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: NUP58

Gene summary for NUP58

Gene summary.

Gene information	Species	Human
	Gene symbol	NUP58
	Gene ID	9818
	Gene name	nucleoporin 58
	Gene Alias	NUP45
	Cytomap	13q12.13
	Gene Type	protein-coding
	GO ID	GO:0006403
	UniProtAcc	Q9BVL2

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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
9818	NUP58	LZE2T	Human	Esophagus	ESCC	2.55e-03	4.49e-01	0.082
9818	NUP58	LZE4T	Human	Esophagus	ESCC	1.39e-12	4.94e-01	0.0811
9818	NUP58	LZE7T	Human	Esophagus	ESCC	1.40e-07	5.33e-01	0.0667
9818	NUP58	LZE8T	Human	Esophagus	ESCC	2.81e-13	3.94e-01	0.067
9818	NUP58	LZE22T	Human	Esophagus	ESCC	6.57e-10	4.49e-01	0.068
9818	NUP58	LZE24T	Human	Esophagus	ESCC	7.85e-17	2.90e-01	0.0596
9818	NUP58	LZE21T	Human	Esophagus	ESCC	6.07e-05	3.15e-01	0.0655
9818	NUP58	LZE6T	Human	Esophagus	ESCC	7.29e-04	1.98e-01	0.0845
9818	NUP58	P1T-E	Human	Esophagus	ESCC	1.45e-02	3.50e-01	0.0875
9818	NUP58	P2T-E	Human	Esophagus	ESCC	3.32e-50	9.48e-01	0.1177
9818	NUP58	P4T-E	Human	Esophagus	ESCC	1.90e-15	3.35e-01	0.1323
9818	NUP58	P5T-E	Human	Esophagus	ESCC	4.55e-20	4.63e-01	0.1327
9818	NUP58	P8T-E	Human	Esophagus	ESCC	1.93e-37	5.87e-01	0.0889
9818	NUP58	P9T-E	Human	Esophagus	ESCC	1.81e-14	3.71e-01	0.1131
9818	NUP58	P10T-E	Human	Esophagus	ESCC	5.55e-36	7.35e-01	0.116
9818	NUP58	P11T-E	Human	Esophagus	ESCC	5.96e-09	5.39e-01	0.1426
9818	NUP58	P12T-E	Human	Esophagus	ESCC	8.02e-10	2.01e-01	0.1122
9818	NUP58	P15T-E	Human	Esophagus	ESCC	3.25e-30	7.17e-01	0.1149
9818	NUP58	P16T-E	Human	Esophagus	ESCC	3.99e-35	5.80e-01	0.1153
9818	NUP58	P17T-E	Human	Esophagus	ESCC	8.40e-07	3.56e-01	0.1278

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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
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

∗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:003238618	Esophagus	ESCC	regulation of intracellular transport	243/8552	337/18723	3.20e-23	7.25e-21	243
GO:003450418	Esophagus	ESCC	protein localization to nucleus	211/8552	290/18723	4.06e-21	6.60e-19	211
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: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:0033157110	Esophagus	ESCC	regulation of intracellular protein transport	169/8552	229/18723	3.31e-18	3.23e-16	169
GO:001593117	Esophagus	ESCC	nucleobase-containing compound transport	162/8552	222/18723	9.87e-17	7.93e-15	162
GO:0046822110	Esophagus	ESCC	regulation of nucleocytoplasmic transport	88/8552	106/18723	1.88e-15	1.19e-13	88
GO:001703818	Esophagus	ESCC	protein import	149/8552	206/18723	5.90e-15	3.31e-13	149
GO:190018018	Esophagus	ESCC	regulation of protein localization to nucleus	102/8552	136/18723	2.84e-12	1.13e-10	102
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:190458914	Esophagus	ESCC	regulation of protein import	49/8552	63/18723	1.91e-07	2.97e-06	49
GO:004230614	Esophagus	ESCC	regulation of protein import into nucleus	46/8552	60/18723	9.55e-07	1.21e-05	46
GO:007259422	Liver	HCC	establishment of protein localization to organelle	299/7958	422/18723	1.06e-32	6.10e-30	299

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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
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
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
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
hsa0501428	Oral cavity	OSCC	Amyotrophic lateral sclerosis	246/3704	364/8465	6.65e-21	1.11e-18	5.67e-19	246
hsa030136	Oral cavity	OSCC	Nucleocytoplasmic transport	82/3704	108/8465	7.93e-12	1.33e-10	6.77e-11	82
hsa05014112	Oral cavity	OSCC	Amyotrophic lateral sclerosis	246/3704	364/8465	6.65e-21	1.11e-18	5.67e-19	246
hsa0301311	Oral cavity	OSCC	Nucleocytoplasmic transport	82/3704	108/8465	7.93e-12	1.33e-10	6.77e-11	82
hsa0501445	Oral cavity	EOLP	Amyotrophic lateral sclerosis	93/1218	364/8465	7.07e-09	1.14e-07	6.74e-08	93
hsa030134	Oral cavity	EOLP	Nucleocytoplasmic transport	34/1218	108/8465	4.24e-06	2.91e-05	1.72e-05	34
hsa0501455	Oral cavity	EOLP	Amyotrophic lateral sclerosis	93/1218	364/8465	7.07e-09	1.14e-07	6.74e-08	93
hsa030135	Oral cavity	EOLP	Nucleocytoplasmic transport	34/1218	108/8465	4.24e-06	2.91e-05	1.72e-05	34
hsa0501462	Oral cavity	NEOLP	Amyotrophic lateral sclerosis	95/1112	364/8465	8.76e-12	3.98e-10	2.50e-10	95
hsa0501472	Oral cavity	NEOLP	Amyotrophic lateral sclerosis	95/1112	364/8465	8.76e-12	3.98e-10	2.50e-10	95

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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

NUP58

SNV

Missense_Mutation

c.628N>T

p.Thr210Ser

p.T210S

Q9BVL2

protein_coding

tolerated(0.31)

benign(0.001)

TCGA-A8-A09I-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

NUP58

SNV

Missense_Mutation

c.947C>T

p.Ala316Val

p.A316V

Q9BVL2

protein_coding

deleterious(0)

benign(0.441)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NUP58

SNV

Missense_Mutation

c.236N>A

p.Gly79Glu

p.G79E

Q9BVL2

protein_coding

tolerated(0.11)

probably_damaging(0.999)

TCGA-BH-A18T-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NUP58

SNV

Missense_Mutation

novel

c.478G>T

p.Ala160Ser

p.A160S

Q9BVL2

protein_coding

tolerated(0.29)

benign(0.001)

TCGA-E2-A1IG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

NUP58

SNV

Missense_Mutation

novel

c.1690G>A

p.Ala564Thr

p.A564T

Q9BVL2

protein_coding

deleterious(0.01)

probably_damaging(0.995)

TCGA-E9-A2JS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cyclophosphamide

NUP58

SNV

Missense_Mutation

c.1060N>C

p.Glu354Gln

p.E354Q

Q9BVL2

protein_coding

tolerated(0.05)

benign(0.251)

TCGA-EW-A1J5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

NUP58

insertion

Frame_Shift_Ins

novel

c.563_564insATATAATCTTACTTAT

p.Gly189TyrfsTer31

p.G189Yfs*31

Q9BVL2

protein_coding

TCGA-AN-A041-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NUP58

SNV

Missense_Mutation

c.743N>G

p.Pro248Arg

p.P248R

Q9BVL2

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-BI-A0VR-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

NUP58

SNV

Missense_Mutation

c.600G>C

p.Leu200Phe

p.L200F

Q9BVL2

protein_coding

deleterious(0.04)

probably_damaging(0.996)

TCGA-C5-A1ML-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NUP58

SNV

Missense_Mutation

c.21N>A

p.Phe7Leu

p.F7L

Q9BVL2

protein_coding

tolerated(0.12)

probably_damaging(0.916)

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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