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: KPNA6

Gene summary for KPNA6

Gene summary.

Gene information	Species	Human
	Gene symbol	KPNA6
	Gene ID	23633
	Gene name	karyopherin subunit alpha 6
	Gene Alias	IPOA7
	Cytomap	1p35.2
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	O60684

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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
23633	KPNA6	HTA11_3410_2000001011	Human	Colorectum	AD	3.92e-04	1.33e-01	0.0155
23633	KPNA6	HTA11_1938_2000001011	Human	Colorectum	AD	8.72e-04	4.98e-01	-0.0811
23633	KPNA6	HTA11_78_2000001011	Human	Colorectum	AD	2.92e-03	3.98e-01	-0.1088
23633	KPNA6	HTA11_347_2000001011	Human	Colorectum	AD	5.76e-14	5.12e-01	-0.1954
23633	KPNA6	HTA11_2112_2000001011	Human	Colorectum	SER	2.34e-04	7.04e-01	-0.2196
23633	KPNA6	HTA11_1391_2000001011	Human	Colorectum	AD	2.71e-12	6.73e-01	-0.059
23633	KPNA6	HTA11_546_2000001011	Human	Colorectum	AD	1.15e-03	4.86e-01	-0.0842
23633	KPNA6	HTA11_866_3004761011	Human	Colorectum	AD	4.21e-03	2.57e-01	0.096
23633	KPNA6	HTA11_4255_2000001011	Human	Colorectum	SER	3.13e-03	4.89e-01	0.0446
23633	KPNA6	HTA11_6818_2000001021	Human	Colorectum	AD	2.16e-04	3.67e-01	0.0588
23633	KPNA6	HTA11_99999965104_69814	Human	Colorectum	MSS	6.54e-08	5.33e-01	0.281
23633	KPNA6	HTA11_99999971662_82457	Human	Colorectum	MSS	1.04e-08	6.84e-01	0.3859
23633	KPNA6	A002-C-010	Human	Colorectum	FAP	1.72e-02	-1.04e-01	0.242
23633	KPNA6	A015-C-203	Human	Colorectum	FAP	6.62e-13	-2.43e-01	-0.1294
23633	KPNA6	A002-C-201	Human	Colorectum	FAP	1.51e-06	-2.75e-01	0.0324
23633	KPNA6	A001-C-108	Human	Colorectum	FAP	6.25e-07	-1.15e-01	-0.0272
23633	KPNA6	A002-C-205	Human	Colorectum	FAP	7.30e-07	-1.69e-01	-0.1236
23633	KPNA6	A015-C-006	Human	Colorectum	FAP	4.21e-05	-1.42e-01	-0.0994
23633	KPNA6	A015-C-106	Human	Colorectum	FAP	1.55e-08	-2.35e-01	-0.0511
23633	KPNA6	A002-C-114	Human	Colorectum	FAP	4.86e-05	-1.98e-01	-0.1561

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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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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
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:000181910	Oral cavity	OSCC	positive regulation of cytokine production	213/7305	467/18723	1.93e-03	8.96e-03	213
GO:00447067	Oral cavity	OSCC	multi-multicellular organism process	105/7305	220/18723	5.05e-03	1.97e-02	105
GO:00447664	Oral cavity	OSCC	multi-organism transport	14/7305	21/18723	9.54e-03	3.39e-02	14
GO:19025794	Oral cavity	OSCC	multi-organism localization	14/7305	21/18723	9.54e-03	3.39e-02	14
GO:0016032110	Oral cavity	LP	viral process	211/4623	415/18723	4.06e-31	3.18e-28	211
GO:007259419	Oral cavity	LP	establishment of protein localization to organelle	205/4623	422/18723	6.76e-27	3.85e-24	205
GO:0019058110	Oral cavity	LP	viral life cycle	161/4623	317/18723	5.99e-24	2.21e-21	161
GO:003450416	Oral cavity	LP	protein localization to nucleus	133/4623	290/18723	2.41e-15	3.35e-13	133
GO:0019079110	Oral cavity	LP	viral genome replication	73/4623	131/18723	2.78e-14	3.11e-12	73
GO:0050792110	Oral cavity	LP	regulation of viral process	83/4623	164/18723	6.50e-13	5.74e-11	83
GO:000691318	Oral cavity	LP	nucleocytoplasmic transport	130/4623	301/18723	1.19e-12	9.77e-11	130
GO:005116918	Oral cavity	LP	nuclear transport	130/4623	301/18723	1.19e-12	9.77e-11	130
GO:001703816	Oral cavity	LP	protein import	95/4623	206/18723	1.55e-11	1.13e-09	95
GO:1903900110	Oral cavity	LP	regulation of viral life cycle	72/4623	148/18723	2.23e-10	1.19e-08	72
GO:004852418	Oral cavity	LP	positive regulation of viral process	40/4623	65/18723	3.14e-10	1.64e-08	40
GO:190390216	Oral cavity	LP	positive regulation of viral life cycle	19/4623	29/18723	3.94e-06	8.19e-05	19
GO:005117013	Oral cavity	LP	import into nucleus	65/4623	159/18723	4.78e-06	9.69e-05	65
GO:000660612	Oral cavity	LP	protein import into nucleus	62/4623	155/18723	1.76e-05	3.04e-04	62
GO:006013515	Oral cavity	LP	maternal process involved in female pregnancy	25/4623	62/18723	4.74e-03	3.00e-02	25
GO:000756515	Oral cavity	LP	female pregnancy	63/4623	193/18723	7.56e-03	4.17e-02	63

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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
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
hsa0516410	Liver	Cirrhotic	Influenza A	66/2530	171/8465	8.56e-03	2.91e-02	1.79e-02	66
hsa0516411	Liver	Cirrhotic	Influenza A	66/2530	171/8465	8.56e-03	2.91e-02	1.79e-02	66
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
hsa0516412	Lung	IAC	Influenza A	35/1053	171/8465	1.82e-03	1.00e-02	6.66e-03	35
hsa0516413	Lung	IAC	Influenza A	35/1053	171/8465	1.82e-03	1.00e-02	6.66e-03	35
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
hsa0516424	Oral cavity	LP	Influenza A	80/2418	171/8465	2.56e-07	3.41e-06	2.20e-06	80
hsa030132	Oral cavity	LP	Nucleocytoplasmic transport	53/2418	108/8465	4.68e-06	4.10e-05	2.64e-05	53

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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

KPNA6

SNV

Missense_Mutation

c.1168N>A

p.Ala390Thr

p.A390T

O60684

protein_coding

deleterious(0.01)

possibly_damaging(0.481)

TCGA-A2-A0CT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

KPNA6

SNV

Missense_Mutation

c.128G>A

p.Arg43Gln

p.R43Q

O60684

protein_coding

deleterious(0)

probably_damaging(0.941)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

KPNA6

SNV

Missense_Mutation

novel

c.1153G>A

p.Glu385Lys

p.E385K

O60684

protein_coding

tolerated(0.31)

benign(0.033)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

KPNA6

SNV

Missense_Mutation

novel

c.981N>G

p.Ile327Met

p.I327M

O60684

protein_coding

tolerated(0.38)

benign(0.01)

TCGA-S3-A6ZF-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

KPNA6

insertion

Frame_Shift_Ins

novel

c.849_850insTGGAGAT

p.Asn284TrpfsTer3

p.N284Wfs*3

O60684

protein_coding

TCGA-BH-A0HY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

taxotere

KPNA6

insertion

In_Frame_Ins

novel

c.851_852insAGATACAACTTCCATTTCTCCCAT

p.Asn284delinsLysAspThrThrSerIleSerProIle

p.N284delinsKDTTSISPI

O60684

protein_coding

TCGA-BH-A0HY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

taxotere

KPNA6

deletion

Frame_Shift_Del

novel

c.1480delG

p.Ala494ProfsTer11

p.A494Pfs*11

O60684

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

KPNA6

deletion

Frame_Shift_Del

novel

c.1436delN

p.Ile479MetfsTer26

p.I479Mfs*26

O60684

protein_coding

TCGA-S3-AA17-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

anastrozole

KPNA6

SNV

Missense_Mutation

c.86N>A

p.Arg29Gln

p.R29Q

O60684

protein_coding

deleterious(0)

probably_damaging(0.921)

TCGA-A6-3810-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

KPNA6

SNV

Missense_Mutation

rs201663407

c.1519G>A

p.Asp507Asn

p.D507N

O60684

protein_coding

deleterious(0.02)

benign(0.009)

TCGA-A6-5661-01

Colorectum

colon adenocarcinoma

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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