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: KPNA2

Gene summary for KPNA2

Gene summary.

Gene information	Species	Human
	Gene symbol	KPNA2
	Gene ID	3838
	Gene name	karyopherin subunit alpha 2
	Gene Alias	IPOA1
	Cytomap	17q24.2
	Gene Type	protein-coding
	GO ID	GO:0000018
	UniProtAcc	P52292

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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
3838	KPNA2	HTA11_1391_2000001011	Human	Colorectum	AD	1.66e-05	5.16e-01	-0.059
3838	KPNA2	HTA11_99999970781_79442	Human	Colorectum	MSS	4.63e-10	3.58e-01	0.294
3838	KPNA2	HTA11_99999971662_82457	Human	Colorectum	MSS	3.94e-08	2.89e-01	0.3859
3838	KPNA2	LZE4T	Human	Esophagus	ESCC	7.93e-11	4.98e-01	0.0811
3838	KPNA2	LZE5T	Human	Esophagus	ESCC	6.08e-03	8.92e-02	0.0514
3838	KPNA2	LZE7T	Human	Esophagus	ESCC	3.91e-05	5.46e-01	0.0667
3838	KPNA2	LZE8T	Human	Esophagus	ESCC	9.27e-09	6.69e-02	0.067
3838	KPNA2	LZE22D1	Human	Esophagus	HGIN	2.85e-03	-1.56e-01	0.0595
3838	KPNA2	LZE24T	Human	Esophagus	ESCC	2.84e-07	4.56e-01	0.0596
3838	KPNA2	LZE6T	Human	Esophagus	ESCC	2.30e-02	5.05e-01	0.0845
3838	KPNA2	P1T-E	Human	Esophagus	ESCC	2.15e-11	3.56e-01	0.0875
3838	KPNA2	P2T-E	Human	Esophagus	ESCC	4.87e-16	7.58e-01	0.1177
3838	KPNA2	P4T-E	Human	Esophagus	ESCC	2.83e-10	5.46e-01	0.1323
3838	KPNA2	P5T-E	Human	Esophagus	ESCC	2.09e-47	1.76e+00	0.1327
3838	KPNA2	P8T-E	Human	Esophagus	ESCC	2.34e-06	2.45e-01	0.0889
3838	KPNA2	P9T-E	Human	Esophagus	ESCC	5.70e-11	6.08e-01	0.1131
3838	KPNA2	P10T-E	Human	Esophagus	ESCC	3.89e-09	4.06e-01	0.116
3838	KPNA2	P11T-E	Human	Esophagus	ESCC	2.96e-14	8.62e-01	0.1426
3838	KPNA2	P12T-E	Human	Esophagus	ESCC	3.92e-31	1.01e+00	0.1122
3838	KPNA2	P15T-E	Human	Esophagus	ESCC	1.51e-17	6.71e-01	0.1149

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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
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ

∗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:0016032	Colorectum	AD	viral process	168/3918	415/18723	4.67e-20	3.66e-17	168
GO:0019058	Colorectum	AD	viral life cycle	119/3918	317/18723	6.18e-12	8.23e-10	119
GO:0072594	Colorectum	AD	establishment of protein localization to organelle	148/3918	422/18723	7.95e-12	1.04e-09	148
GO:0006913	Colorectum	AD	nucleocytoplasmic transport	102/3918	301/18723	1.00e-07	4.85e-06	102
GO:0051169	Colorectum	AD	nuclear transport	102/3918	301/18723	1.00e-07	4.85e-06	102
GO:0051052	Colorectum	AD	regulation of DNA metabolic process	116/3918	359/18723	2.47e-07	1.00e-05	116
GO:0048524	Colorectum	AD	positive regulation of viral process	31/3918	65/18723	1.33e-06	4.23e-05	31
GO:0034504	Colorectum	AD	protein localization to nucleus	94/3918	290/18723	2.83e-06	8.09e-05	94
GO:0050792	Colorectum	AD	regulation of viral process	59/3918	164/18723	5.95e-06	1.52e-04	59
GO:0017038	Colorectum	AD	protein import	67/3918	206/18723	6.34e-05	1.05e-03	67
GO:1903900	Colorectum	AD	regulation of viral life cycle	51/3918	148/18723	9.01e-05	1.38e-03	51
GO:0051170	Colorectum	AD	import into nucleus	53/3918	159/18723	1.76e-04	2.38e-03	53
GO:0006606	Colorectum	AD	protein import into nucleus	51/3918	155/18723	3.29e-04	3.86e-03	51
GO:1903902	Colorectum	AD	positive regulation of viral life cycle	14/3918	29/18723	9.40e-04	8.92e-03	14
GO:00160322	Colorectum	MSS	viral process	157/3467	415/18723	7.94e-21	6.19e-18	157
GO:00725942	Colorectum	MSS	establishment of protein localization to organelle	139/3467	422/18723	5.75e-13	1.12e-10	139
GO:00190582	Colorectum	MSS	viral life cycle	111/3467	317/18723	1.65e-12	2.95e-10	111
GO:00069132	Colorectum	MSS	nucleocytoplasmic transport	99/3467	301/18723	1.35e-09	1.03e-07	99
GO:00511692	Colorectum	MSS	nuclear transport	99/3467	301/18723	1.35e-09	1.03e-07	99
GO:00345042	Colorectum	MSS	protein localization to nucleus	92/3467	290/18723	3.66e-08	1.98e-06	92

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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
hsa0516420	Esophagus	HGIN	Influenza A	42/1383	171/8465	3.41e-03	2.54e-02	2.02e-02	42
hsa0301312	Esophagus	HGIN	Nucleocytoplasmic transport	31/1383	108/8465	8.29e-04	7.95e-03	6.31e-03	31
hsa05164110	Esophagus	HGIN	Influenza A	42/1383	171/8465	3.41e-03	2.54e-02	2.02e-02	42
hsa0301321	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa0516425	Esophagus	ESCC	Influenza A	122/4205	171/8465	5.01e-09	4.79e-08	2.45e-08	122
hsa0301331	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa0516435	Esophagus	ESCC	Influenza A	122/4205	171/8465	5.01e-09	4.79e-08	2.45e-08	122
hsa03013	Liver	HCC	Nucleocytoplasmic transport	81/4020	108/8465	4.28e-09	6.83e-08	3.80e-08	81
hsa0516421	Liver	HCC	Influenza A	101/4020	171/8465	1.41e-03	5.07e-03	2.82e-03	101
hsa030131	Liver	HCC	Nucleocytoplasmic transport	81/4020	108/8465	4.28e-09	6.83e-08	3.80e-08	81
hsa0516431	Liver	HCC	Influenza A	101/4020	171/8465	1.41e-03	5.07e-03	2.82e-03	101
hsa030136	Oral cavity	OSCC	Nucleocytoplasmic transport	82/3704	108/8465	7.93e-12	1.33e-10	6.77e-11	82
hsa0516418	Oral cavity	OSCC	Influenza A	116/3704	171/8465	1.23e-10	1.78e-09	9.08e-10	116
hsa0301311	Oral cavity	OSCC	Nucleocytoplasmic transport	82/3704	108/8465	7.93e-12	1.33e-10	6.77e-11	82
hsa0516419	Oral cavity	OSCC	Influenza A	116/3704	171/8465	1.23e-10	1.78e-09	9.08e-10	116
hsa0516442	Oral cavity	EOLP	Influenza A	58/1218	171/8465	7.01e-11	3.23e-09	1.91e-09	58
hsa030134	Oral cavity	EOLP	Nucleocytoplasmic transport	34/1218	108/8465	4.24e-06	2.91e-05	1.72e-05	34
hsa0516452	Oral cavity	EOLP	Influenza A	58/1218	171/8465	7.01e-11	3.23e-09	1.91e-09	58
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

KPNA2

SNV

Missense_Mutation

novel

c.680N>A

p.Arg227His

p.R227H

P52292

protein_coding

deleterious(0.01)

benign(0.286)

TCGA-A7-A0DB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

KPNA2

SNV

Missense_Mutation

c.235N>A

p.Asp79Asn

p.D79N

P52292

protein_coding

tolerated(0.06)

benign(0.026)

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

KPNA2

SNV

Missense_Mutation

rs782272780

c.85C>T

p.Arg29Cys

p.R29C

P52292

protein_coding

deleterious(0.02)

probably_damaging(0.983)

TCGA-AO-A12F-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

paclitaxel

KPNA2

SNV

Missense_Mutation

c.1144N>T

p.Leu382Phe

p.L382F

P52292

protein_coding

deleterious(0.02)

probably_damaging(0.989)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

KPNA2

SNV

Missense_Mutation

rs782787344

c.1097N>A

p.Arg366His

p.R366H

P52292

protein_coding

tolerated(0.17)

benign(0.003)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

KPNA2

SNV

Missense_Mutation

c.1124A>G

p.Asn375Ser

p.N375S

P52292

protein_coding

tolerated(0.36)

benign(0)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

KPNA2

insertion

Frame_Shift_Ins

novel

c.744_745insCATGCCTGTAATCCCAGCACTTTGGGAGGCCAAGGGGTCG

p.Val249HisfsTer15

p.V249Hfs*15

P52292

protein_coding

TCGA-A2-A0CT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

KPNA2

SNV

Missense_Mutation

c.878N>T

p.Gly293Val

p.G293V

P52292

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-BI-A0VS-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

KPNA2

SNV

Missense_Mutation

novel

c.952N>C

p.Gly318Arg

p.G318R

P52292

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-C5-A1BQ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

KPNA2

SNV

Missense_Mutation

novel

c.952N>C

p.Gly318Arg

p.G318R

P52292

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-C5-A3HL-01

Cervix

cervical & endocervical cancer

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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