0.715)

TCGA-DD-A4NH-01

Liver

liver hepatocellular carcinoma

Female

>=65

III/IV

Targeted Molecular therapy

sorafenib

RNF11

SNV

Missense_Mutation

c.285N>T

p.Lys95Asn

p.K95N

Q9Y3C5

protein_coding

deleterious(0.02)

benign(0.254)

TCGA-91-A4BC-01

Lung

lung adenocarcinoma

Male

<65

I/II

Unknown

RNF11

SNV

Missense_Mutation

novel

c.162C>G

p.Ser54Arg

p.S54R

Q9Y3C5

protein_coding

tolerated(0.12)

benign(0.255)

TCGA-22-5481-01

Lung

lung squamous cell carcinoma

Female

>=65

I/II

Unknown

RNF11

SNV

Missense_Mutation

novel

c.124G>C

p.Glu42Gln

p.E42Q

Q9Y3C5

protein_coding

tolerated(0.12)

benign(0.01)

TCGA-CV-7242-01

Oral cavity

head & neck squamous cell 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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