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: SFPQ

Gene summary for SFPQ

Gene summary.

Gene information	Species	Human
	Gene symbol	SFPQ
	Gene ID	6421
	Gene name	splicing factor proline and glutamine rich
	Gene Alias	POMP100
	Cytomap	1p34.3
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	P23246

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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
6421	SFPQ	GSM4909286	Human	Breast	IDC	2.83e-06	7.76e-02	0.1081
6421	SFPQ	GSM4909293	Human	Breast	IDC	1.70e-07	2.70e-01	0.1581
6421	SFPQ	GSM4909296	Human	Breast	IDC	7.89e-10	-3.97e-01	0.1524
6421	SFPQ	GSM4909297	Human	Breast	IDC	3.95e-13	-2.04e-01	0.1517
6421	SFPQ	GSM4909298	Human	Breast	IDC	1.49e-02	1.14e-01	0.1551
6421	SFPQ	GSM4909311	Human	Breast	IDC	1.36e-29	-4.42e-01	0.1534
6421	SFPQ	GSM4909312	Human	Breast	IDC	8.72e-06	-9.09e-02	0.1552
6421	SFPQ	GSM4909313	Human	Breast	IDC	1.82e-04	-3.24e-01	0.0391
6421	SFPQ	GSM4909316	Human	Breast	IDC	1.62e-02	-3.71e-01	0.21
6421	SFPQ	GSM4909317	Human	Breast	IDC	2.42e-02	2.65e-01	0.1355
6421	SFPQ	GSM4909319	Human	Breast	IDC	1.77e-38	-5.44e-01	0.1563
6421	SFPQ	GSM4909320	Human	Breast	IDC	1.98e-06	-5.03e-01	0.1575
6421	SFPQ	GSM4909321	Human	Breast	IDC	6.70e-14	-3.72e-01	0.1559
6421	SFPQ	brca10	Human	Breast	Precancer	1.91e-10	-4.91e-01	-0.0029
6421	SFPQ	NCCBC14	Human	Breast	DCIS	4.45e-07	-2.57e-01	0.2021
6421	SFPQ	NCCBC2	Human	Breast	DCIS	3.57e-02	-6.31e-02	0.1554
6421	SFPQ	NCCBC5	Human	Breast	DCIS	1.32e-08	-1.48e-01	0.2046
6421	SFPQ	P1	Human	Breast	IDC	2.80e-16	-9.63e-02	0.1527
6421	SFPQ	DCIS2	Human	Breast	DCIS	9.40e-52	4.32e-01	0.0085
6421	SFPQ	HTA11_99999970781_79442	Human	Colorectum	MSS	1.34e-06	6.51e-01	0.294

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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:003647321	Stomach	CSG	cell death in response to oxidative stress	15/1034	95/18723	2.12e-04	4.04e-03	15
GO:190288221	Stomach	CSG	regulation of response to oxidative stress	15/1034	98/18723	3.01e-04	5.17e-03	15
GO:190217521	Stomach	CSG	regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	7/1034	29/18723	8.20e-04	1.11e-02	7
GO:000838011	Stomach	CSG	RNA splicing	40/1034	434/18723	1.07e-03	1.35e-02	40
GO:200123521	Stomach	CSG	positive regulation of apoptotic signaling pathway	16/1034	126/18723	1.56e-03	1.75e-02	16
GO:000037711	Stomach	CSG	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	31/1034	320/18723	1.74e-03	1.89e-02	31
GO:000039811	Stomach	CSG	mRNA splicing, via spliceosome	31/1034	320/18723	1.74e-03	1.89e-02	31
GO:000037511	Stomach	CSG	RNA splicing, via transesterification reactions	31/1034	324/18723	2.11e-03	2.17e-02	31
GO:000863121	Stomach	CSG	intrinsic apoptotic signaling pathway in response to oxidative stress	8/1034	45/18723	2.93e-03	2.74e-02	8
GO:00022531	Stomach	CSG	activation of immune response	33/1034	375/18723	5.70e-03	4.54e-02	33
GO:000762311	Stomach	CSG	circadian rhythm	21/1034	210/18723	6.27e-03	4.86e-02	21
GO:009719331	Stomach	CAG	intrinsic apoptotic signaling pathway	31/552	288/18723	5.37e-10	1.47e-07	31
GO:200124231	Stomach	CAG	regulation of intrinsic apoptotic signaling pathway	23/552	164/18723	5.59e-10	1.47e-07	23
GO:200123331	Stomach	CAG	regulation of apoptotic signaling pathway	34/552	356/18723	1.85e-09	3.66e-07	34
GO:000697931	Stomach	CAG	response to oxidative stress	33/552	446/18723	1.33e-06	8.49e-05	33
GO:000838021	Stomach	CAG	RNA splicing	32/552	434/18723	2.08e-06	1.16e-04	32
GO:006219731	Stomach	CAG	cellular response to chemical stress	26/552	337/18723	8.47e-06	3.67e-04	26
GO:190217531	Stomach	CAG	regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	7/552	29/18723	1.65e-05	6.26e-04	7
GO:000037721	Stomach	CAG	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	24/552	320/18723	2.97e-05	1.02e-03	24
GO:000039821	Stomach	CAG	mRNA splicing, via spliceosome	24/552	320/18723	2.97e-05	1.02e-03	24

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
SFPQ	CD8TEXP	Stomach	GC	PNRC1,GZMB,DDX3Y, etc.	1.64e-01

∗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

SFPQ

SNV

Missense_Mutation

c.1712N>A

p.Arg571Gln

p.R571Q

P23246

protein_coding

tolerated(0.07)

probably_damaging(0.978)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

SFPQ

SNV

Missense_Mutation

c.1151N>G

p.Asn384Ser

p.N384S

P23246

protein_coding

deleterious(0.02)

probably_damaging(0.992)

TCGA-BH-A0BC-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

SFPQ

SNV

Missense_Mutation

novel

c.1595N>A

p.Ala532Glu

p.A532E

P23246

protein_coding

deleterious(0.03)

benign(0.327)

TCGA-C8-A274-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

SFPQ

insertion

Nonsense_Mutation

novel

c.1028_1029insCACCCCCAGCTAATTTTTTAATTTTTTTTGTA

p.Leu344ThrfsTer4

p.L344Tfs*4

P23246

protein_coding

TCGA-A2-A04Q-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SFPQ

insertion

Frame_Shift_Ins

novel

c.1468_1469insCA

p.Tyr490SerfsTer24

p.Y490Sfs*24

P23246

protein_coding

TCGA-A2-A0ER-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

SFPQ

insertion

Nonsense_Mutation

novel

c.1467_1468insCATTTATATTCTGACATTTAGGGAAAAGATGTACTTAGTTTT

p.Glu489_Tyr490insHisLeuTyrSerAspIleTerGlyLysAspValLeuSerPhe

p.E489_Y490insHLYSDI*GKDVLSF

P23246

protein_coding

TCGA-A2-A0ER-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

SFPQ

deletion

Frame_Shift_Del

novel

c.1464delC

p.Tyr488Ter

p.Y488*

P23246

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

SFPQ

SNV

Missense_Mutation

rs751612883

c.1643G>A

p.Arg548His

p.R548H

P23246

protein_coding

deleterious(0.01)

possibly_damaging(0.869)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SFPQ

SNV

Missense_Mutation

novel

c.2089N>C

p.Glu697Gln

p.E697Q

P23246

protein_coding

deleterious(0.01)

probably_damaging(0.986)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SFPQ

SNV

Missense_Mutation

novel

c.1915N>A

p.Gly639Ser

p.G639S

P23246

protein_coding

deleterious(0.03)

probably_damaging(0.998)

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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