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: IPO7

Gene summary for IPO7

Gene summary.

Gene information	Species	Human
	Gene symbol	IPO7
	Gene ID	10527
	Gene name	importin 7
	Gene Alias	Imp7
	Cytomap	11p15.4
	Gene Type	protein-coding
	GO ID	GO:0000079
	UniProtAcc	B3KNG9

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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
10527	IPO7	LZE4T	Human	Esophagus	ESCC	6.97e-06	1.88e-01	0.0811
10527	IPO7	LZE7T	Human	Esophagus	ESCC	1.85e-03	4.86e-01	0.0667
10527	IPO7	LZE8T	Human	Esophagus	ESCC	8.96e-13	1.14e-01	0.067
10527	IPO7	LZE20T	Human	Esophagus	ESCC	2.16e-12	-2.00e-01	0.0662
10527	IPO7	LZE22D1	Human	Esophagus	HGIN	5.92e-09	-2.15e-01	0.0595
10527	IPO7	LZE22T	Human	Esophagus	ESCC	3.15e-03	-8.21e-02	0.068
10527	IPO7	LZE24T	Human	Esophagus	ESCC	1.07e-08	5.09e-01	0.0596
10527	IPO7	LZE21T	Human	Esophagus	ESCC	8.33e-05	-8.41e-02	0.0655
10527	IPO7	P1T-E	Human	Esophagus	ESCC	2.69e-03	-1.23e-01	0.0875
10527	IPO7	P2T-E	Human	Esophagus	ESCC	7.40e-20	4.36e-01	0.1177
10527	IPO7	P4T-E	Human	Esophagus	ESCC	4.56e-10	1.04e-01	0.1323
10527	IPO7	P5T-E	Human	Esophagus	ESCC	1.69e-09	-5.97e-02	0.1327
10527	IPO7	P8T-E	Human	Esophagus	ESCC	1.75e-12	7.25e-02	0.0889
10527	IPO7	P9T-E	Human	Esophagus	ESCC	5.89e-11	2.36e-01	0.1131
10527	IPO7	P10T-E	Human	Esophagus	ESCC	5.88e-11	1.76e-01	0.116
10527	IPO7	P11T-E	Human	Esophagus	ESCC	5.06e-11	6.28e-01	0.1426
10527	IPO7	P12T-E	Human	Esophagus	ESCC	1.22e-23	-5.85e-02	0.1122
10527	IPO7	P15T-E	Human	Esophagus	ESCC	5.32e-26	8.31e-01	0.1149
10527	IPO7	P16T-E	Human	Esophagus	ESCC	8.12e-18	2.30e-01	0.1153
10527	IPO7	P17T-E	Human	Esophagus	ESCC	5.27e-04	5.47e-01	0.1278

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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
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:001703831	Oral cavity	NEOLP	protein import	42/2005	206/18723	2.98e-05	4.54e-04	42
GO:000660631	Oral cavity	NEOLP	protein import into nucleus	34/2005	155/18723	3.55e-05	5.20e-04	34
GO:007259416	Prostate	BPH	establishment of protein localization to organelle	142/3107	422/18723	4.01e-18	1.31e-15	142
GO:003450410	Prostate	BPH	protein localization to nucleus	98/3107	290/18723	4.78e-13	4.35e-11	98
GO:004593618	Prostate	BPH	negative regulation of phosphate metabolic process	124/3107	441/18723	5.95e-10	2.90e-08	124
GO:001056318	Prostate	BPH	negative regulation of phosphorus metabolic process	124/3107	442/18723	6.94e-10	3.25e-08	124
GO:000691315	Prostate	BPH	nucleocytoplasmic transport	92/3107	301/18723	1.09e-09	4.84e-08	92
GO:005116915	Prostate	BPH	nuclear transport	92/3107	301/18723	1.09e-09	4.84e-08	92
GO:004232617	Prostate	BPH	negative regulation of phosphorylation	110/3107	385/18723	2.08e-09	8.35e-08	110
GO:000193317	Prostate	BPH	negative regulation of protein phosphorylation	97/3107	342/18723	2.74e-08	8.11e-07	97
GO:005134818	Prostate	BPH	negative regulation of transferase activity	78/3107	268/18723	1.94e-07	4.29e-06	78
GO:00719009	Prostate	BPH	regulation of protein serine/threonine kinase activity	97/3107	359/18723	3.42e-07	7.23e-06	97
GO:001703810	Prostate	BPH	protein import	62/3107	206/18723	9.72e-07	1.77e-05	62
GO:000646916	Prostate	BPH	negative regulation of protein kinase activity	62/3107	212/18723	2.81e-06	4.45e-05	62
GO:003367315	Prostate	BPH	negative regulation of kinase activity	67/3107	237/18723	4.15e-06	6.25e-05	67
GO:19040292	Prostate	BPH	regulation of cyclin-dependent protein kinase activity	34/3107	98/18723	1.00e-05	1.39e-04	34
GO:00511708	Prostate	BPH	import into nucleus	48/3107	159/18723	1.42e-05	1.85e-04	48
GO:00000792	Prostate	BPH	regulation of cyclin-dependent protein serine/threonine kinase activity	32/3107	94/18723	2.79e-05	3.27e-04	32
GO:00066068	Prostate	BPH	protein import into nucleus	46/3107	155/18723	3.42e-05	3.82e-04	46
GO:00457863	Prostate	BPH	negative regulation of cell cycle	91/3107	385/18723	2.10e-04	1.71e-03	91

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa030137	Esophagus	HGIN	Nucleocytoplasmic transport	31/1383	108/8465	8.29e-04	7.95e-03	6.31e-03	31
hsa0301312	Esophagus	HGIN	Nucleocytoplasmic transport	31/1383	108/8465	8.29e-04	7.95e-03	6.31e-03	31
hsa0301321	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa0301331	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa03013	Liver	HCC	Nucleocytoplasmic transport	81/4020	108/8465	4.28e-09	6.83e-08	3.80e-08	81
hsa030131	Liver	HCC	Nucleocytoplasmic transport	81/4020	108/8465	4.28e-09	6.83e-08	3.80e-08	81
hsa030136	Oral cavity	OSCC	Nucleocytoplasmic transport	82/3704	108/8465	7.93e-12	1.33e-10	6.77e-11	82
hsa0301311	Oral cavity	OSCC	Nucleocytoplasmic transport	82/3704	108/8465	7.93e-12	1.33e-10	6.77e-11	82
hsa030132	Oral cavity	LP	Nucleocytoplasmic transport	53/2418	108/8465	4.68e-06	4.10e-05	2.64e-05	53
hsa030133	Oral cavity	LP	Nucleocytoplasmic transport	53/2418	108/8465	4.68e-06	4.10e-05	2.64e-05	53
hsa030134	Oral cavity	EOLP	Nucleocytoplasmic transport	34/1218	108/8465	4.24e-06	2.91e-05	1.72e-05	34
hsa030135	Oral cavity	EOLP	Nucleocytoplasmic transport	34/1218	108/8465	4.24e-06	2.91e-05	1.72e-05	34

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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

IPO7

SNV

Missense_Mutation

rs773555364

c.2413N>T

p.Arg805Cys

p.R805C

O95373

protein_coding

deleterious(0.04)

benign(0.006)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

IPO7

SNV

Missense_Mutation

c.2403A>T

p.Leu801Phe

p.L801F

O95373

protein_coding

deleterious(0)

probably_damaging(0.979)

TCGA-D8-A1X8-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adrimicin+cyclophosphamide

IPO7

deletion

Frame_Shift_Del

novel

c.788delN

p.Ala264ProfsTer5

p.A264Pfs*5

O95373

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

IPO7

SNV

Missense_Mutation

c.2248A>G

p.Lys750Glu

p.K750E

O95373

protein_coding

deleterious(0.01)

possibly_damaging(0.805)

TCGA-EA-A5FO-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

IPO7

SNV

Missense_Mutation

c.1564N>G

p.Gln522Glu

p.Q522E

O95373

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-EK-A2R7-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

IPO7

SNV

Missense_Mutation

c.3044G>T

p.Gly1015Val

p.G1015V

O95373

protein_coding

deleterious(0)

benign(0.156)

TCGA-IR-A3LA-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

IPO7

SNV

Missense_Mutation

novel

c.21N>G

p.Ile7Met

p.I7M

O95373

protein_coding

deleterious(0.01)

possibly_damaging(0.681)

TCGA-MA-AA3Y-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

IPO7

SNV

Missense_Mutation

novel

c.2849N>C

p.Asp950Ala

p.D950A

O95373

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-MA-AA42-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

IPO7

SNV

Missense_Mutation

c.1976C>T

p.Ala659Val

p.A659V

O95373

protein_coding

tolerated(1)

benign(0.042)

TCGA-VS-A9V4-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

IPO7

SNV

Missense_Mutation

novel

c.2411N>G

p.Leu804Arg

p.L804R

O95373

protein_coding

deleterious(0)

possibly_damaging(0.786)

TCGA-A6-3808-01

Colorectum

colon adenocarcinoma

Male

>=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
10527	IPO7	NA		MKC-1	ENMD-981693

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