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: NUTF2

Gene summary for NUTF2

Gene summary.

Gene information	Species	Human
	Gene symbol	NUTF2
	Gene ID	10204
	Gene name	nuclear transport factor 2
	Gene Alias	NTF-2
	Cytomap	16q22.1
	Gene Type	protein-coding
	GO ID	GO:0001816
	UniProtAcc	A0A024R6Y2

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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
10204	NUTF2	HTA11_2487_2000001011	Human	Colorectum	SER	8.78e-07	2.78e-01	-0.1808
10204	NUTF2	HTA11_1938_2000001011	Human	Colorectum	AD	7.33e-09	4.82e-01	-0.0811
10204	NUTF2	HTA11_78_2000001011	Human	Colorectum	AD	7.10e-04	2.58e-01	-0.1088
10204	NUTF2	HTA11_347_2000001011	Human	Colorectum	AD	8.66e-12	3.65e-01	-0.1954
10204	NUTF2	HTA11_411_2000001011	Human	Colorectum	SER	5.52e-07	7.20e-01	-0.2602
10204	NUTF2	HTA11_696_2000001011	Human	Colorectum	AD	8.02e-04	2.83e-01	-0.1464
10204	NUTF2	HTA11_866_2000001011	Human	Colorectum	AD	1.61e-05	2.54e-01	-0.1001
10204	NUTF2	HTA11_1391_2000001011	Human	Colorectum	AD	2.86e-08	3.99e-01	-0.059
10204	NUTF2	HTA11_866_3004761011	Human	Colorectum	AD	1.69e-13	4.69e-01	0.096
10204	NUTF2	HTA11_10623_2000001011	Human	Colorectum	AD	1.52e-02	2.81e-01	-0.0177
10204	NUTF2	HTA11_10711_2000001011	Human	Colorectum	AD	3.87e-02	2.31e-01	0.0338
10204	NUTF2	HTA11_7696_3000711011	Human	Colorectum	AD	3.31e-04	2.22e-01	0.0674
10204	NUTF2	HTA11_6818_2000001021	Human	Colorectum	AD	2.49e-05	3.85e-01	0.0588
10204	NUTF2	HTA11_99999970781_79442	Human	Colorectum	MSS	1.19e-11	3.63e-01	0.294
10204	NUTF2	HTA11_99999965062_69753	Human	Colorectum	MSI-H	2.21e-05	8.72e-01	0.3487
10204	NUTF2	HTA11_99999965104_69814	Human	Colorectum	MSS	6.41e-14	6.50e-01	0.281
10204	NUTF2	HTA11_99999971662_82457	Human	Colorectum	MSS	5.52e-23	7.05e-01	0.3859
10204	NUTF2	HTA11_99999973899_84307	Human	Colorectum	MSS	1.42e-04	3.45e-01	0.2585
10204	NUTF2	HTA11_99999974143_84620	Human	Colorectum	MSS	5.05e-06	2.86e-01	0.3005
10204	NUTF2	LZE2D	Human	Esophagus	HGIN	5.37e-04	2.02e-01	0.0642

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal 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
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:1904951111	Esophagus	ESCC	positive regulation of establishment of protein localization	216/8552	319/18723	1.01e-15	6.86e-14	216
GO:0046822110	Esophagus	ESCC	regulation of nucleocytoplasmic transport	88/8552	106/18723	1.88e-15	1.19e-13	88
GO:009031617	Esophagus	ESCC	positive regulation of intracellular protein transport	122/8552	160/18723	2.45e-15	1.49e-13	122
GO:001703818	Esophagus	ESCC	protein import	149/8552	206/18723	5.90e-15	3.31e-13	149
GO:0051222111	Esophagus	ESCC	positive regulation of protein transport	204/8552	303/18723	1.56e-14	8.38e-13	204
GO:190018018	Esophagus	ESCC	regulation of protein localization to nucleus	102/8552	136/18723	2.84e-12	1.13e-10	102
GO:190018217	Esophagus	ESCC	positive regulation of protein localization to nucleus	70/8552	87/18723	2.63e-11	8.99e-10	70
GO:004682417	Esophagus	ESCC	positive regulation of nucleocytoplasmic transport	52/8552	62/18723	5.40e-10	1.38e-08	52
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:000661117	Esophagus	ESCC	protein export from nucleus	48/8552	57/18723	1.92e-09	4.39e-08	48
GO:190458914	Esophagus	ESCC	regulation of protein import	49/8552	63/18723	1.91e-07	2.97e-06	49
GO:190459116	Esophagus	ESCC	positive regulation of protein import	36/8552	43/18723	2.90e-07	4.20e-06	36
GO:004230614	Esophagus	ESCC	regulation of protein import into nucleus	46/8552	60/18723	9.55e-07	1.21e-05	46
GO:004230715	Esophagus	ESCC	positive regulation of protein import into nucleus	34/8552	41/18723	9.84e-07	1.24e-05	34
GO:007259412	Liver	Cirrhotic	establishment of protein localization to organelle	189/4634	422/18723	1.01e-19	2.45e-17	189
GO:003238611	Liver	Cirrhotic	regulation of intracellular transport	147/4634	337/18723	1.84e-14	1.72e-12	147
GO:003315711	Liver	Cirrhotic	regulation of intracellular protein transport	108/4634	229/18723	1.23e-13	1.04e-11	108
GO:190382912	Liver	Cirrhotic	positive regulation of cellular protein localization	123/4634	276/18723	4.06e-13	3.22e-11	123
GO:190495112	Liver	Cirrhotic	positive regulation of establishment of protein localization	135/4634	319/18723	3.20e-12	2.28e-10	135

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

NUTF2

SNV

Missense_Mutation

c.209C>T

p.Ala70Val

p.A70V

P61970

protein_coding

tolerated(0.26)

benign(0.048)

TCGA-AR-A1AV-01

Breast

breast invasive carcinoma

Male

>=65

I/II

Chemotherapy

cytoxan

NUTF2

insertion

In_Frame_Ins

novel

c.172-1_172insGTGCGATTTCGGCTCGCTACAAACCGCCGCCTCCTGGGTTCA

p.Ser57_Ser58insValArgPheArgLeuAlaThrAsnArgArgLeuLeuGlySer

p.S57_S58insVRFRLATNRRLLGS

P61970

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NUTF2

deletion

Frame_Shift_Del

novel

c.267delT

p.Lys90ArgfsTer16

p.K90Rfs*16

P61970

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

NUTF2

SNV

Missense_Mutation

c.110C>T

p.Ser37Leu

p.S37L

P61970

protein_coding

deleterious(0)

probably_damaging(0.941)

TCGA-C5-A1M6-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NUTF2

SNV

Missense_Mutation

novel

c.27N>C

p.Gln9His

p.Q9H

P61970

protein_coding

tolerated(0.15)

benign(0.003)

TCGA-IR-A3LI-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NUTF2

SNV

Missense_Mutation

novel

c.119N>T

p.Thr40Met

p.T40M

P61970

protein_coding

deleterious(0.03)

possibly_damaging(0.596)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

NUTF2

SNV

Missense_Mutation

c.209C>T

p.Ala70Val

p.A70V

P61970

protein_coding

tolerated(0.26)

benign(0.048)

TCGA-AJ-A3EL-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NUTF2

SNV

Missense_Mutation

rs780123868

c.107C>T

p.Ala36Val

p.A36V

P61970

protein_coding

tolerated(0.3)

benign(0.007)

TCGA-D1-A103-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

NUTF2

SNV

Missense_Mutation

novel

c.73N>T

p.Asp25Tyr

p.D25Y

P61970

protein_coding

deleterious(0)

probably_damaging(0.975)

TCGA-EO-A22U-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

NUTF2

SNV

Missense_Mutation

novel

c.263A>T

p.Gln88Leu

p.Q88L

P61970

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-DD-AACZ-01

Liver

liver hepatocellular carcinoma

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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