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: NUP214

Gene summary for NUP214

Gene summary.

Gene information	Species	Human
	Gene symbol	NUP214
	Gene ID	8021
	Gene name	nucleoporin 214
	Gene Alias	CAIN
	Cytomap	9q34.13
	Gene Type	protein-coding
	GO ID	GO:0000278
	UniProtAcc	P35658

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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
8021	NUP214	CCI_2	Human	Cervix	CC	3.48e-11	1.13e+00	0.5249
8021	NUP214	CCI_3	Human	Cervix	CC	2.57e-05	5.81e-01	0.516
8021	NUP214	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	1.84e-05	-2.18e-02	-0.1869
8021	NUP214	GSM6177620_NYU_UCEC1_lib2_lib2	Human	Endometrium	EEC	1.28e-09	-3.63e-02	-0.1875
8021	NUP214	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	1.31e-06	-1.36e-02	-0.1883
8021	NUP214	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	2.53e-02	2.32e-02	-0.1934
8021	NUP214	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	5.95e-08	-4.51e-02	-0.1917
8021	NUP214	GSM6177622_NYU_UCEC3_lib2_lib2	Human	Endometrium	EEC	5.70e-10	-1.21e-02	-0.1916
8021	NUP214	LZE2T	Human	Esophagus	ESCC	8.90e-03	5.21e-01	0.082
8021	NUP214	LZE4T	Human	Esophagus	ESCC	5.60e-15	2.20e-01	0.0811
8021	NUP214	LZE7T	Human	Esophagus	ESCC	3.61e-07	4.05e-01	0.0667
8021	NUP214	LZE8T	Human	Esophagus	ESCC	1.22e-03	1.71e-01	0.067
8021	NUP214	LZE20T	Human	Esophagus	ESCC	3.44e-11	3.59e-01	0.0662
8021	NUP214	LZE21D1	Human	Esophagus	HGIN	2.30e-02	3.54e-01	0.0632
8021	NUP214	LZE24T	Human	Esophagus	ESCC	1.43e-05	2.44e-01	0.0596
8021	NUP214	LZE21T	Human	Esophagus	ESCC	3.45e-02	1.41e-01	0.0655
8021	NUP214	LZE6T	Human	Esophagus	ESCC	1.57e-03	1.95e-01	0.0845
8021	NUP214	P2T-E	Human	Esophagus	ESCC	6.86e-41	6.63e-01	0.1177
8021	NUP214	P4T-E	Human	Esophagus	ESCC	6.27e-09	2.51e-01	0.1323
8021	NUP214	P5T-E	Human	Esophagus	ESCC	2.48e-12	2.35e-01	0.1327

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
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

∗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:00725949	Cervix	CC	establishment of protein localization to organelle	99/2311	422/18723	1.23e-10	2.11e-08	99
GO:00069139	Cervix	CC	nucleocytoplasmic transport	71/2311	301/18723	4.04e-08	2.54e-06	71
GO:00511699	Cervix	CC	nuclear transport	71/2311	301/18723	4.04e-08	2.54e-06	71
GO:00345048	Cervix	CC	protein localization to nucleus	68/2311	290/18723	9.91e-08	5.25e-06	68
GO:00468229	Cervix	CC	regulation of nucleocytoplasmic transport	31/2311	106/18723	2.68e-06	7.87e-05	31
GO:00323868	Cervix	CC	regulation of intracellular transport	71/2311	337/18723	3.70e-06	9.74e-05	71
GO:00170388	Cervix	CC	protein import	48/2311	206/18723	8.62e-06	1.98e-04	48
GO:00511689	Cervix	CC	nuclear export	38/2311	154/18723	1.86e-05	3.46e-04	38
GO:00511707	Cervix	CC	import into nucleus	38/2311	159/18723	3.98e-05	6.18e-04	38
GO:00512368	Cervix	CC	establishment of RNA localization	39/2311	166/18723	4.76e-05	7.25e-04	39
GO:00066067	Cervix	CC	protein import into nucleus	37/2311	155/18723	5.13e-05	7.71e-04	37
GO:00506578	Cervix	CC	nucleic acid transport	38/2311	163/18723	7.06e-05	9.85e-04	38
GO:00506588	Cervix	CC	RNA transport	38/2311	163/18723	7.06e-05	9.85e-04	38
GO:000640310	Cervix	CC	RNA localization	43/2311	201/18723	2.00e-04	2.29e-03	43
GO:00510284	Cervix	CC	mRNA transport	31/2311	130/18723	2.05e-04	2.33e-03	31
GO:00066116	Cervix	CC	protein export from nucleus	17/2311	57/18723	3.61e-04	3.75e-03	17
GO:00159318	Cervix	CC	nucleobase-containing compound transport	43/2311	222/18723	1.72e-03	1.30e-02	43
GO:00714262	Cervix	CC	ribonucleoprotein complex export from nucleus	18/2311	76/18723	4.45e-03	2.71e-02	18
GO:00711662	Cervix	CC	ribonucleoprotein complex localization	18/2311	77/18723	5.15e-03	3.03e-02	18
GO:00064054	Cervix	CC	RNA export from nucleus	19/2311	84/18723	6.02e-03	3.43e-02	19

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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
hsa0501425	Endometrium	EEC	Amyotrophic lateral sclerosis	128/1237	364/8465	9.83e-24	4.04e-22	3.01e-22	128
hsa0501435	Endometrium	EEC	Amyotrophic lateral sclerosis	128/1237	364/8465	9.83e-24	4.04e-22	3.01e-22	128
hsa0501430	Esophagus	HGIN	Amyotrophic lateral sclerosis	140/1383	364/8465	2.13e-25	1.16e-23	9.19e-24	140
hsa030137	Esophagus	HGIN	Nucleocytoplasmic transport	31/1383	108/8465	8.29e-04	7.95e-03	6.31e-03	31
hsa05014113	Esophagus	HGIN	Amyotrophic lateral sclerosis	140/1383	364/8465	2.13e-25	1.16e-23	9.19e-24	140
hsa0301312	Esophagus	HGIN	Nucleocytoplasmic transport	31/1383	108/8465	8.29e-04	7.95e-03	6.31e-03	31
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

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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

NUP214

SNV

Missense_Mutation

novel

c.1931N>C

p.Leu644Ser

p.L644S

P35658

protein_coding

tolerated(0.51)

benign(0)

TCGA-A7-A3J0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

anastrazole

NUP214

SNV

Missense_Mutation

c.1030N>C

p.Glu344Gln

p.E344Q

P35658

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-A8-A09I-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

NUP214

SNV

Missense_Mutation

c.3387N>C

p.Lys1129Asn

p.K1129N

P35658

protein_coding

deleterious(0.01)

possibly_damaging(0.73)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NUP214

SNV

Missense_Mutation

c.3961N>A

p.Leu1321Met

p.L1321M

P35658

protein_coding

deleterious_low_confidence(0.03)

probably_damaging(0.984)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NUP214

SNV

Missense_Mutation

c.197A>G

p.Asn66Ser

p.N66S

P35658

protein_coding

tolerated(0.17)

benign(0.001)

TCGA-BH-A0EB-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

NUP214

SNV

Missense_Mutation

c.3920C>T

p.Ser1307Phe

p.S1307F

P35658

protein_coding

deleterious(0.01)

possibly_damaging(0.568)

TCGA-C8-A1HL-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

NUP214

SNV

Missense_Mutation

c.4487N>T

p.Ala1496Val

p.A1496V

P35658

protein_coding

tolerated_low_confidence(0.1)

benign(0.006)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

NUP214

SNV

Missense_Mutation

c.4288N>G

p.Thr1430Ala

p.T1430A

P35658

protein_coding

tolerated_low_confidence(0.64)

benign(0)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NUP214

insertion

Nonsense_Mutation

novel

c.5849_5850insCTCCCCCTCCTCCAGTCCTCTCCTTTCACTTTGCTTGTGA

p.Gly1951SerfsTer13

p.G1951Sfs*13

P35658

protein_coding

TCGA-A7-A0CD-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

NUP214

insertion

Frame_Shift_Ins

novel

c.3185_3186insGTATTTT

p.Gln1063TyrfsTer7

p.Q1063Yfs*7

P35658

protein_coding

TCGA-BH-A0BV-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

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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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