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: XPO1

Gene summary for XPO1

Gene summary.

Gene information	Species	Human
	Gene symbol	XPO1
	Gene ID	7514
	Gene name	exportin 1
	Gene Alias	CRM-1
	Cytomap	2p15
	Gene Type	protein-coding
	GO ID	GO:0000054
	UniProtAcc	B3KWD0

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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
7514	XPO1	CA_HPV_1	Human	Cervix	CC	1.39e-05	1.52e-01	0.0264
7514	XPO1	CCI_1	Human	Cervix	CC	2.45e-03	1.19e+00	0.528
7514	XPO1	CCI_2	Human	Cervix	CC	1.46e-08	1.47e+00	0.5249
7514	XPO1	CCI_3	Human	Cervix	CC	1.50e-13	1.12e+00	0.516
7514	XPO1	AEH-subject1	Human	Endometrium	AEH	9.37e-05	-1.87e-02	-0.3059
7514	XPO1	AEH-subject3	Human	Endometrium	AEH	9.04e-07	-4.58e-02	-0.2576
7514	XPO1	AEH-subject4	Human	Endometrium	AEH	2.92e-02	2.20e-01	-0.2657
7514	XPO1	EEC-subject1	Human	Endometrium	EEC	1.38e-10	1.88e-01	-0.2682
7514	XPO1	EEC-subject3	Human	Endometrium	EEC	1.61e-10	-1.01e-01	-0.2525
7514	XPO1	EEC-subject4	Human	Endometrium	EEC	4.02e-04	1.32e-03	-0.2571
7514	XPO1	GSM5276934	Human	Endometrium	EEC	3.98e-10	-2.65e-01	-0.0913
7514	XPO1	GSM5276937	Human	Endometrium	EEC	6.70e-03	-2.13e-01	-0.0897
7514	XPO1	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	1.61e-19	1.49e-01	-0.1869
7514	XPO1	GSM6177620_NYU_UCEC1_lib2_lib2	Human	Endometrium	EEC	1.82e-21	3.29e-02	-0.1875
7514	XPO1	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	8.79e-21	-5.92e-02	-0.1883
7514	XPO1	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	7.40e-21	1.89e-01	-0.1934
7514	XPO1	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	5.67e-38	1.42e-01	-0.1917
7514	XPO1	GSM6177622_NYU_UCEC3_lib2_lib2	Human	Endometrium	EEC	8.07e-26	1.89e-01	-0.1916
7514	XPO1	GSM6177623_NYU_UCEC3_Vis	Human	Endometrium	EEC	5.11e-16	5.11e-01	-0.1269
7514	XPO1	LZE2T	Human	Esophagus	ESCC	4.97e-07	1.08e+00	0.082

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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
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:005065811	Liver	HCC	RNA transport	118/7958	163/18723	8.30e-15	5.60e-13	118
GO:001593111	Liver	HCC	nucleobase-containing compound transport	150/7958	222/18723	3.17e-14	2.03e-12	150
GO:003243422	Liver	HCC	regulation of proteasomal ubiquitin-dependent protein catabolic process	100/7958	134/18723	3.67e-14	2.32e-12	100
GO:005102811	Liver	HCC	mRNA transport	97/7958	130/18723	9.00e-14	5.23e-12	97
GO:004682221	Liver	HCC	regulation of nucleocytoplasmic transport	81/7958	106/18723	1.11e-12	5.52e-11	81
GO:005165621	Liver	HCC	establishment of organelle localization	226/7958	390/18723	4.15e-10	1.34e-08	226
GO:00711661	Liver	HCC	ribonucleoprotein complex localization	59/7958	77/18723	1.09e-09	3.30e-08	59
GO:00714261	Liver	HCC	ribonucleoprotein complex export from nucleus	58/7958	76/18723	1.98e-09	5.63e-08	58
GO:000941022	Liver	HCC	response to xenobiotic stimulus	248/7958	462/18723	6.47e-07	1.02e-05	248
GO:00315031	Liver	HCC	protein-containing complex localization	129/7958	220/18723	9.38e-07	1.42e-05	129
GO:000661112	Liver	HCC	protein export from nucleus	42/7958	57/18723	1.75e-06	2.45e-05	42
GO:004682512	Liver	HCC	regulation of protein export from nucleus	24/7958	30/18723	3.08e-05	3.16e-04	24
GO:0031023	Liver	HCC	microtubule organizing center organization	82/7958	143/18723	2.38e-04	1.79e-03	82
GO:0007098	Liver	HCC	centrosome cycle	75/7958	130/18723	3.33e-04	2.34e-03	75
GO:00000544	Liver	HCC	ribosomal subunit export from nucleus	12/7958	14/18723	1.17e-03	6.54e-03	12
GO:00337504	Liver	HCC	ribosome localization	12/7958	14/18723	1.17e-03	6.54e-03	12
GO:00714282	Liver	HCC	rRNA-containing ribonucleoprotein complex export from nucleus	12/7958	15/18723	3.56e-03	1.59e-02	12
GO:0032886	Liver	HCC	regulation of microtubule-based process	123/7958	240/18723	3.69e-03	1.64e-02	123
GO:00466052	Liver	HCC	regulation of centrosome cycle	30/7958	49/18723	6.31e-03	2.57e-02	30
GO:002261320	Oral cavity	OSCC	ribonucleoprotein complex biogenesis	333/7305	463/18723	8.28e-48	5.24e-44	333

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0516620	Cervix	CC	Human T-cell leukemia virus 1 infection	61/1267	222/8465	8.13e-07	7.98e-06	4.72e-06	61
hsa0516414	Cervix	CC	Influenza A	43/1267	171/8465	3.03e-04	1.64e-03	9.68e-04	43
hsa05166110	Cervix	CC	Human T-cell leukemia virus 1 infection	61/1267	222/8465	8.13e-07	7.98e-06	4.72e-06	61
hsa0516415	Cervix	CC	Influenza A	43/1267	171/8465	3.03e-04	1.64e-03	9.68e-04	43
hsa0516626	Endometrium	AEH	Human T-cell leukemia virus 1 infection	50/1197	222/8465	4.30e-04	3.11e-03	2.27e-03	50
hsa05166111	Endometrium	AEH	Human T-cell leukemia virus 1 infection	50/1197	222/8465	4.30e-04	3.11e-03	2.27e-03	50
hsa0516627	Endometrium	EEC	Human T-cell leukemia virus 1 infection	52/1237	222/8465	2.73e-04	2.36e-03	1.76e-03	52
hsa0516636	Endometrium	EEC	Human T-cell leukemia virus 1 infection	52/1237	222/8465	2.73e-04	2.36e-03	1.76e-03	52
hsa030137	Esophagus	HGIN	Nucleocytoplasmic transport	31/1383	108/8465	8.29e-04	7.95e-03	6.31e-03	31
hsa0516639	Esophagus	HGIN	Human T-cell leukemia virus 1 infection	51/1383	222/8465	5.84e-03	4.05e-02	3.22e-02	51
hsa0301312	Esophagus	HGIN	Nucleocytoplasmic transport	31/1383	108/8465	8.29e-04	7.95e-03	6.31e-03	31
hsa05166114	Esophagus	HGIN	Human T-cell leukemia virus 1 infection	51/1383	222/8465	5.84e-03	4.05e-02	3.22e-02	51
hsa05166211	Esophagus	ESCC	Human T-cell leukemia virus 1 infection	164/4205	222/8465	8.13e-14	2.09e-12	1.07e-12	164
hsa0301321	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa032509	Esophagus	ESCC	Viral life cycle - HIV-1	54/4205	63/8465	2.01e-09	2.17e-08	1.11e-08	54
hsa0516425	Esophagus	ESCC	Influenza A	122/4205	171/8465	5.01e-09	4.79e-08	2.45e-08	122
hsa05166310	Esophagus	ESCC	Human T-cell leukemia virus 1 infection	164/4205	222/8465	8.13e-14	2.09e-12	1.07e-12	164
hsa0301331	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa0325014	Esophagus	ESCC	Viral life cycle - HIV-1	54/4205	63/8465	2.01e-09	2.17e-08	1.11e-08	54
hsa0516435	Esophagus	ESCC	Influenza A	122/4205	171/8465	5.01e-09	4.79e-08	2.45e-08	122

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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

XPO1

SNV

Missense_Mutation

c.1508N>G

p.Ser503Cys

p.S503C

O14980

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

XPO1

SNV

Missense_Mutation

c.1293N>C

p.Leu431Phe

p.L431F

O14980

protein_coding

deleterious(0)

possibly_damaging(0.693)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

XPO1

SNV

Missense_Mutation

rs769916613

c.40N>T

p.Arg14Cys

p.R14C

O14980

protein_coding

deleterious(0.03)

benign(0.255)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

XPO1

SNV

Missense_Mutation

novel

c.2534N>T

p.Arg845Ile

p.R845I

O14980

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

XPO1

SNV

Missense_Mutation

c.2246N>A

p.Arg749Gln

p.R749Q

O14980

protein_coding

deleterious(0)

probably_damaging(0.922)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

XPO1

SNV

Missense_Mutation

novel

c.1537N>A

p.Glu513Lys

p.E513K

O14980

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

XPO1

SNV

Missense_Mutation

c.1943N>T

p.Thr648Ile

p.T648I

O14980

protein_coding

tolerated(0.22)

benign(0)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

XPO1

SNV

Missense_Mutation

c.3033N>G

p.Phe1011Leu

p.F1011L

O14980

protein_coding

deleterious(0.02)

benign(0.033)

TCGA-BH-A0HP-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

XPO1

SNV

Missense_Mutation

c.1711N>A

p.Glu571Lys

p.E571K

O14980

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-BH-A18F-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

XPO1

SNV

Missense_Mutation

c.1711N>A

p.Glu571Lys

p.E571K

O14980

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-BH-A203-01

Breast

breast invasive 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
7514	XPO1	CLINICALLY ACTIONABLE, KINASE	inhibitor	CHEMBL3545185	SELINEXOR
7514	XPO1	CLINICALLY ACTIONABLE, KINASE		Selinexor oral
7514	XPO1	CLINICALLY ACTIONABLE, KINASE		SL-801	CBS-9106
7514	XPO1	CLINICALLY ACTIONABLE, KINASE		KOS-1815		24631834
7514	XPO1	CLINICALLY ACTIONABLE, KINASE		Eltanexor oral
7514	XPO1	CLINICALLY ACTIONABLE, KINASE		LEPTOMYCIN B	LEPTOMYCIN B	18835718
7514	XPO1	CLINICALLY ACTIONABLE, KINASE	inhibitor	375973225	ELTANEXOR
7514	XPO1	CLINICALLY ACTIONABLE, KINASE		KPT-330	SELINEXOR	24631834
7514	XPO1	CLINICALLY ACTIONABLE, KINASE		isoniazid	ISONIAZID	22341855,29036176
7514	XPO1	CLINICALLY ACTIONABLE, KINASE		GONIOTHALAMIN	GONIOTHALAMIN	20381347

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