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: FGA

Gene summary for FGA

Gene summary.

Gene information	Species	Human
	Gene symbol	FGA
	Gene ID	2243
	Gene name	fibrinogen alpha chain
	Gene Alias	Fib2
	Cytomap	4q31.3
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	P02671

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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
2243	FGA	NAFLD1	Human	Liver	NAFLD	1.94e-07	8.24e-01	-0.04
2243	FGA	S41	Human	Liver	Cirrhotic	1.88e-06	7.12e-01	-0.0343
2243	FGA	S43	Human	Liver	Cirrhotic	6.34e-40	1.12e+00	-0.0187
2243	FGA	S44	Human	Liver	HCC	3.17e-08	1.14e+00	-0.0083
2243	FGA	HCC1_Meng	Human	Liver	HCC	1.24e-62	1.94e-01	0.0246
2243	FGA	HCC2_Meng	Human	Liver	HCC	2.02e-25	-8.38e-01	0.0107
2243	FGA	cirrhotic1	Human	Liver	Cirrhotic	4.26e-22	2.99e-02	0.0202
2243	FGA	cirrhotic2	Human	Liver	Cirrhotic	2.01e-22	2.88e-01	0.0201
2243	FGA	cirrhotic3	Human	Liver	Cirrhotic	5.14e-06	-2.85e-01	0.0215
2243	FGA	p6	Human	Liver	Cyst	2.30e-02	-8.55e-01	-0.0218
2243	FGA	HCC1	Human	Liver	HCC	4.79e-34	6.99e+00	0.5336
2243	FGA	HCC2	Human	Liver	HCC	2.26e-37	8.23e+00	0.5341
2243	FGA	Pt13.a	Human	Liver	HCC	3.56e-41	6.22e-01	0.021
2243	FGA	Pt13.b	Human	Liver	HCC	1.35e-85	5.86e-01	0.0251
2243	FGA	Pt13.c	Human	Liver	HCC	2.13e-46	1.06e+00	0.0076
2243	FGA	Pt14.a	Human	Liver	HCC	2.68e-11	6.82e-01	0.0169
2243	FGA	Pt14.b	Human	Liver	HCC	4.09e-19	5.67e-01	0.018
2243	FGA	Pt14.c	Human	Liver	HCC	3.89e-02	4.04e-01	0.0054
2243	FGA	Pt14.d	Human	Liver	HCC	1.11e-21	6.00e-01	0.0143
2243	FGA	S027	Human	Liver	HCC	7.69e-20	4.19e+00	0.2446

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
Liver		NAFLD: Non-alcoholic fatty liver disease

∗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:001003812	Liver	Cirrhotic	response to metal ion	150/4634	373/18723	2.27e-11	1.37e-09	150
GO:005122212	Liver	Cirrhotic	positive regulation of protein transport	126/4634	303/18723	6.85e-11	3.77e-09	126
GO:002260412	Liver	Cirrhotic	regulation of cell morphogenesis	127/4634	309/18723	1.45e-10	7.44e-09	127
GO:009719112	Liver	Cirrhotic	extrinsic apoptotic signaling pathway	97/4634	219/18723	1.82e-10	9.11e-09	97
GO:00516046	Liver	Cirrhotic	protein maturation	121/4634	294/18723	3.54e-10	1.68e-08	121
GO:200123612	Liver	Cirrhotic	regulation of extrinsic apoptotic signaling pathway	72/4634	151/18723	7.80e-10	3.62e-08	72
GO:004206012	Liver	Cirrhotic	wound healing	155/4634	422/18723	2.12e-08	7.56e-07	155
GO:005125812	Liver	Cirrhotic	protein polymerization	116/4634	297/18723	2.87e-08	9.78e-07	116
GO:00316391	Liver	Cirrhotic	plasminogen activation	18/4634	24/18723	3.24e-07	7.75e-06	18
GO:001081012	Liver	Cirrhotic	regulation of cell-substrate adhesion	88/4634	221/18723	4.89e-07	1.10e-05	88
GO:190002412	Liver	Cirrhotic	regulation of substrate adhesion-dependent cell spreading	31/4634	57/18723	1.55e-06	3.02e-05	31
GO:006104112	Liver	Cirrhotic	regulation of wound healing	58/4634	134/18723	1.95e-06	3.65e-05	58
GO:00301931	Liver	Cirrhotic	regulation of blood coagulation	34/4634	66/18723	2.55e-06	4.63e-05	34
GO:003158912	Liver	Cirrhotic	cell-substrate adhesion	128/4634	363/18723	4.10e-06	6.90e-05	128
GO:19000461	Liver	Cirrhotic	regulation of hemostasis	34/4634	68/18723	6.04e-06	9.74e-05	34
GO:00086256	Liver	Cirrhotic	extrinsic apoptotic signaling pathway via death domain receptors	39/4634	82/18723	6.14e-06	9.82e-05	39
GO:001081112	Liver	Cirrhotic	positive regulation of cell-substrate adhesion	53/4634	123/18723	6.21e-06	9.88e-05	53
GO:00427301	Liver	Cirrhotic	fibrinolysis	17/4634	25/18723	6.26e-06	9.92e-05	17
GO:00316381	Liver	Cirrhotic	zymogen activation	31/4634	60/18723	6.48e-06	1.02e-04	31
GO:00508181	Liver	Cirrhotic	regulation of coagulation	35/4634	71/18723	6.67e-06	1.04e-04	35

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0517114	Liver	NAFLD	Coronavirus disease - COVID-19	111/1043	232/8465	1.01e-41	3.32e-39	2.67e-39	111
hsa04610	Liver	NAFLD	Complement and coagulation cascades	35/1043	86/8465	2.48e-11	2.04e-09	1.64e-09	35
hsa0517115	Liver	NAFLD	Coronavirus disease - COVID-19	111/1043	232/8465	1.01e-41	3.32e-39	2.67e-39	111
hsa046101	Liver	NAFLD	Complement and coagulation cascades	35/1043	86/8465	2.48e-11	2.04e-09	1.64e-09	35
hsa0517122	Liver	Cirrhotic	Coronavirus disease - COVID-19	136/2530	232/8465	3.28e-20	1.82e-18	1.12e-18	136
hsa046102	Liver	Cirrhotic	Complement and coagulation cascades	48/2530	86/8465	4.41e-07	5.44e-06	3.35e-06	48
hsa0517132	Liver	Cirrhotic	Coronavirus disease - COVID-19	136/2530	232/8465	3.28e-20	1.82e-18	1.12e-18	136
hsa046103	Liver	Cirrhotic	Complement and coagulation cascades	48/2530	86/8465	4.41e-07	5.44e-06	3.35e-06	48
hsa0517142	Liver	HCC	Coronavirus disease - COVID-19	167/4020	232/8465	1.50e-14	4.19e-13	2.33e-13	167
hsa046104	Liver	HCC	Complement and coagulation cascades	57/4020	86/8465	3.19e-04	1.45e-03	8.04e-04	57
hsa046112	Liver	HCC	Platelet activation	71/4020	124/8465	1.77e-02	4.15e-02	2.31e-02	71
hsa0517152	Liver	HCC	Coronavirus disease - COVID-19	167/4020	232/8465	1.50e-14	4.19e-13	2.33e-13	167
hsa046105	Liver	HCC	Complement and coagulation cascades	57/4020	86/8465	3.19e-04	1.45e-03	8.04e-04	57
hsa0461111	Liver	HCC	Platelet activation	71/4020	124/8465	1.77e-02	4.15e-02	2.31e-02	71
hsa0517162	Liver	Cyst	Coronavirus disease - COVID-19	75/339	232/8465	2.97e-49	4.27e-47	3.53e-47	75
hsa0517172	Liver	Cyst	Coronavirus disease - COVID-19	75/339	232/8465	2.97e-49	4.27e-47	3.53e-47	75

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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

FGA

SNV

Missense_Mutation

c.1663N>G

p.Thr555Ala

p.T555A

P02671

protein_coding

tolerated(0.08)

benign(0.046)

TCGA-A2-A0SW-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

arimidex

FGA

SNV

Missense_Mutation

c.1443N>C

p.Glu481Asp

p.E481D

P02671

protein_coding

deleterious(0.01)

probably_damaging(0.998)

TCGA-AR-A24L-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

FGA

SNV

Missense_Mutation

rs745321779

c.878G>T

p.Gly293Val

p.G293V

P02671

protein_coding

deleterious(0.01)

possibly_damaging(0.784)

TCGA-BH-A0DZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

FGA

SNV

Missense_Mutation

c.74N>T

p.Gly25Val

p.G25V

P02671

protein_coding

deleterious(0.02)

possibly_damaging(0.861)

TCGA-BH-A18V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

FGA

SNV

Missense_Mutation

c.633N>A

p.Asp211Glu

p.D211E

P02671

protein_coding

tolerated(0.13)

benign(0.001)

TCGA-C8-A274-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

FGA

SNV

Missense_Mutation

novel

c.2422N>G

p.Trp808Gly

p.W808G

P02671

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-E2-A1LA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

FGA

insertion

In_Frame_Ins

novel

c.1375_1376insAATTTACTAGTAGCACGAGTTACAACAGAGGAG

p.Arg459delinsGlnPheThrSerSerThrSerTyrAsnArgGlyGly

p.R459delinsQFTSSTSYNRGG

P02671

protein_coding

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

FGA

insertion

Nonsense_Mutation

novel

c.1980_1981insATCATTACATAAT

p.Val661IlefsTer4

p.V661Ifs*4

P02671

protein_coding

TCGA-A8-A08J-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

FGA

insertion

Nonsense_Mutation

novel

c.1771_1772insTTCTTTCCTAAATATAAAT

p.Arg591IlefsTer4

p.R591Ifs*4

P02671

protein_coding

TCGA-AO-A03R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

FGA

SNV

Missense_Mutation

c.2245N>A

p.Glu749Lys

p.E749K

P02671

protein_coding

deleterious(0.02)

benign(0.121)

TCGA-C5-A1BQ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

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
2243	FGA	CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME, FIBRINOGEN		RETEPLASE	RETEPLASE
2243	FGA	CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME, FIBRINOGEN		RECOMBINANT FACTOR IX FC FUSION PROTEIN
2243	FGA	CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME, FIBRINOGEN		ALFIMEPRASE	ALFIMEPRASE
2243	FGA	CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME, FIBRINOGEN		ANISTREPLASE	ANISTREPLASE
2243	FGA	CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME, FIBRINOGEN	inhibitor	CHEMBL1201505	FIBRINOLYSIN, HUMAN
2243	FGA	CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME, FIBRINOGEN		eptifibatide	EPTIFIBATIDE	20938371
2243	FGA	CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME, FIBRINOGEN		tirofiban	TIROFIBAN	20938371
2243	FGA	CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME, FIBRINOGEN		abciximab	ABCIXIMAB	20938371
2243	FGA	CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUGGABLE GENOME, FIBRINOGEN		ALTEPLASE	ALTEPLASE

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