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: TNPO3

Gene summary for TNPO3

Gene summary.

Gene information	Species	Human
	Gene symbol	TNPO3
	Gene ID	23534
	Gene name	transportin 3
	Gene Alias	IPO12
	Cytomap	7q32.1
	Gene Type	protein-coding
	GO ID	GO:0006606
	UniProtAcc	B3KMX1

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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
23534	TNPO3	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	9.15e-10	2.02e-01	-0.1869
23534	TNPO3	GSM6177620_NYU_UCEC1_lib2_lib2	Human	Endometrium	EEC	6.68e-08	1.80e-01	-0.1875
23534	TNPO3	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	1.91e-12	9.90e-02	-0.1883
23534	TNPO3	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	1.02e-07	2.14e-01	-0.1934
23534	TNPO3	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	6.87e-11	1.87e-01	-0.1917
23534	TNPO3	GSM6177622_NYU_UCEC3_lib2_lib2	Human	Endometrium	EEC	2.20e-12	5.90e-02	-0.1916
23534	TNPO3	LZE2T	Human	Esophagus	ESCC	9.89e-04	2.85e-01	0.082
23534	TNPO3	LZE4T	Human	Esophagus	ESCC	5.88e-11	3.44e-01	0.0811
23534	TNPO3	LZE7T	Human	Esophagus	ESCC	3.78e-08	4.76e-01	0.0667
23534	TNPO3	LZE20T	Human	Esophagus	ESCC	4.51e-11	2.41e-01	0.0662
23534	TNPO3	LZE22T	Human	Esophagus	ESCC	5.21e-03	1.78e-01	0.068
23534	TNPO3	LZE24T	Human	Esophagus	ESCC	1.88e-11	3.03e-01	0.0596
23534	TNPO3	LZE21T	Human	Esophagus	ESCC	2.44e-07	1.92e-01	0.0655
23534	TNPO3	P1T-E	Human	Esophagus	ESCC	4.05e-09	2.85e-01	0.0875
23534	TNPO3	P2T-E	Human	Esophagus	ESCC	6.89e-12	1.56e-01	0.1177
23534	TNPO3	P4T-E	Human	Esophagus	ESCC	1.26e-21	3.51e-01	0.1323
23534	TNPO3	P5T-E	Human	Esophagus	ESCC	1.24e-11	2.18e-01	0.1327
23534	TNPO3	P8T-E	Human	Esophagus	ESCC	4.25e-17	2.28e-01	0.0889
23534	TNPO3	P9T-E	Human	Esophagus	ESCC	9.01e-14	2.26e-01	0.1131
23534	TNPO3	P10T-E	Human	Esophagus	ESCC	1.23e-21	4.37e-01	0.116

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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
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:007259415	Endometrium	EEC	establishment of protein localization to organelle	94/2168	422/18723	2.22e-10	2.51e-08	94
GO:003450413	Endometrium	EEC	protein localization to nucleus	60/2168	290/18723	5.09e-06	1.26e-04	60
GO:000691314	Endometrium	EEC	nucleocytoplasmic transport	59/2168	301/18723	3.31e-05	5.65e-04	59
GO:005116914	Endometrium	EEC	nuclear transport	59/2168	301/18723	3.31e-05	5.65e-04	59
GO:001703813	Endometrium	EEC	protein import	40/2168	206/18723	6.94e-04	6.66e-03	40
GO:0072594110	Esophagus	ESCC	establishment of protein localization to organelle	311/8552	422/18723	3.02e-32	2.13e-29	311
GO:0006913110	Esophagus	ESCC	nucleocytoplasmic transport	230/8552	301/18723	6.04e-28	2.02e-25	230
GO:0051169110	Esophagus	ESCC	nuclear transport	230/8552	301/18723	6.04e-28	2.02e-25	230
GO:003450418	Esophagus	ESCC	protein localization to nucleus	211/8552	290/18723	4.06e-21	6.60e-19	211
GO:001703818	Esophagus	ESCC	protein import	149/8552	206/18723	5.90e-15	3.31e-13	149
GO:005117014	Esophagus	ESCC	import into nucleus	111/8552	159/18723	5.69e-10	1.44e-08	111
GO:000660613	Esophagus	ESCC	protein import into nucleus	108/8552	155/18723	1.16e-09	2.77e-08	108
GO:00069137	Liver	NAFLD	nucleocytoplasmic transport	51/1882	301/18723	1.39e-04	2.62e-03	51
GO:00511697	Liver	NAFLD	nuclear transport	51/1882	301/18723	1.39e-04	2.62e-03	51
GO:00725947	Liver	NAFLD	establishment of protein localization to organelle	62/1882	422/18723	1.48e-03	1.64e-02	62
GO:00345046	Liver	NAFLD	protein localization to nucleus	45/1882	290/18723	2.16e-03	2.10e-02	45
GO:007259422	Liver	HCC	establishment of protein localization to organelle	299/7958	422/18723	1.06e-32	6.10e-30	299
GO:000691322	Liver	HCC	nucleocytoplasmic transport	208/7958	301/18723	5.51e-21	8.12e-19	208
GO:005116922	Liver	HCC	nuclear transport	208/7958	301/18723	5.51e-21	8.12e-19	208
GO:003450421	Liver	HCC	protein localization to nucleus	194/7958	290/18723	2.84e-17	2.85e-15	194

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
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
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
hsa03013	Liver	HCC	Nucleocytoplasmic transport	81/4020	108/8465	4.28e-09	6.83e-08	3.80e-08	81
hsa032502	Liver	HCC	Viral life cycle - HIV-1	46/4020	63/8465	3.25e-05	1.88e-04	1.04e-04	46
hsa030131	Liver	HCC	Nucleocytoplasmic transport	81/4020	108/8465	4.28e-09	6.83e-08	3.80e-08	81
hsa0325011	Liver	HCC	Viral life cycle - HIV-1	46/4020	63/8465	3.25e-05	1.88e-04	1.04e-04	46
hsa030136	Oral cavity	OSCC	Nucleocytoplasmic transport	82/3704	108/8465	7.93e-12	1.33e-10	6.77e-11	82
hsa032508	Oral cavity	OSCC	Viral life cycle - HIV-1	45/3704	63/8465	7.62e-06	3.59e-05	1.83e-05	45
hsa0301311	Oral cavity	OSCC	Nucleocytoplasmic transport	82/3704	108/8465	7.93e-12	1.33e-10	6.77e-11	82
hsa0325013	Oral cavity	OSCC	Viral life cycle - HIV-1	45/3704	63/8465	7.62e-06	3.59e-05	1.83e-05	45
hsa030132	Oral cavity	LP	Nucleocytoplasmic transport	53/2418	108/8465	4.68e-06	4.10e-05	2.64e-05	53
hsa0325022	Oral cavity	LP	Viral life cycle - HIV-1	32/2418	63/8465	1.55e-04	9.08e-04	5.86e-04	32
hsa030133	Oral cavity	LP	Nucleocytoplasmic transport	53/2418	108/8465	4.68e-06	4.10e-05	2.64e-05	53
hsa0325031	Oral cavity	LP	Viral life cycle - HIV-1	32/2418	63/8465	1.55e-04	9.08e-04	5.86e-04	32
hsa030134	Oral cavity	EOLP	Nucleocytoplasmic transport	34/1218	108/8465	4.24e-06	2.91e-05	1.72e-05	34
hsa0325041	Oral cavity	EOLP	Viral life cycle - HIV-1	16/1218	63/8465	1.46e-02	3.77e-02	2.22e-02	16
hsa030135	Oral cavity	EOLP	Nucleocytoplasmic transport	34/1218	108/8465	4.24e-06	2.91e-05	1.72e-05	34
hsa032505	Oral cavity	EOLP	Viral life cycle - HIV-1	16/1218	63/8465	1.46e-02	3.77e-02	2.22e-02	16

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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

TNPO3

SNV

Missense_Mutation

c.839N>G

p.Tyr280Cys

p.Y280C

Q9Y5L0

protein_coding

deleterious(0)

probably_damaging(0.962)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TNPO3

SNV

Missense_Mutation

c.254C>G

p.Ser85Cys

p.S85C

Q9Y5L0

protein_coding

deleterious(0)

possibly_damaging(0.779)

TCGA-AR-A24U-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

TNPO3

SNV

Missense_Mutation

rs370293580

c.1616N>G

p.Asn539Ser

p.N539S

Q9Y5L0

protein_coding

tolerated(1)

benign(0.005)

TCGA-B6-A0I1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TNPO3

SNV

Missense_Mutation

c.266N>T

p.Ser89Leu

p.S89L

Q9Y5L0

protein_coding

deleterious(0)

probably_damaging(0.988)

TCGA-BH-A0AW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

TNPO3

SNV

Missense_Mutation

c.647N>A

p.Ser216Asn

p.S216N

Q9Y5L0

protein_coding

tolerated(0.52)

benign(0.021)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TNPO3

SNV

Missense_Mutation

novel

c.769N>C

p.Glu257Gln

p.E257Q

Q9Y5L0

protein_coding

tolerated(0.07)

probably_damaging(0.959)

TCGA-XX-A89A-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TNPO3

insertion

Frame_Shift_Ins

novel

c.481_482insGT

p.Ile161SerfsTer11

p.I161Sfs*11

Q9Y5L0

protein_coding

TCGA-AR-A0U2-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

tamoxiphen

TNPO3

insertion

Frame_Shift_Ins

rs761308428

c.2541_2542insC

p.Tyr848LeufsTer8

p.Y848Lfs*8

Q9Y5L0

protein_coding

TCGA-E9-A1NI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

TNPO3

SNV

Missense_Mutation

c.2323C>A

p.Pro775Thr

p.P775T

Q9Y5L0

protein_coding

tolerated(0.12)

benign(0.005)

TCGA-FU-A3EO-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TNPO3

SNV

Missense_Mutation

c.859N>A

p.Glu287Lys

p.E287K

Q9Y5L0

protein_coding

deleterious(0)

possibly_damaging(0.863)

TCGA-JW-A5VL-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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