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: KPNB1

Gene summary for KPNB1

Gene summary.

Gene information	Species	Human
	Gene symbol	KPNB1
	Gene ID	3837
	Gene name	karyopherin subunit beta 1
	Gene Alias	IMB1
	Cytomap	17q21.32
	Gene Type	protein-coding
	GO ID	GO:0000070
	UniProtAcc	B7Z752

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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
3837	KPNB1	HTA11_1938_2000001011	Human	Colorectum	AD	6.13e-08	6.69e-01	-0.0811
3837	KPNB1	HTA11_347_2000001011	Human	Colorectum	AD	2.11e-10	5.77e-01	-0.1954
3837	KPNB1	HTA11_1391_2000001011	Human	Colorectum	AD	5.65e-06	7.39e-01	-0.059
3837	KPNB1	HTA11_546_2000001011	Human	Colorectum	AD	2.53e-02	4.31e-01	-0.0842
3837	KPNB1	HTA11_7696_3000711011	Human	Colorectum	AD	1.87e-02	4.73e-01	0.0674
3837	KPNB1	HTA11_7469_2000001011	Human	Colorectum	AD	1.65e-04	8.61e-01	-0.0124
3837	KPNB1	HTA11_99999970781_79442	Human	Colorectum	MSS	9.49e-19	9.22e-01	0.294
3837	KPNB1	HTA11_99999965062_69753	Human	Colorectum	MSI-H	2.86e-07	1.27e+00	0.3487
3837	KPNB1	HTA11_99999965104_69814	Human	Colorectum	MSS	4.08e-11	8.39e-01	0.281
3837	KPNB1	HTA11_99999971662_82457	Human	Colorectum	MSS	5.94e-12	8.48e-01	0.3859
3837	KPNB1	HTA11_99999974143_84620	Human	Colorectum	MSS	6.12e-03	4.56e-01	0.3005
3837	KPNB1	A015-C-203	Human	Colorectum	FAP	9.94e-23	-4.10e-01	-0.1294
3837	KPNB1	A015-C-204	Human	Colorectum	FAP	1.71e-07	-3.40e-01	-0.0228
3837	KPNB1	A014-C-040	Human	Colorectum	FAP	1.52e-02	-3.37e-01	-0.1184
3837	KPNB1	A002-C-201	Human	Colorectum	FAP	3.29e-10	-1.82e-01	0.0324
3837	KPNB1	A002-C-203	Human	Colorectum	FAP	1.00e-03	-1.46e-01	0.2786
3837	KPNB1	A001-C-119	Human	Colorectum	FAP	9.58e-06	-3.64e-01	-0.1557
3837	KPNB1	A001-C-108	Human	Colorectum	FAP	2.46e-13	-1.95e-01	-0.0272
3837	KPNB1	A002-C-205	Human	Colorectum	FAP	1.70e-15	-2.94e-01	-0.1236
3837	KPNB1	A001-C-104	Human	Colorectum	FAP	2.30e-07	-2.41e-01	0.0184

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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
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:0072594	Colorectum	AD	establishment of protein localization to organelle	148/3918	422/18723	7.95e-12	1.04e-09	148
GO:0051656	Colorectum	AD	establishment of organelle localization	131/3918	390/18723	3.00e-09	2.06e-07	131
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:0034504	Colorectum	AD	protein localization to nucleus	94/3918	290/18723	2.83e-06	8.09e-05	94
GO:0007265	Colorectum	AD	Ras protein signal transduction	104/3918	337/18723	1.01e-05	2.35e-04	104
GO:0017038	Colorectum	AD	protein import	67/3918	206/18723	6.34e-05	1.05e-03	67
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:0007051	Colorectum	AD	spindle organization	58/3918	184/18723	4.71e-04	5.20e-03	58
GO:1902850	Colorectum	AD	microtubule cytoskeleton organization involved in mitosis	48/3918	147/18723	5.87e-04	6.21e-03	48
GO:0090307	Colorectum	AD	mitotic spindle assembly	25/3918	65/18723	9.12e-04	8.71e-03	25
GO:0007052	Colorectum	AD	mitotic spindle organization	40/3918	120/18723	1.03e-03	9.61e-03	40
GO:0051225	Colorectum	AD	spindle assembly	37/3918	117/18723	4.32e-03	2.96e-02	37
GO:0140014	Colorectum	AD	mitotic nuclear division	78/3918	287/18723	6.48e-03	4.05e-02	78
GO:00725942	Colorectum	MSS	establishment of protein localization to organelle	139/3467	422/18723	5.75e-13	1.12e-10	139
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
GO:00516562	Colorectum	MSS	establishment of organelle localization	115/3467	390/18723	7.30e-08	3.67e-06	115

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05207	Colorectum	CRC	Chemical carcinogenesis - receptor activation	42/1091	212/8465	2.62e-03	1.75e-02	1.19e-02	42
hsa052071	Colorectum	CRC	Chemical carcinogenesis - receptor activation	42/1091	212/8465	2.62e-03	1.75e-02	1.19e-02	42
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

KPNB1

SNV

Missense_Mutation

c.1656N>T

p.Leu552Phe

p.L552F

Q14974

protein_coding

tolerated(0.08)

benign(0.28)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

KPNB1

SNV

Missense_Mutation

c.1996G>C

p.Val666Leu

p.V666L

Q14974

protein_coding

tolerated(0.16)

benign(0.324)

TCGA-BH-A0AZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

KPNB1

SNV

Missense_Mutation

c.304N>A

p.Glu102Lys

p.E102K

Q14974

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

KPNB1

SNV

Missense_Mutation

c.394N>A

p.Gln132Lys

p.Q132K

Q14974

protein_coding

tolerated(0.98)

benign(0)

TCGA-D8-A1J8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

nolvadex

KPNB1

SNV

Missense_Mutation

c.1656G>T

p.Leu552Phe

p.L552F

Q14974

protein_coding

tolerated(0.08)

benign(0.28)

TCGA-E9-A227-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

KPNB1

SNV

Missense_Mutation

c.1270N>T

p.Val424Phe

p.V424F

Q14974

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-E9-A243-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

KPNB1

insertion

Nonsense_Mutation

novel

c.442_443insGGGATGACTGGTTTTGTTTCT

p.Glu148delinsGlyAspAspTrpPheCysPheTer

p.E148delinsGDDWFCF*

Q14974

protein_coding

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

KPNB1

insertion

In_Frame_Ins

novel

c.444_445insGTTCTAGGGCAGTGT

p.Glu148_Ser149insValLeuGlyGlnCys

p.E148_S149insVLGQC

Q14974

protein_coding

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

KPNB1

insertion

Nonsense_Mutation

novel

c.1935_1936insGAATGTCAAGGTTAATTT

p.Lys645_Tyr646insGluCysGlnGlyTerPhe

p.K645_Y646insECQG*F

Q14974

protein_coding

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

KPNB1

deletion

Frame_Shift_Del

novel

c.2226delC

p.Ser743ProfsTer16

p.S743Pfs*16

Q14974

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

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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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