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: RNF217

Gene summary for RNF217

Gene summary.

Gene information	Species	Human
	Gene symbol	RNF217
	Gene ID	154214
	Gene name	ring finger protein 217
	Gene Alias	C6orf172
	Cytomap	6q22.31
	Gene Type	protein-coding
	GO ID	GO:0000209
	UniProtAcc	B3KVC8

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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
154214	RNF217	CCI_1	Human	Cervix	CC	1.90e-08	9.04e-01	0.528
154214	RNF217	CCI_2	Human	Cervix	CC	5.98e-10	1.31e+00	0.5249
154214	RNF217	CCI_3	Human	Cervix	CC	2.29e-08	8.47e-01	0.516
154214	RNF217	sample3	Human	Cervix	CC	2.24e-05	2.41e-01	0.1387
154214	RNF217	T3	Human	Cervix	CC	2.00e-05	2.48e-01	0.1389
154214	RNF217	LZE4T	Human	Esophagus	ESCC	9.15e-19	7.18e-01	0.0811
154214	RNF217	LZE7T	Human	Esophagus	ESCC	8.26e-06	3.41e-01	0.0667
154214	RNF217	LZE20T	Human	Esophagus	ESCC	5.09e-03	4.77e-02	0.0662
154214	RNF217	LZE24T	Human	Esophagus	ESCC	4.88e-04	5.12e-02	0.0596
154214	RNF217	LZE21T	Human	Esophagus	ESCC	4.17e-02	1.71e-01	0.0655
154214	RNF217	P2T-E	Human	Esophagus	ESCC	5.14e-11	6.89e-02	0.1177
154214	RNF217	P4T-E	Human	Esophagus	ESCC	5.63e-12	1.49e-01	0.1323
154214	RNF217	P5T-E	Human	Esophagus	ESCC	1.08e-10	1.32e-01	0.1327
154214	RNF217	P8T-E	Human	Esophagus	ESCC	1.73e-08	7.36e-02	0.0889
154214	RNF217	P9T-E	Human	Esophagus	ESCC	1.04e-04	1.72e-01	0.1131
154214	RNF217	P10T-E	Human	Esophagus	ESCC	6.99e-10	1.70e-01	0.116
154214	RNF217	P11T-E	Human	Esophagus	ESCC	1.13e-06	1.75e-01	0.1426
154214	RNF217	P12T-E	Human	Esophagus	ESCC	1.05e-13	1.54e-01	0.1122
154214	RNF217	P15T-E	Human	Esophagus	ESCC	1.05e-12	3.61e-01	0.1149
154214	RNF217	P16T-E	Human	Esophagus	ESCC	9.04e-03	2.68e-03	0.1153

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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
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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
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:004217610	Cervix	CC	regulation of protein catabolic process	104/2311	391/18723	9.39e-15	9.36e-12	104
GO:004586210	Cervix	CC	positive regulation of proteolysis	95/2311	372/18723	1.84e-12	6.86e-10	95
GO:190336210	Cervix	CC	regulation of cellular protein catabolic process	72/2311	255/18723	5.98e-12	2.10e-09	72
GO:004573210	Cervix	CC	positive regulation of protein catabolic process	65/2311	231/18723	7.44e-11	1.39e-08	65
GO:001049810	Cervix	CC	proteasomal protein catabolic process	111/2311	490/18723	8.98e-11	1.58e-08	111
GO:000989610	Cervix	CC	positive regulation of catabolic process	109/2311	492/18723	5.26e-10	6.99e-08	109
GO:190305010	Cervix	CC	regulation of proteolysis involved in cellular protein catabolic process	60/2311	221/18723	1.82e-09	1.98e-07	60
GO:200005810	Cervix	CC	regulation of ubiquitin-dependent protein catabolic process	47/2311	164/18723	1.63e-08	1.25e-06	47
GO:004316110	Cervix	CC	proteasome-mediated ubiquitin-dependent protein catabolic process	91/2311	412/18723	1.65e-08	1.25e-06	91
GO:003133110	Cervix	CC	positive regulation of cellular catabolic process	91/2311	427/18723	9.64e-08	5.25e-06	91
GO:00002097	Cervix	CC	protein polyubiquitination	58/2311	236/18723	1.57e-07	7.41e-06	58
GO:190336410	Cervix	CC	positive regulation of cellular protein catabolic process	43/2311	155/18723	1.80e-07	8.28e-06	43
GO:006113610	Cervix	CC	regulation of proteasomal protein catabolic process	48/2311	187/18723	4.63e-07	1.77e-05	48
GO:003243410	Cervix	CC	regulation of proteasomal ubiquitin-dependent protein catabolic process	38/2311	134/18723	4.99e-07	1.88e-05	38
GO:19030528	Cervix	CC	positive regulation of proteolysis involved in cellular protein catabolic process	34/2311	133/18723	2.28e-05	4.01e-04	34
GO:200006010	Cervix	CC	positive regulation of ubiquitin-dependent protein catabolic process	29/2311	107/18723	2.77e-05	4.62e-04	29
GO:00324369	Cervix	CC	positive regulation of proteasomal ubiquitin-dependent protein catabolic process	25/2311	90/18723	6.22e-05	8.90e-04	25
GO:19018008	Cervix	CC	positive regulation of proteasomal protein catabolic process	29/2311	114/18723	9.71e-05	1.27e-03	29
GO:0010498111	Esophagus	ESCC	proteasomal protein catabolic process	369/8552	490/18723	1.13e-41	1.80e-38	369
GO:0043161111	Esophagus	ESCC	proteasome-mediated ubiquitin-dependent protein catabolic process	312/8552	412/18723	3.53e-36	4.48e-33	312

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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

RNF217

SNV

Missense_Mutation

rs865840139

c.943G>A

p.Glu315Lys

p.E315K

Q8TC41

protein_coding

tolerated(0.07)

probably_damaging(0.999)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RNF217

insertion

Frame_Shift_Ins

novel

c.1240_1241insGATGCAGTGTTGATGTCTGTATGTGTTTGCGTAAGGCC

p.Glu414GlyfsTer39

p.E414Gfs*39

Q8TC41

protein_coding

TCGA-B6-A0I6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

RNF217

deletion

Frame_Shift_Del

novel

c.1623delN

p.Trp542GlyfsTer10

p.W542Gfs*10

Q8TC41

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

RNF217

SNV

Missense_Mutation

novel

c.346G>A

p.Asp116Asn

p.D116N

Q8TC41

protein_coding

deleterious_low_confidence(0.02)

benign(0.078)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RNF217

SNV

Missense_Mutation

c.1277N>A

p.Cys426Tyr

p.C426Y

Q8TC41

protein_coding

deleterious(0.04)

probably_damaging(0.924)

TCGA-JW-A5VJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

RNF217

SNV

Missense_Mutation

novel

c.601N>G

p.Arg201Gly

p.R201G

Q8TC41

protein_coding

tolerated_low_confidence(0.35)

benign(0.03)

TCGA-VS-A953-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

RNF217

insertion

Frame_Shift_Ins

novel

c.1587_1588insA

p.Gln532ThrfsTer16

p.Q532Tfs*16

Q8TC41

protein_coding

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

RNF217

SNV

Missense_Mutation

c.1568N>G

p.Phe523Cys

p.F523C

Q8TC41

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

RNF217

SNV

Missense_Mutation

rs778499520

c.1352N>A

p.Arg451Gln

p.R451Q

Q8TC41

protein_coding

tolerated(0.06)

probably_damaging(0.999)

TCGA-DM-A1D4-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

RNF217

SNV

Missense_Mutation

c.1528G>C

p.Ala510Pro

p.A510P

Q8TC41

protein_coding

deleterious(0.01)

possibly_damaging(0.896)

TCGA-AG-3592-01

Colorectum

rectum 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

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