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: NUP85

Gene summary for NUP85

Gene summary.

Gene information	Species	Human
	Gene symbol	NUP85
	Gene ID	79902
	Gene name	nucleoporin 85
	Gene Alias	FROUNT
	Cytomap	17q25.1
	Gene Type	protein-coding
	GO ID	GO:0001655
	UniProtAcc	Q9BW27

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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
79902	NUP85	LZE2T	Human	Esophagus	ESCC	1.65e-02	2.56e-01	0.082
79902	NUP85	LZE4T	Human	Esophagus	ESCC	3.16e-04	5.79e-02	0.0811
79902	NUP85	LZE8T	Human	Esophagus	ESCC	1.21e-05	1.48e-01	0.067
79902	NUP85	LZE20T	Human	Esophagus	ESCC	3.72e-02	6.70e-02	0.0662
79902	NUP85	LZE22T	Human	Esophagus	ESCC	1.14e-03	1.70e-01	0.068
79902	NUP85	LZE24T	Human	Esophagus	ESCC	3.56e-10	2.13e-01	0.0596
79902	NUP85	LZE21T	Human	Esophagus	ESCC	3.58e-05	2.25e-01	0.0655
79902	NUP85	LZE6T	Human	Esophagus	ESCC	4.93e-04	1.03e-01	0.0845
79902	NUP85	P1T-E	Human	Esophagus	ESCC	1.39e-04	1.70e-01	0.0875
79902	NUP85	P2T-E	Human	Esophagus	ESCC	1.11e-12	2.09e-01	0.1177
79902	NUP85	P4T-E	Human	Esophagus	ESCC	9.78e-10	1.18e-01	0.1323
79902	NUP85	P8T-E	Human	Esophagus	ESCC	1.23e-11	2.61e-01	0.0889
79902	NUP85	P9T-E	Human	Esophagus	ESCC	1.44e-03	1.17e-01	0.1131
79902	NUP85	P10T-E	Human	Esophagus	ESCC	8.78e-22	3.93e-01	0.116
79902	NUP85	P11T-E	Human	Esophagus	ESCC	2.69e-07	3.10e-01	0.1426
79902	NUP85	P12T-E	Human	Esophagus	ESCC	1.43e-21	3.20e-01	0.1122
79902	NUP85	P15T-E	Human	Esophagus	ESCC	1.06e-18	3.34e-01	0.1149
79902	NUP85	P16T-E	Human	Esophagus	ESCC	1.08e-14	2.22e-01	0.1153
79902	NUP85	P17T-E	Human	Esophagus	ESCC	4.02e-04	2.02e-01	0.1278
79902	NUP85	P20T-E	Human	Esophagus	ESCC	4.44e-39	8.46e-01	0.1124

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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

∗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:001703816	Oral cavity	LP	protein import	95/4623	206/18723	1.55e-11	1.13e-09	95
GO:005065715	Oral cavity	LP	nucleic acid transport	78/4623	163/18723	1.11e-10	6.44e-09	78
GO:005065815	Oral cavity	LP	RNA transport	78/4623	163/18723	1.11e-10	6.44e-09	78
GO:005123615	Oral cavity	LP	establishment of RNA localization	79/4623	166/18723	1.18e-10	6.81e-09	79
GO:001593115	Oral cavity	LP	nucleobase-containing compound transport	95/4623	222/18723	2.23e-09	9.98e-08	95
GO:005102814	Oral cavity	LP	mRNA transport	62/4623	130/18723	1.03e-08	3.90e-07	62
GO:005116818	Oral cavity	LP	nuclear export	68/4623	154/18723	9.55e-08	3.13e-06	68
GO:007116611	Oral cavity	LP	ribonucleoprotein complex localization	38/4623	77/18723	2.47e-06	5.43e-05	38
GO:000640511	Oral cavity	LP	RNA export from nucleus	40/4623	84/18723	4.24e-06	8.71e-05	40
GO:005117013	Oral cavity	LP	import into nucleus	65/4623	159/18723	4.78e-06	9.69e-05	65
GO:007142611	Oral cavity	LP	ribonucleoprotein complex export from nucleus	37/4623	76/18723	5.02e-06	1.01e-04	37
GO:000660612	Oral cavity	LP	protein import into nucleus	62/4623	155/18723	1.76e-05	3.04e-04	62
GO:003150313	Oral cavity	LP	protein-containing complex localization	82/4623	220/18723	2.08e-05	3.44e-04	82
GO:000640611	Oral cavity	LP	mRNA export from nucleus	28/4623	59/18723	1.22e-04	1.43e-03	28
GO:007142711	Oral cavity	LP	mRNA-containing ribonucleoprotein complex export from nucleus	28/4623	59/18723	1.22e-04	1.43e-03	28
GO:009758115	Oral cavity	LP	lamellipodium organization	37/4623	90/18723	4.36e-04	4.18e-03	37
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

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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
hsa0501429	Oral cavity	LP	Amyotrophic lateral sclerosis	197/2418	364/8465	1.25e-25	1.39e-23	8.93e-24	197
hsa030132	Oral cavity	LP	Nucleocytoplasmic transport	53/2418	108/8465	4.68e-06	4.10e-05	2.64e-05	53
hsa0501437	Oral cavity	LP	Amyotrophic lateral sclerosis	197/2418	364/8465	1.25e-25	1.39e-23	8.93e-24	197
hsa030133	Oral cavity	LP	Nucleocytoplasmic transport	53/2418	108/8465	4.68e-06	4.10e-05	2.64e-05	53

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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

NUP85

SNV

Missense_Mutation

novel

c.1616G>T

p.Gly539Val

p.G539V

Q9BW27

protein_coding

deleterious(0.05)

probably_damaging(0.997)

TCGA-A2-A3XT-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

NUP85

SNV

Missense_Mutation

novel

c.224N>T

p.Ser75Phe

p.S75F

Q9BW27

protein_coding

deleterious(0)

possibly_damaging(0.792)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

NUP85

SNV

Missense_Mutation

c.827N>T

p.Thr276Ile

p.T276I

Q9BW27

protein_coding

deleterious(0)

benign(0.112)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

NUP85

SNV

Missense_Mutation

novel

c.673N>T

p.Ala225Ser

p.A225S

Q9BW27

protein_coding

tolerated(0.84)

benign(0.001)

TCGA-S3-AA10-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

NUP85

insertion

Frame_Shift_Ins

novel

c.1748_1749insTTTTAAT

p.Leu584PhefsTer18

p.L584Ffs*18

Q9BW27

protein_coding

TCGA-A2-A0EQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

NUP85

insertion

Nonsense_Mutation

novel

c.1749_1750insCATGACTCTTGTTATGTATTTTGA

p.Pro583_Leu584insHisAspSerCysTyrValPheTer

p.P583_L584insHDSCYVF*

Q9BW27

protein_coding

TCGA-A2-A0EQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

NUP85

deletion

In_Frame_Del

c.1692_1694delNNN

p.Thr565del

p.T565del

Q9BW27

protein_coding

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NUP85

SNV

Missense_Mutation

c.13N>A

p.Asp5Asn

p.D5N

Q9BW27

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.996)

TCGA-EK-A2RJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NUP85

SNV

Missense_Mutation

c.320N>T

p.Ser107Leu

p.S107L

Q9BW27

protein_coding

deleterious(0)

possibly_damaging(0.826)

TCGA-IR-A3LA-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NUP85

SNV

Missense_Mutation

c.234N>G

p.Ile78Met

p.I78M

Q9BW27

protein_coding

deleterious(0)

probably_damaging(0.979)

TCGA-Q1-A73R-01

Cervix

cervical & endocervical cancer

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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