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: NFX1

Gene summary for NFX1

Gene summary.

Gene information	Species	Human
	Gene symbol	NFX1
	Gene ID	4799
	Gene name	nuclear transcription factor, X-box binding 1
	Gene Alias	NFX2
	Cytomap	9p13.3
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	Q12986

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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
4799	NFX1	CCI_1	Human	Cervix	CC	3.69e-02	5.62e-01	0.528
4799	NFX1	CCI_2	Human	Cervix	CC	4.46e-12	1.15e+00	0.5249
4799	NFX1	CCI_3	Human	Cervix	CC	1.37e-05	6.62e-01	0.516
4799	NFX1	HTA11_347_2000001011	Human	Colorectum	AD	2.48e-06	4.31e-01	-0.1954
4799	NFX1	HTA11_99999965062_69753	Human	Colorectum	MSI-H	6.79e-06	1.17e+00	0.3487
4799	NFX1	A001-C-207	Human	Colorectum	FAP	1.27e-03	-2.59e-01	0.1278
4799	NFX1	A015-C-203	Human	Colorectum	FAP	1.07e-19	-3.44e-01	-0.1294
4799	NFX1	A015-C-204	Human	Colorectum	FAP	2.21e-06	-3.37e-01	-0.0228
4799	NFX1	A014-C-040	Human	Colorectum	FAP	3.20e-03	-2.80e-01	-0.1184
4799	NFX1	A002-C-201	Human	Colorectum	FAP	2.58e-13	-3.39e-01	0.0324
4799	NFX1	A002-C-203	Human	Colorectum	FAP	1.30e-03	-1.68e-01	0.2786
4799	NFX1	A001-C-119	Human	Colorectum	FAP	5.19e-08	-4.12e-01	-0.1557
4799	NFX1	A001-C-108	Human	Colorectum	FAP	2.51e-10	-2.44e-01	-0.0272
4799	NFX1	A002-C-205	Human	Colorectum	FAP	8.14e-19	-3.81e-01	-0.1236
4799	NFX1	A001-C-104	Human	Colorectum	FAP	3.51e-02	-2.39e-01	0.0184
4799	NFX1	A015-C-005	Human	Colorectum	FAP	4.05e-02	-1.75e-01	-0.0336
4799	NFX1	A015-C-006	Human	Colorectum	FAP	1.27e-12	-3.33e-01	-0.0994
4799	NFX1	A015-C-106	Human	Colorectum	FAP	2.35e-08	-2.37e-01	-0.0511
4799	NFX1	A002-C-114	Human	Colorectum	FAP	2.12e-17	-4.66e-01	-0.1561
4799	NFX1	A015-C-104	Human	Colorectum	FAP	2.27e-19	-2.81e-01	-0.1899

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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
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
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:00518656	Cervix	CC	protein autoubiquitination	17/2311	73/18723	6.71e-03	3.70e-02	17
GO:0006325	Colorectum	AD	chromatin organization	119/3918	409/18723	4.85e-05	8.33e-04	119
GO:0051865	Colorectum	AD	protein autoubiquitination	28/3918	73/18723	4.87e-04	5.30e-03	28
GO:00063251	Colorectum	SER	chromatin organization	89/2897	409/18723	4.15e-04	6.17e-03	89
GO:00063252	Colorectum	MSS	chromatin organization	107/3467	409/18723	7.22e-05	1.21e-03	107
GO:00518652	Colorectum	FAP	protein autoubiquitination	22/2622	73/18723	2.88e-04	3.77e-03	22
GO:00518653	Colorectum	CRC	protein autoubiquitination	18/2078	73/18723	8.33e-04	1.04e-02	18
GO:000632517	Esophagus	ESCC	chromatin organization	240/8552	409/18723	6.52e-08	1.14e-06	240
GO:00400295	Esophagus	ESCC	regulation of gene expression, epigenetic	74/8552	105/18723	2.24e-07	3.42e-06	74
GO:00518658	Esophagus	ESCC	protein autoubiquitination	47/8552	73/18723	9.72e-04	4.93e-03	47
GO:00708281	Esophagus	ESCC	heterochromatin organization	31/8552	46/18723	2.42e-03	1.06e-02	31
GO:0045814	Esophagus	ESCC	negative regulation of gene expression, epigenetic	32/8552	50/18723	6.90e-03	2.52e-02	32
GO:000632511	Liver	HCC	chromatin organization	206/7958	409/18723	7.23e-04	4.41e-03	206
GO:0040029	Liver	HCC	regulation of gene expression, epigenetic	61/7958	105/18723	9.02e-04	5.31e-03	61
GO:00518654	Liver	HCC	protein autoubiquitination	42/7958	73/18723	6.78e-03	2.73e-02	42
GO:00400294	Oral cavity	OSCC	regulation of gene expression, epigenetic	59/7305	105/18723	2.62e-04	1.68e-03	59
GO:000632510	Oral cavity	OSCC	chromatin organization	190/7305	409/18723	1.17e-03	5.97e-03	190
GO:00518657	Oral cavity	OSCC	protein autoubiquitination	40/7305	73/18723	4.45e-03	1.79e-02	40
GO:004002911	Oral cavity	LP	regulation of gene expression, epigenetic	39/4623	105/18723	3.00e-03	2.05e-02	39
GO:005186512	Oral cavity	LP	protein autoubiquitination	29/4623	73/18723	3.20e-03	2.18e-02	29

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa051657	Cervix	CC	Human papillomavirus infection	74/1267	331/8465	1.70e-04	1.02e-03	6.03e-04	74
hsa0516512	Cervix	CC	Human papillomavirus infection	74/1267	331/8465	1.70e-04	1.02e-03	6.03e-04	74
hsa0516510	Esophagus	ESCC	Human papillomavirus infection	215/4205	331/8465	7.86e-09	7.12e-08	3.65e-08	215
hsa0516515	Esophagus	ESCC	Human papillomavirus infection	215/4205	331/8465	7.86e-09	7.12e-08	3.65e-08	215
hsa05165	Liver	Cirrhotic	Human papillomavirus infection	124/2530	331/8465	1.55e-03	7.83e-03	4.83e-03	124
hsa051651	Liver	Cirrhotic	Human papillomavirus infection	124/2530	331/8465	1.55e-03	7.83e-03	4.83e-03	124
hsa051652	Liver	HCC	Human papillomavirus infection	188/4020	331/8465	3.34e-04	1.49e-03	8.29e-04	188
hsa051653	Liver	HCC	Human papillomavirus infection	188/4020	331/8465	3.34e-04	1.49e-03	8.29e-04	188
hsa051659	Oral cavity	OSCC	Human papillomavirus infection	200/3704	331/8465	3.83e-10	4.93e-09	2.51e-09	200
hsa0516514	Oral cavity	OSCC	Human papillomavirus infection	200/3704	331/8465	3.83e-10	4.93e-09	2.51e-09	200
hsa0516523	Oral cavity	LP	Human papillomavirus infection	121/2418	331/8465	8.00e-04	3.86e-03	2.49e-03	121
hsa0516533	Oral cavity	LP	Human papillomavirus infection	121/2418	331/8465	8.00e-04	3.86e-03	2.49e-03	121
hsa0516541	Oral cavity	EOLP	Human papillomavirus infection	79/1218	331/8465	1.96e-06	1.63e-05	9.60e-06	79
hsa0516551	Oral cavity	EOLP	Human papillomavirus infection	79/1218	331/8465	1.96e-06	1.63e-05	9.60e-06	79
hsa0516561	Oral cavity	NEOLP	Human papillomavirus infection	90/1112	331/8465	2.75e-12	1.75e-10	1.10e-10	90
hsa0516571	Oral cavity	NEOLP	Human papillomavirus infection	90/1112	331/8465	2.75e-12	1.75e-10	1.10e-10	90

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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

NFX1

SNV

Missense_Mutation

novel

c.2790N>T

p.Glu930Asp

p.E930D

Q12986

protein_coding

tolerated(0.49)

benign(0.007)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NFX1

SNV

Missense_Mutation

rs199721480

c.1756N>T

p.Arg586Trp

p.R586W

Q12986

protein_coding

deleterious(0.02)

probably_damaging(0.978)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

NFX1

SNV

Missense_Mutation

c.3029N>T

p.Ala1010Val

p.A1010V

Q12986

protein_coding

tolerated(0.1)

benign(0.212)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NFX1

SNV

Missense_Mutation

novel

c.1387N>G

p.Pro463Ala

p.P463A

Q12986

protein_coding

deleterious(0.01)

probably_damaging(0.968)

TCGA-BH-A8FZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NFX1

SNV

Missense_Mutation

c.1911N>G

p.Phe637Leu

p.F637L

Q12986

protein_coding

tolerated(0.54)

benign(0.009)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

NFX1

SNV

Missense_Mutation

c.2948G>T

p.Ser983Ile

p.S983I

Q12986

protein_coding

deleterious(0)

benign(0.184)

TCGA-D8-A1JM-01

Breast

breast invasive carcinoma

Female

<65

I/II

ChemotherapyHormone Therapy

doxorubicine

NFX1

SNV

Missense_Mutation

c.568N>C

p.Cys190Arg

p.C190R

Q12986

protein_coding

tolerated_low_confidence(0.35)

benign(0.014)

TCGA-EW-A1IZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxotere

NFX1

insertion

Frame_Shift_Ins

novel

c.3258_3259insTGTTTCTCTGCTTGTGTGTCTGTAT

p.Pro1087CysfsTer25

p.P1087Cfs*25

Q12986

protein_coding

TCGA-A2-A04Y-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

NFX1

insertion

Nonsense_Mutation

novel

c.1032_1033insCTGTTTTGAAAGAAGACCACATGGAACCTGATGATTGATATCCCT

p.Thr344_Gly345insLeuPheTerLysLysThrThrTrpAsnLeuMetIleAspIlePro

p.T344_G345insLF*KKTTWNLMIDIP

Q12986

protein_coding

TCGA-A8-A0A1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

NFX1

insertion

Frame_Shift_Ins

novel

c.1149_1150insGCTTATGGTAGGCACCAAGAATATCTTTGTT

p.Asn384AlafsTer11

p.N384Afs*11

Q12986

protein_coding

TCGA-AO-A03R-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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