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: SRPK2

Gene summary for SRPK2

Gene summary.

Gene information	Species	Human
	Gene symbol	SRPK2
	Gene ID	6733
	Gene name	SRSF protein kinase 2
	Gene Alias	SFRSK2
	Cytomap	7q22.3
	Gene Type	protein-coding
	GO ID	GO:0000245
	UniProtAcc	A0A024R704

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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
6733	SRPK2	CA_HPV_1	Human	Cervix	CC	1.32e-02	-1.40e-01	0.0264
6733	SRPK2	CCI_1	Human	Cervix	CC	6.86e-21	1.69e+00	0.528
6733	SRPK2	CCI_2	Human	Cervix	CC	3.73e-08	1.34e+00	0.5249
6733	SRPK2	CCI_3	Human	Cervix	CC	2.46e-22	1.39e+00	0.516
6733	SRPK2	HTA11_3410_2000001011	Human	Colorectum	AD	2.41e-05	-2.80e-01	0.0155
6733	SRPK2	A001-C-207	Human	Colorectum	FAP	7.81e-04	-2.37e-01	0.1278
6733	SRPK2	A015-C-203	Human	Colorectum	FAP	1.45e-33	-5.26e-01	-0.1294
6733	SRPK2	A015-C-204	Human	Colorectum	FAP	5.80e-09	-4.68e-01	-0.0228
6733	SRPK2	A014-C-040	Human	Colorectum	FAP	3.90e-04	-3.30e-01	-0.1184
6733	SRPK2	A002-C-201	Human	Colorectum	FAP	7.17e-13	-2.58e-01	0.0324
6733	SRPK2	A001-C-119	Human	Colorectum	FAP	3.90e-05	-2.63e-01	-0.1557
6733	SRPK2	A001-C-108	Human	Colorectum	FAP	6.11e-16	-3.63e-01	-0.0272
6733	SRPK2	A002-C-205	Human	Colorectum	FAP	3.38e-25	-3.80e-01	-0.1236
6733	SRPK2	A001-C-104	Human	Colorectum	FAP	6.07e-03	-3.21e-01	0.0184
6733	SRPK2	A015-C-005	Human	Colorectum	FAP	9.12e-05	-2.46e-01	-0.0336
6733	SRPK2	A015-C-006	Human	Colorectum	FAP	7.24e-18	-4.82e-01	-0.0994
6733	SRPK2	A015-C-106	Human	Colorectum	FAP	4.79e-11	-3.02e-01	-0.0511
6733	SRPK2	A002-C-114	Human	Colorectum	FAP	3.78e-21	-4.28e-01	-0.1561
6733	SRPK2	A015-C-104	Human	Colorectum	FAP	9.85e-32	-4.82e-01	-0.1899
6733	SRPK2	A001-C-014	Human	Colorectum	FAP	1.94e-11	-3.35e-01	0.0135

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
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
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:1901216111	Esophagus	ESCC	positive regulation of neuron death	65/8552	97/18723	1.76e-05	1.56e-04	65
GO:004507015	Esophagus	ESCC	positive regulation of viral genome replication	24/8552	30/18723	1.27e-04	8.67e-04	24
GO:0043525110	Esophagus	ESCC	positive regulation of neuron apoptotic process	40/8552	58/18723	2.83e-04	1.71e-03	40
GO:004352317	Esophagus	ESCC	regulation of neuron apoptotic process	122/8552	212/18723	3.21e-04	1.90e-03	122
GO:000024514	Esophagus	ESCC	spliceosomal complex assembly	48/8552	79/18723	4.93e-03	1.89e-02	48
GO:19033116	Liver	NAFLD	regulation of mRNA metabolic process	66/1882	288/18723	1.06e-10	2.96e-08	66
GO:00160327	Liver	NAFLD	viral process	80/1882	415/18723	7.71e-09	1.07e-06	80
GO:00181055	Liver	NAFLD	peptidyl-serine phosphorylation	63/1882	315/18723	7.45e-08	6.60e-06	63
GO:00182094	Liver	NAFLD	peptidyl-serine modification	64/1882	338/18723	4.65e-07	2.89e-05	64
GO:00434847	Liver	NAFLD	regulation of RNA splicing	35/1882	148/18723	1.14e-06	5.55e-05	35
GO:00506846	Liver	NAFLD	regulation of mRNA processing	33/1882	137/18723	1.47e-06	6.73e-05	33
GO:00480247	Liver	NAFLD	regulation of mRNA splicing, via spliceosome	26/1882	101/18723	5.10e-06	1.89e-04	26
GO:00190587	Liver	NAFLD	viral life cycle	57/1882	317/18723	1.00e-05	3.18e-04	57
GO:00226137	Liver	NAFLD	ribonucleoprotein complex biogenesis	76/1882	463/18723	1.19e-05	3.67e-04	76
GO:00226187	Liver	NAFLD	ribonucleoprotein complex assembly	42/1882	220/18723	3.40e-05	8.80e-04	42
GO:00083807	Liver	NAFLD	RNA splicing	70/1882	434/18723	4.62e-05	1.10e-03	70
GO:00718267	Liver	NAFLD	ribonucleoprotein complex subunit organization	42/1882	227/18723	7.21e-05	1.51e-03	42
GO:00450705	Liver	NAFLD	positive regulation of viral genome replication	10/1882	30/18723	4.67e-04	6.74e-03	10
GO:00190797	Liver	NAFLD	viral genome replication	26/1882	131/18723	5.40e-04	7.38e-03	26
GO:00003777	Liver	NAFLD	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	51/1882	320/18723	6.21e-04	8.18e-03	51

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

SRPK2

SNV

Missense_Mutation

novel

c.736N>A

p.Glu246Lys

p.E246K

P78362

protein_coding

deleterious(0.02)

probably_damaging(0.986)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

SRPK2

SNV

Missense_Mutation

c.536N>C

p.Val179Ala

p.V179A

P78362

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SRPK2

SNV

Missense_Mutation

c.406N>A

p.Glu136Lys

p.E136K

P78362

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-GM-A2DH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

SRPK2

insertion

Frame_Shift_Ins

novel

c.1735_1736insTAGAGAGTGCTGTGTGGAGA

p.Trp579LeufsTer39

p.W579Lfs*39

P78362

protein_coding

TCGA-AN-A0FX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SRPK2

insertion

Nonsense_Mutation

novel

c.964_965insATTGAATGTAAGTTGCCTTGGTCATCACAATCCATGTAAAGGAG

p.Pro322HisfsTer2

p.P322Hfs*2

P78362

protein_coding

TCGA-BH-A0HK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

SRPK2

SNV

Missense_Mutation

c.169N>C

p.Glu57Gln

p.E57Q

P78362

protein_coding

deleterious(0.04)

probably_damaging(0.994)

TCGA-EK-A2H0-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SRPK2

SNV

Missense_Mutation

c.57G>T

p.Glu19Asp

p.E19D

P78362

protein_coding

tolerated(0.33)

benign(0.388)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SRPK2

SNV

Missense_Mutation

c.277N>T

p.His93Tyr

p.H93Y

P78362

protein_coding

deleterious(0)

probably_damaging(0.977)

TCGA-IR-A3LI-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SRPK2

SNV

Missense_Mutation

novel

c.766N>T

p.Pro256Ser

p.P256S

P78362

protein_coding

deleterious(0.01)

probably_damaging(0.998)

TCGA-VS-A958-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SRPK2

SNV

Missense_Mutation

c.169N>C

p.Glu57Gln

p.E57Q

P78362

protein_coding

deleterious(0.04)

probably_damaging(0.994)

TCGA-ZJ-A8QQ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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
6733	SRPK2	SERINE THREONINE KINASE, KINASE, ENZYME, DRUGGABLE GENOME	inhibitor	249565786

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