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: ALB

Gene summary for ALB

Gene summary.

Gene information	Species	Human
	Gene symbol	ALB
	Gene ID	213
	Gene name	albumin
	Gene Alias	FDAHT
	Cytomap	4q13.3
	Gene Type	protein-coding
	GO ID	GO:0001894
	UniProtAcc	P02768

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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
213	ALB	S43	Human	Liver	Cirrhotic	3.61e-20	3.21e-01	-0.0187
213	ALB	HCC1_Meng	Human	Liver	HCC	6.94e-16	2.83e-01	0.0246
213	ALB	HCC2_Meng	Human	Liver	HCC	8.26e-128	-2.26e+00	0.0107
213	ALB	cirrhotic1	Human	Liver	Cirrhotic	8.43e-29	-2.85e-01	0.0202
213	ALB	cirrhotic2	Human	Liver	Cirrhotic	1.59e-09	4.54e-03	0.0201
213	ALB	cirrhotic3	Human	Liver	Cirrhotic	2.33e-47	-8.64e-01	0.0215
213	ALB	p6	Human	Liver	Cyst	8.52e-36	-2.28e+00	-0.0218
213	ALB	HCC1	Human	Liver	HCC	1.70e-25	7.13e+00	0.5336
213	ALB	HCC2	Human	Liver	HCC	2.38e-28	9.69e+00	0.5341
213	ALB	HCC5	Human	Liver	HCC	2.84e-18	2.68e+00	0.4932
213	ALB	Pt13.a	Human	Liver	HCC	8.35e-08	6.50e-02	0.021
213	ALB	Pt13.b	Human	Liver	HCC	2.98e-31	-1.13e-01	0.0251
213	ALB	Pt13.c	Human	Liver	HCC	5.33e-03	8.02e-02	0.0076
213	ALB	Pt14.b	Human	Liver	HCC	8.13e-09	-1.68e-01	0.018
213	ALB	Pt14.c	Human	Liver	HCC	4.44e-08	-3.18e-01	0.0054
213	ALB	Pt14.d	Human	Liver	HCC	3.01e-23	-1.41e-01	0.0143
213	ALB	S014	Human	Liver	HCC	7.14e-33	4.12e-01	0.2254
213	ALB	S015	Human	Liver	HCC	1.09e-49	7.74e-01	0.2375
213	ALB	S016	Human	Liver	HCC	7.50e-50	-1.25e+00	0.2243
213	ALB	S027	Human	Liver	HCC	3.91e-16	4.02e+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:00602498	Cervix	CC	anatomical structure homeostasis	63/2311	314/18723	6.03e-05	8.68e-04	63
GO:00722341	Cervix	CC	metanephric nephron tubule development	7/2311	18/18723	3.99e-03	2.48e-02	7
GO:0150063	Cervix	CC	visual system development	63/2311	375/18723	6.58e-03	3.65e-02	63
GO:0001654	Cervix	CC	eye development	62/2311	371/18723	7.83e-03	4.13e-02	62
GO:0048880	Cervix	CC	sensory system development	63/2311	381/18723	9.29e-03	4.66e-02	63
GO:0072170	Cervix	CC	metanephric tubule development	7/2311	21/18723	1.04e-02	4.97e-02	7
GO:0072243	Cervix	CC	metanephric nephron epithelium development	7/2311	21/18723	1.04e-02	4.97e-02	7
GO:0010821	Colorectum	AD	regulation of mitochondrion organization	57/3918	144/18723	2.43e-07	9.92e-06	57
GO:0009636	Colorectum	AD	response to toxic substance	88/3918	262/18723	1.12e-06	3.72e-05	88
GO:0043087	Colorectum	AD	regulation of GTPase activity	110/3918	348/18723	1.64e-06	5.03e-05	110
GO:0007265	Colorectum	AD	Ras protein signal transduction	104/3918	337/18723	1.01e-05	2.35e-04	104
GO:0010822	Colorectum	AD	positive regulation of mitochondrion organization	32/3918	74/18723	1.22e-05	2.68e-04	32
GO:0051056	Colorectum	AD	regulation of small GTPase mediated signal transduction	94/3918	302/18723	1.81e-05	3.76e-04	94
GO:0098754	Colorectum	AD	detoxification	53/3918	152/18723	4.63e-05	7.98e-04	53
GO:0043547	Colorectum	AD	positive regulation of GTPase activity	75/3918	255/18723	7.95e-04	7.91e-03	75
GO:0046578	Colorectum	AD	regulation of Ras protein signal transduction	56/3918	189/18723	2.85e-03	2.14e-02	56
GO:0007266	Colorectum	AD	Rho protein signal transduction	42/3918	137/18723	4.64e-03	3.16e-02	42
GO:00510562	Colorectum	FAP	regulation of small GTPase mediated signal transduction	78/2622	302/18723	3.25e-08	2.85e-06	78
GO:00430873	Colorectum	FAP	regulation of GTPase activity	85/2622	348/18723	1.20e-07	7.68e-06	85
GO:00072652	Colorectum	FAP	Ras protein signal transduction	80/2622	337/18723	9.61e-07	4.33e-05	80

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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

ALB

SNV

Missense_Mutation

novel

c.247N>A

p.Ala83Thr

p.A83T

P02768

protein_coding

tolerated(0.06)

benign(0.068)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

ALB

SNV

Missense_Mutation

novel

c.1814N>T

p.Ala605Val

p.A605V

P02768

protein_coding

deleterious(0.02)

benign(0.041)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

ALB

SNV

Missense_Mutation

c.29N>A

p.Leu10His

p.L10H

P02768

protein_coding

deleterious(0)

possibly_damaging(0.867)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ALB

SNV

Missense_Mutation

c.1802N>T

p.Ala601Val

p.A601V

P02768

protein_coding

tolerated(0.53)

benign(0)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ALB

insertion

Nonsense_Mutation

novel

c.75_76insTCTACTTATTGAAAGAGAGAAAGGAAAAAAATATGAAACAG

p.Ala26SerfsTer4

p.A26Sfs*4

P02768

protein_coding

TCGA-A2-A0EO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

ALB

insertion

Nonsense_Mutation

novel

c.806_807insAGCATGGAGTAACTCCATAGGCCAACA

p.Cys269delinsTer

p.C269delins*

P02768

protein_coding

TCGA-BH-A0BM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

ALB

SNV

Missense_Mutation

c.1249N>A

p.Glu417Lys

p.E417K

P02768

protein_coding

deleterious(0.01)

possibly_damaging(0.476)

TCGA-EK-A3GK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

ALB

SNV

Missense_Mutation

rs267600248

c.628C>T

p.Arg210Trp

p.R210W

P02768

protein_coding

deleterious(0.01)

possibly_damaging(0.883)

TCGA-A6-5665-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

ALB

SNV

Missense_Mutation

rs774294755

c.881N>T

p.Ser294Leu

p.S294L

P02768

protein_coding

tolerated(0.31)

benign(0.041)

TCGA-AA-A00N-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

ALB

SNV

Missense_Mutation

rs150388973

c.946N>A

p.Glu316Lys

p.E316K

P02768

protein_coding

tolerated(0.07)

benign(0.109)

TCGA-AZ-4313-01

Colorectum

colon adenocarcinoma

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
213	ALB	TRANSPORTER, DRUGGABLE GENOME		Sodium lauryl sulfate
213	ALB	TRANSPORTER, DRUGGABLE GENOME		Gadofosveset	GADOFOSVESET
213	ALB	TRANSPORTER, DRUGGABLE GENOME		RALTITREXED	RALTITREXED	15025739
213	ALB	TRANSPORTER, DRUGGABLE GENOME		Activated recombinant FVII-albumin fusion protein
213	ALB	TRANSPORTER, DRUGGABLE GENOME		Oxyphenbutazone	OXYPHENBUTAZONE
213	ALB	TRANSPORTER, DRUGGABLE GENOME		EPIGALOCATECHIN GALLATE	EPIGALOCATECHIN GALLATE	20598557
213	ALB	TRANSPORTER, DRUGGABLE GENOME		PHENYLBUTAZONE	PHENYLBUTAZONE	20869876
213	ALB	TRANSPORTER, DRUGGABLE GENOME		EPIGALLOCATECHIN	EPIGALLOCATECHIN	20598557
213	ALB	TRANSPORTER, DRUGGABLE GENOME		Iodipamide	IODIPAMIDE
213	ALB	TRANSPORTER, DRUGGABLE GENOME		[19F]-HALOPERIDOL	[19F]-HALOPERIDOL

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