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:005105610	Esophagus	ESCC	regulation of small GTPase mediated signal transduction	157/8552	302/18723	1.55e-02	4.98e-02	157
GO:000989612	Liver	Cirrhotic	positive regulation of catabolic process	215/4634	492/18723	1.13e-20	3.56e-18	215
GO:003133112	Liver	Cirrhotic	positive regulation of cellular catabolic process	190/4634	427/18723	1.94e-19	4.18e-17	190
GO:001623611	Liver	Cirrhotic	macroautophagy	129/4634	291/18723	1.75e-13	1.41e-11	129
GO:004325412	Liver	Cirrhotic	regulation of protein-containing complex assembly	169/4634	428/18723	7.40e-12	4.99e-10	169
GO:005109812	Liver	Cirrhotic	regulation of binding	148/4634	363/18723	9.14e-12	5.97e-10	148
GO:001050611	Liver	Cirrhotic	regulation of autophagy	132/4634	317/18723	2.17e-11	1.33e-09	132
GO:004259412	Liver	Cirrhotic	response to starvation	87/4634	197/18723	1.85e-09	7.78e-08	87
GO:003166712	Liver	Cirrhotic	response to nutrient levels	174/4634	474/18723	3.08e-09	1.27e-07	174
GO:00070332	Liver	Cirrhotic	vacuole organization	80/4634	180/18723	5.73e-09	2.25e-07	80
GO:007149612	Liver	Cirrhotic	cellular response to external stimulus	123/4634	320/18723	3.27e-08	1.10e-06	123
GO:004339312	Liver	Cirrhotic	regulation of protein binding	83/4634	196/18723	4.44e-08	1.42e-06	83
GO:000963612	Liver	Cirrhotic	response to toxic substance	104/4634	262/18723	5.63e-08	1.74e-06	104
GO:005109912	Liver	Cirrhotic	positive regulation of binding	74/4634	173/18723	1.44e-07	3.87e-06	74
GO:00316686	Liver	Cirrhotic	cellular response to extracellular stimulus	96/4634	246/18723	4.55e-07	1.05e-05	96
GO:00092675	Liver	Cirrhotic	cellular response to starvation	67/4634	156/18723	4.58e-07	1.05e-05	67
GO:00316695	Liver	Cirrhotic	cellular response to nutrient levels	85/4634	215/18723	1.08e-06	2.20e-05	85
GO:00108216	Liver	Cirrhotic	regulation of mitochondrion organization	62/4634	144/18723	1.09e-06	2.22e-05	62
GO:003209211	Liver	Cirrhotic	positive regulation of protein binding	41/4634	85/18723	2.28e-06	4.19e-05	41
GO:00162414	Liver	Cirrhotic	regulation of macroautophagy	60/4634	141/18723	2.57e-06	4.63e-05	60

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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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