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: GSN

Gene summary for GSN

Gene summary.

Gene information	Species	Human
	Gene symbol	GSN
	Gene ID	2934
	Gene name	gelsolin
	Gene Alias	ADF
	Cytomap	9q33.2
	Gene Type	protein-coding
	GO ID	GO:0001766
	UniProtAcc	P06396

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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
2934	GSN	GSM4909281	Human	Breast	IDC	3.06e-14	5.01e-01	0.21
2934	GSN	GSM4909282	Human	Breast	IDC	2.18e-10	4.57e-01	-0.0288
2934	GSN	GSM4909285	Human	Breast	IDC	6.11e-17	5.13e-01	0.21
2934	GSN	GSM4909293	Human	Breast	IDC	7.65e-11	-4.54e-01	0.1581
2934	GSN	GSM4909294	Human	Breast	IDC	8.41e-09	-3.29e-01	0.2022
2934	GSN	GSM4909295	Human	Breast	IDC	2.57e-14	5.99e-01	0.0898
2934	GSN	GSM4909296	Human	Breast	IDC	4.53e-20	-4.85e-01	0.1524
2934	GSN	GSM4909297	Human	Breast	IDC	7.50e-12	-2.81e-01	0.1517
2934	GSN	GSM4909298	Human	Breast	IDC	4.79e-10	-4.03e-01	0.1551
2934	GSN	GSM4909301	Human	Breast	IDC	2.03e-25	-5.52e-01	0.1577
2934	GSN	GSM4909304	Human	Breast	IDC	4.31e-11	-3.89e-01	0.1636
2934	GSN	GSM4909306	Human	Breast	IDC	6.10e-09	-3.42e-01	0.1564
2934	GSN	GSM4909307	Human	Breast	IDC	2.52e-13	-4.44e-01	0.1569
2934	GSN	GSM4909308	Human	Breast	IDC	4.92e-15	-5.38e-01	0.158
2934	GSN	GSM4909311	Human	Breast	IDC	8.67e-33	-4.74e-01	0.1534
2934	GSN	GSM4909312	Human	Breast	IDC	2.27e-25	-5.21e-01	0.1552
2934	GSN	GSM4909313	Human	Breast	IDC	2.52e-02	8.66e-02	0.0391
2934	GSN	GSM4909319	Human	Breast	IDC	6.79e-37	-5.87e-01	0.1563
2934	GSN	GSM4909320	Human	Breast	IDC	1.44e-11	-6.14e-01	0.1575
2934	GSN	GSM4909321	Human	Breast	IDC	2.08e-24	-4.77e-01	0.1559

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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
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:00451851	Colorectum	SER	maintenance of protein location	26/2897	94/18723	1.76e-03	1.81e-02	26
GO:00467181	Colorectum	SER	viral entry into host cell	36/2897	144/18723	1.95e-03	1.96e-02	36
GO:00432801	Colorectum	SER	positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	33/2897	129/18723	1.97e-03	1.97e-02	33
GO:0043500	Colorectum	SER	muscle adaptation	31/2897	121/18723	2.58e-03	2.38e-02	31
GO:19018791	Colorectum	SER	regulation of protein depolymerization	24/2897	87/18723	2.69e-03	2.44e-02	24
GO:0031579	Colorectum	SER	membrane raft organization	10/2897	25/18723	2.70e-03	2.44e-02	10
GO:0003012	Colorectum	SER	muscle system process	92/2897	452/18723	2.98e-03	2.63e-02	92
GO:20010561	Colorectum	SER	positive regulation of cysteine-type endopeptidase activity	36/2897	148/18723	3.21e-03	2.76e-02	36
GO:0090075	Colorectum	SER	relaxation of muscle	12/2897	34/18723	3.60e-03	3.03e-02	12
GO:00444091	Colorectum	SER	entry into host	36/2897	151/18723	4.55e-03	3.61e-02	36
GO:00432441	Colorectum	SER	regulation of protein-containing complex disassembly	30/2897	121/18723	5.03e-03	3.88e-02	30
GO:0043903	Colorectum	SER	regulation of biological process involved in symbiotic interaction	20/2897	72/18723	5.36e-03	4.03e-02	20
GO:19018801	Colorectum	SER	negative regulation of protein depolymerization	20/2897	72/18723	5.36e-03	4.03e-02	20
GO:00516511	Colorectum	SER	maintenance of location in cell	47/2897	214/18723	7.20e-03	4.99e-02	47
GO:00160322	Colorectum	MSS	viral process	157/3467	415/18723	7.94e-21	6.19e-18	157
GO:00070152	Colorectum	MSS	actin filament organization	146/3467	442/18723	1.16e-13	2.67e-11	146
GO:00190582	Colorectum	MSS	viral life cycle	111/3467	317/18723	1.65e-12	2.95e-10	111
GO:00325352	Colorectum	MSS	regulation of cellular component size	127/3467	383/18723	3.44e-12	5.79e-10	127
GO:00329702	Colorectum	MSS	regulation of actin filament-based process	128/3467	397/18723	2.47e-11	3.49e-09	128
GO:00316472	Colorectum	MSS	regulation of protein stability	103/3467	298/18723	2.52e-11	3.49e-09	103

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa052036	Breast	Precancer	Viral carcinogenesis	27/684	204/8465	7.19e-03	4.06e-02	3.11e-02	27
hsa0520312	Breast	Precancer	Viral carcinogenesis	27/684	204/8465	7.19e-03	4.06e-02	3.11e-02	27
hsa0520322	Breast	IDC	Viral carcinogenesis	34/867	204/8465	2.82e-03	1.86e-02	1.39e-02	34
hsa0481014	Breast	IDC	Regulation of actin cytoskeleton	36/867	229/8465	5.79e-03	3.13e-02	2.34e-02	36
hsa0520332	Breast	IDC	Viral carcinogenesis	34/867	204/8465	2.82e-03	1.86e-02	1.39e-02	34
hsa0481015	Breast	IDC	Regulation of actin cytoskeleton	36/867	229/8465	5.79e-03	3.13e-02	2.34e-02	36
hsa0520341	Breast	DCIS	Viral carcinogenesis	34/846	204/8465	1.88e-03	1.27e-02	9.33e-03	34
hsa0481023	Breast	DCIS	Regulation of actin cytoskeleton	35/846	229/8465	6.89e-03	3.37e-02	2.48e-02	35
hsa052035	Breast	DCIS	Viral carcinogenesis	34/846	204/8465	1.88e-03	1.27e-02	9.33e-03	34
hsa0481033	Breast	DCIS	Regulation of actin cytoskeleton	35/846	229/8465	6.89e-03	3.37e-02	2.48e-02	35
hsa04666	Colorectum	AD	Fc gamma R-mediated phagocytosis	46/2092	97/8465	9.10e-07	1.22e-05	7.77e-06	46
hsa04810	Colorectum	AD	Regulation of actin cytoskeleton	75/2092	229/8465	3.36e-03	1.76e-02	1.12e-02	75
hsa046661	Colorectum	AD	Fc gamma R-mediated phagocytosis	46/2092	97/8465	9.10e-07	1.22e-05	7.77e-06	46
hsa048101	Colorectum	AD	Regulation of actin cytoskeleton	75/2092	229/8465	3.36e-03	1.76e-02	1.12e-02	75
hsa046662	Colorectum	SER	Fc gamma R-mediated phagocytosis	39/1580	97/8465	5.84e-07	9.70e-06	7.04e-06	39
hsa048102	Colorectum	SER	Regulation of actin cytoskeleton	60/1580	229/8465	2.74e-03	2.02e-02	1.47e-02	60
hsa046663	Colorectum	SER	Fc gamma R-mediated phagocytosis	39/1580	97/8465	5.84e-07	9.70e-06	7.04e-06	39
hsa048103	Colorectum	SER	Regulation of actin cytoskeleton	60/1580	229/8465	2.74e-03	2.02e-02	1.47e-02	60
hsa046664	Colorectum	MSS	Fc gamma R-mediated phagocytosis	45/1875	97/8465	9.30e-08	1.56e-06	9.55e-07	45
hsa048104	Colorectum	MSS	Regulation of actin cytoskeleton	68/1875	229/8465	4.27e-03	1.86e-02	1.14e-02	68

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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

GSN

insertion

Nonsense_Mutation

novel

c.276_277insATCCTCTTCTCCTCTTCCAAGAAATGAAATTTG

p.Gly92_Asp93insIleLeuPheSerSerSerLysLysTerAsnLeu

p.G92_D93insILFSSSKK*NL

P06396

protein_coding

TCGA-A8-A08T-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

GSN

deletion

Frame_Shift_Del

novel

c.493delC

p.Leu165Ter

p.L165*

P06396

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

GSN

deletion

Frame_Shift_Del

novel

c.2094delC

p.Met699CysfsTer26

p.M699Cfs*26

P06396

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

GSN

SNV

Missense_Mutation

novel

c.1504G>C

p.Glu502Gln

p.E502Q

P06396

protein_coding

deleterious(0)

probably_damaging(0.924)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

GSN

SNV

Missense_Mutation

c.65C>T

p.Ser22Leu

p.S22L

P06396

protein_coding

tolerated_low_confidence(0.17)

benign(0.012)

TCGA-Q1-A73P-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

GSN

SNV

Missense_Mutation

novel

c.2002N>T

p.Arg668Cys

p.R668C

P06396

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-VS-A8EC-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

carboplatin

GSN

SNV

Missense_Mutation

c.437A>G

p.His146Arg

p.H146R

P06396

protein_coding

deleterious(0.02)

probably_damaging(0.985)

TCGA-A6-2686-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

GSN

SNV

Missense_Mutation

c.2320N>T

p.Asp774Tyr

p.D774Y

P06396

protein_coding

deleterious(0)

benign(0.159)

TCGA-A6-6782-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

GSN

SNV

Missense_Mutation

novel

c.611N>A

p.Pro204His

p.P204H

P06396

protein_coding

deleterious(0.03)

probably_damaging(0.925)

TCGA-AA-3949-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

GSN

SNV

Missense_Mutation

c.1616N>C

p.Phe539Ser

p.F539S

P06396

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-CA-6718-01

Colorectum

colon adenocarcinoma

Male

<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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