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:0048193	Colorectum	AD	Golgi vesicle transport	109/3918	296/18723	1.80e-10	1.68e-08	109
GO:0051656	Colorectum	AD	establishment of organelle localization	131/3918	390/18723	3.00e-09	2.06e-07	131
GO:0006900	Colorectum	AD	vesicle budding from membrane	32/3918	61/18723	5.38e-08	2.81e-06	32
GO:0016050	Colorectum	AD	vesicle organization	101/3918	300/18723	1.65e-07	7.17e-06	101
GO:0051650	Colorectum	AD	establishment of vesicle localization	57/3918	161/18723	1.47e-05	3.15e-04	57
GO:0051648	Colorectum	AD	vesicle localization	59/3918	177/18723	7.83e-05	1.25e-03	59
GO:0009306	Colorectum	AD	protein secretion	105/3918	359/18723	1.05e-04	1.57e-03	105
GO:0035592	Colorectum	AD	establishment of protein localization to extracellular region	105/3918	360/18723	1.18e-04	1.73e-03	105
GO:0071692	Colorectum	AD	protein localization to extracellular region	106/3918	368/18723	1.86e-04	2.49e-03	106
GO:0006903	Colorectum	AD	vesicle targeting	19/3918	45/18723	9.94e-04	9.28e-03	19
GO:0048194	Colorectum	AD	Golgi vesicle budding	7/3918	10/18723	1.15e-03	1.04e-02	7
GO:0006901	Colorectum	AD	vesicle coating	9/3918	17/18723	3.57e-03	2.57e-02	9
GO:00516561	Colorectum	SER	establishment of organelle localization	100/2897	390/18723	1.11e-07	6.79e-06	100
GO:00481931	Colorectum	SER	Golgi vesicle transport	79/2897	296/18723	4.20e-07	2.15e-05	79
GO:00069001	Colorectum	SER	vesicle budding from membrane	23/2897	61/18723	1.95e-05	5.66e-04	23
GO:00516501	Colorectum	SER	establishment of vesicle localization	42/2897	161/18723	3.38e-04	5.35e-03	42
GO:00160501	Colorectum	SER	vesicle organization	69/2897	300/18723	3.59e-04	5.61e-03	69
GO:00093061	Colorectum	SER	protein secretion	79/2897	359/18723	5.99e-04	8.19e-03	79
GO:00355921	Colorectum	SER	establishment of protein localization to extracellular region	79/2897	360/18723	6.54e-04	8.77e-03	79
GO:00716921	Colorectum	SER	protein localization to extracellular region	80/2897	368/18723	8.13e-04	1.01e-02	80

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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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