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: RANBP2

Gene summary for RANBP2

Gene summary.

Gene information	Species	Human
	Gene symbol	RANBP2
	Gene ID	5903
	Gene name	RAN binding protein 2
	Gene Alias	ADANE
	Cytomap	2q13
	Gene Type	protein-coding
	GO ID	GO:0000413
	UniProtAcc	P49792

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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
5903	RANBP2	LZE4T	Human	Esophagus	ESCC	3.73e-17	5.99e-01	0.0811
5903	RANBP2	LZE7T	Human	Esophagus	ESCC	1.54e-10	8.92e-01	0.0667
5903	RANBP2	LZE20T	Human	Esophagus	ESCC	2.24e-09	1.72e-01	0.0662
5903	RANBP2	LZE24T	Human	Esophagus	ESCC	3.68e-14	4.31e-01	0.0596
5903	RANBP2	LZE21T	Human	Esophagus	ESCC	5.11e-06	1.26e-01	0.0655
5903	RANBP2	P1T-E	Human	Esophagus	ESCC	1.41e-11	3.67e-01	0.0875
5903	RANBP2	P2T-E	Human	Esophagus	ESCC	1.90e-33	5.12e-01	0.1177
5903	RANBP2	P4T-E	Human	Esophagus	ESCC	7.81e-12	4.11e-01	0.1323
5903	RANBP2	P5T-E	Human	Esophagus	ESCC	3.10e-20	2.64e-01	0.1327
5903	RANBP2	P8T-E	Human	Esophagus	ESCC	2.69e-22	3.96e-01	0.0889
5903	RANBP2	P9T-E	Human	Esophagus	ESCC	6.25e-13	3.39e-01	0.1131
5903	RANBP2	P10T-E	Human	Esophagus	ESCC	1.09e-43	7.94e-01	0.116
5903	RANBP2	P11T-E	Human	Esophagus	ESCC	3.88e-12	6.18e-01	0.1426
5903	RANBP2	P12T-E	Human	Esophagus	ESCC	3.65e-24	4.76e-01	0.1122
5903	RANBP2	P15T-E	Human	Esophagus	ESCC	1.56e-23	6.92e-01	0.1149
5903	RANBP2	P16T-E	Human	Esophagus	ESCC	8.95e-22	4.87e-01	0.1153
5903	RANBP2	P20T-E	Human	Esophagus	ESCC	4.25e-15	2.65e-01	0.1124
5903	RANBP2	P21T-E	Human	Esophagus	ESCC	1.16e-32	7.03e-01	0.1617
5903	RANBP2	P22T-E	Human	Esophagus	ESCC	4.24e-24	2.30e-01	0.1236
5903	RANBP2	P23T-E	Human	Esophagus	ESCC	3.00e-20	4.29e-01	0.108

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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
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:0072594110	Esophagus	ESCC	establishment of protein localization to organelle	311/8552	422/18723	3.02e-32	2.13e-29	311
GO:0006913110	Esophagus	ESCC	nucleocytoplasmic transport	230/8552	301/18723	6.04e-28	2.02e-25	230
GO:0051169110	Esophagus	ESCC	nuclear transport	230/8552	301/18723	6.04e-28	2.02e-25	230
GO:0006403110	Esophagus	ESCC	RNA localization	166/8552	201/18723	1.95e-27	6.18e-25	166
GO:003450418	Esophagus	ESCC	protein localization to nucleus	211/8552	290/18723	4.06e-21	6.60e-19	211
GO:0006457110	Esophagus	ESCC	protein folding	163/8552	212/18723	1.13e-20	1.74e-18	163
GO:005123617	Esophagus	ESCC	establishment of RNA localization	134/8552	166/18723	1.23e-20	1.81e-18	134
GO:005102815	Esophagus	ESCC	mRNA transport	110/8552	130/18723	2.76e-20	3.80e-18	110
GO:001820514	Esophagus	ESCC	peptidyl-lysine modification	259/8552	376/18723	3.90e-20	5.26e-18	259
GO:005065717	Esophagus	ESCC	nucleic acid transport	131/8552	163/18723	6.94e-20	8.46e-18	131
GO:005065817	Esophagus	ESCC	RNA transport	131/8552	163/18723	6.94e-20	8.46e-18	131
GO:001593117	Esophagus	ESCC	nucleobase-containing compound transport	162/8552	222/18723	9.87e-17	7.93e-15	162
GO:001703818	Esophagus	ESCC	protein import	149/8552	206/18723	5.90e-15	3.31e-13	149
GO:005117014	Esophagus	ESCC	import into nucleus	111/8552	159/18723	5.69e-10	1.44e-08	111
GO:000660613	Esophagus	ESCC	protein import into nucleus	108/8552	155/18723	1.16e-09	2.77e-08	108
GO:00059969	Esophagus	ESCC	monosaccharide metabolic process	159/8552	257/18723	1.11e-07	1.81e-06	159
GO:001820816	Esophagus	ESCC	peptidyl-proline modification	46/8552	58/18723	1.59e-07	2.51e-06	46
GO:00193189	Esophagus	ESCC	hexose metabolic process	147/8552	237/18723	2.63e-07	3.94e-06	147
GO:001692512	Esophagus	ESCC	protein sumoylation	41/8552	53/18723	2.49e-06	2.86e-05	41
GO:00618428	Esophagus	ESCC	microtubule organizing center localization	28/8552	33/18723	3.80e-06	4.12e-05	28

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05014210	Esophagus	ESCC	Amyotrophic lateral sclerosis	266/4205	364/8465	1.31e-20	2.20e-18	1.13e-18	266
hsa0301321	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa032509	Esophagus	ESCC	Viral life cycle - HIV-1	54/4205	63/8465	2.01e-09	2.17e-08	1.11e-08	54
hsa0501438	Esophagus	ESCC	Amyotrophic lateral sclerosis	266/4205	364/8465	1.31e-20	2.20e-18	1.13e-18	266
hsa0301331	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa0325014	Esophagus	ESCC	Viral life cycle - HIV-1	54/4205	63/8465	2.01e-09	2.17e-08	1.11e-08	54
hsa0501422	Liver	HCC	Amyotrophic lateral sclerosis	252/4020	364/8465	8.85e-18	7.41e-16	4.12e-16	252
hsa03013	Liver	HCC	Nucleocytoplasmic transport	81/4020	108/8465	4.28e-09	6.83e-08	3.80e-08	81
hsa032502	Liver	HCC	Viral life cycle - HIV-1	46/4020	63/8465	3.25e-05	1.88e-04	1.04e-04	46
hsa0501432	Liver	HCC	Amyotrophic lateral sclerosis	252/4020	364/8465	8.85e-18	7.41e-16	4.12e-16	252
hsa030131	Liver	HCC	Nucleocytoplasmic transport	81/4020	108/8465	4.28e-09	6.83e-08	3.80e-08	81
hsa0325011	Liver	HCC	Viral life cycle - HIV-1	46/4020	63/8465	3.25e-05	1.88e-04	1.04e-04	46
hsa0501426	Prostate	BPH	Amyotrophic lateral sclerosis	151/1718	364/8465	3.37e-21	1.01e-19	6.25e-20	151
hsa032504	Prostate	BPH	Viral life cycle - HIV-1	24/1718	63/8465	8.32e-04	3.98e-03	2.46e-03	24
hsa05014111	Prostate	BPH	Amyotrophic lateral sclerosis	151/1718	364/8465	3.37e-21	1.01e-19	6.25e-20	151
hsa0325012	Prostate	BPH	Viral life cycle - HIV-1	24/1718	63/8465	8.32e-04	3.98e-03	2.46e-03	24
hsa0501427	Prostate	Tumor	Amyotrophic lateral sclerosis	155/1791	364/8465	3.41e-21	1.13e-19	6.99e-20	155
hsa0325021	Prostate	Tumor	Viral life cycle - HIV-1	25/1791	63/8465	6.13e-04	3.07e-03	1.91e-03	25
hsa0501436	Prostate	Tumor	Amyotrophic lateral sclerosis	155/1791	364/8465	3.41e-21	1.13e-19	6.99e-20	155
hsa032503	Prostate	Tumor	Viral life cycle - HIV-1	25/1791	63/8465	6.13e-04	3.07e-03	1.91e-03	25

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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

RANBP2

SNV

Missense_Mutation

c.2421G>C

p.Gln807His

p.Q807H

P49792

protein_coding

tolerated(0.07)

benign(0.045)

TCGA-A2-A0EQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

RANBP2

SNV

Missense_Mutation

c.2389C>G

p.Pro797Ala

p.P797A

P49792

protein_coding

deleterious(0)

benign(0.444)

TCGA-A7-A5ZX-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

RANBP2

SNV

Missense_Mutation

c.8368N>C

p.Phe2790Leu

p.F2790L

P49792

protein_coding

tolerated(0.6)

benign(0)

TCGA-A8-A09A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

RANBP2

SNV

Missense_Mutation

c.7958N>C

p.Leu2653Pro

p.L2653P

P49792

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RANBP2

SNV

Missense_Mutation

c.3368N>G

p.Ser1123Cys

p.S1123C

P49792

protein_coding

tolerated(0.18)

benign(0.001)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RANBP2

SNV

Missense_Mutation

novel

c.4334N>G

p.Asn1445Ser

p.N1445S

P49792

protein_coding

tolerated(0.34)

benign(0)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RANBP2

SNV

Missense_Mutation

rs769492789

c.8032N>A

p.Glu2678Lys

p.E2678K

P49792

protein_coding

deleterious(0)

possibly_damaging(0.702)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RANBP2

SNV

Missense_Mutation

novel

c.9362T>C

p.Val3121Ala

p.V3121A

P49792

protein_coding

deleterious(0.02)

benign(0.007)

TCGA-AN-A0FV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

RANBP2

SNV

Missense_Mutation

novel

c.3164N>T

p.Pro1055Leu

p.P1055L

P49792

protein_coding

deleterious(0.01)

benign(0.245)

TCGA-AR-A2LR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

RANBP2

SNV

Missense_Mutation

novel

c.6308G>C

p.Arg2103Thr

p.R2103T

P49792

protein_coding

deleterious(0)

possibly_damaging(0.754)

TCGA-AR-A5QQ-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

carboplatin

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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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