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: NUP93

Gene summary for NUP93

Gene summary.

Gene information	Species	Human
	Gene symbol	NUP93
	Gene ID	9688
	Gene name	nucleoporin 93
	Gene Alias	NIC96
	Cytomap	16q13
	Gene Type	protein-coding
	GO ID	GO:0006403
	UniProtAcc	Q8N1F7

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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
9688	NUP93	CCI_2	Human	Cervix	CC	9.20e-08	7.17e-01	0.5249
9688	NUP93	CCI_3	Human	Cervix	CC	9.99e-03	5.30e-01	0.516
9688	NUP93	LZE2T	Human	Esophagus	ESCC	1.10e-04	5.04e-01	0.082
9688	NUP93	LZE4T	Human	Esophagus	ESCC	4.29e-04	1.14e-01	0.0811
9688	NUP93	LZE20T	Human	Esophagus	ESCC	3.27e-02	1.28e-01	0.0662
9688	NUP93	LZE22T	Human	Esophagus	ESCC	4.26e-02	1.64e-01	0.068
9688	NUP93	LZE24T	Human	Esophagus	ESCC	7.81e-10	1.81e-01	0.0596
9688	NUP93	LZE21T	Human	Esophagus	ESCC	8.50e-05	2.42e-01	0.0655
9688	NUP93	LZE6T	Human	Esophagus	ESCC	2.25e-03	1.77e-01	0.0845
9688	NUP93	P1T-E	Human	Esophagus	ESCC	2.56e-04	3.57e-01	0.0875
9688	NUP93	P2T-E	Human	Esophagus	ESCC	2.76e-17	2.18e-01	0.1177
9688	NUP93	P4T-E	Human	Esophagus	ESCC	3.19e-15	4.12e-01	0.1323
9688	NUP93	P5T-E	Human	Esophagus	ESCC	1.95e-09	2.65e-01	0.1327
9688	NUP93	P8T-E	Human	Esophagus	ESCC	2.40e-10	1.85e-01	0.0889
9688	NUP93	P9T-E	Human	Esophagus	ESCC	1.40e-02	8.43e-02	0.1131
9688	NUP93	P10T-E	Human	Esophagus	ESCC	1.31e-07	1.52e-01	0.116
9688	NUP93	P11T-E	Human	Esophagus	ESCC	1.32e-07	2.64e-01	0.1426
9688	NUP93	P12T-E	Human	Esophagus	ESCC	1.96e-14	3.13e-01	0.1122
9688	NUP93	P15T-E	Human	Esophagus	ESCC	3.41e-10	2.47e-01	0.1149
9688	NUP93	P16T-E	Human	Esophagus	ESCC	1.12e-13	1.86e-01	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
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

∗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:00511709	Oral cavity	OSCC	import into nucleus	100/7305	159/18723	8.67e-10	2.15e-08	100
GO:00066069	Oral cavity	OSCC	protein import into nucleus	97/7305	155/18723	2.27e-09	5.30e-08	97
GO:00069974	Oral cavity	OSCC	nucleus organization	85/7305	133/18723	5.12e-09	1.12e-07	85
GO:00064063	Oral cavity	OSCC	mRNA export from nucleus	45/7305	59/18723	6.19e-09	1.31e-07	45
GO:00714273	Oral cavity	OSCC	mRNA-containing ribonucleoprotein complex export from nucleus	45/7305	59/18723	6.19e-09	1.31e-07	45
GO:00069982	Oral cavity	OSCC	nuclear envelope organization	37/7305	47/18723	3.19e-08	6.12e-07	37
GO:00315034	Oral cavity	OSCC	protein-containing complex localization	123/7305	220/18723	2.54e-07	4.00e-06	123
GO:00069993	Oral cavity	OSCC	nuclear pore organization	12/7305	14/18723	4.62e-04	2.76e-03	12
GO:00469315	Oral cavity	OSCC	pore complex assembly	15/7305	20/18723	1.19e-03	5.99e-03	15
GO:00071789	Oral cavity	OSCC	transmembrane receptor protein serine/threonine kinase signaling pathway	165/7305	355/18723	2.31e-03	1.02e-02	165
GO:007259427	Skin	cSCC	establishment of protein localization to organelle	213/4864	422/18723	1.40e-27	5.15e-25	213
GO:000691324	Skin	cSCC	nucleocytoplasmic transport	162/4864	301/18723	4.20e-25	1.10e-22	162
GO:005116924	Skin	cSCC	nuclear transport	162/4864	301/18723	4.20e-25	1.10e-22	162
GO:0006403111	Skin	cSCC	RNA localization	120/4864	201/18723	4.17e-24	1.01e-21	120
GO:0051168111	Skin	cSCC	nuclear export	91/4864	154/18723	3.33e-18	4.18e-16	91
GO:0034504110	Skin	cSCC	protein localization to nucleus	143/4864	290/18723	8.98e-18	1.02e-15	143
GO:005065719	Skin	cSCC	nucleic acid transport	92/4864	163/18723	1.35e-16	1.33e-14	92
GO:005065819	Skin	cSCC	RNA transport	92/4864	163/18723	1.35e-16	1.33e-14	92
GO:005123619	Skin	cSCC	establishment of RNA localization	93/4864	166/18723	1.78e-16	1.69e-14	93
GO:005102816	Skin	cSCC	mRNA transport	77/4864	130/18723	1.06e-15	8.95e-14	77

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0501418	Cervix	CC	Amyotrophic lateral sclerosis	103/1267	364/8465	1.79e-11	4.47e-10	2.64e-10	103
hsa0501419	Cervix	CC	Amyotrophic lateral sclerosis	103/1267	364/8465	1.79e-11	4.47e-10	2.64e-10	103
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
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

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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

NUP93

SNV

Missense_Mutation

rs371707121

c.1609N>T

p.Arg537Trp

p.R537W

Q8N1F7

protein_coding

deleterious(0)

probably_damaging(0.991)

TCGA-A7-A6VV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

NUP93

SNV

Missense_Mutation

rs528073782

c.40G>A

p.Glu14Lys

p.E14K

Q8N1F7

protein_coding

deleterious(0.05)

benign(0.013)

TCGA-BH-A209-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NUP93

SNV

Missense_Mutation

rs528073782

c.40N>A

p.Glu14Lys

p.E14K

Q8N1F7

protein_coding

deleterious(0.05)

benign(0.013)

TCGA-BH-A2L8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

NUP93

SNV

Missense_Mutation

rs528073782

c.40G>A

p.Glu14Lys

p.E14K

Q8N1F7

protein_coding

deleterious(0.05)

benign(0.013)

TCGA-E2-A10C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

NUP93

SNV

Missense_Mutation

rs528073782

c.40G>A

p.Glu14Lys

p.E14K

Q8N1F7

protein_coding

deleterious(0.05)

benign(0.013)

TCGA-E9-A1NC-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

NUP93

insertion

Nonsense_Mutation

novel

c.195_196insGCAACAGAGCAAGACCCTGTCTGAAAATAAAATAAAATAGAC

p.Gly65_Ser66insAlaThrGluGlnAspProValTerLysTerAsnLysIleAsp

p.G65_S66insATEQDPV*K*NKID

Q8N1F7

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NUP93

deletion

Frame_Shift_Del

novel

c.1390delC

p.Gln464LysfsTer5

p.Q464Kfs*5

Q8N1F7

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

NUP93

SNV

Missense_Mutation

novel

c.773C>T

p.Ala258Val

p.A258V

Q8N1F7

protein_coding

deleterious(0.01)

possibly_damaging(0.78)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NUP93

SNV

Missense_Mutation

novel

c.1600C>A

p.Leu534Met

p.L534M

Q8N1F7

protein_coding

tolerated(0.25)

benign(0.123)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NUP93

SNV

Missense_Mutation

rs145578512

c.1000N>A

p.Ala334Thr

p.A334T

Q8N1F7

protein_coding

deleterious(0.05)

probably_damaging(0.94)

TCGA-C5-A1MH-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

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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