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: BLVRA

Gene summary for BLVRA

Gene summary.

Gene information	Species	Human
	Gene symbol	BLVRA
	Gene ID	644
	Gene name	biliverdin reductase A
	Gene Alias	BLVR
	Cytomap	7p13
	Gene Type	protein-coding
	GO ID	GO:0006725
	UniProtAcc	A0A140VJF4

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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
644	BLVRA	LZE2T	Human	Esophagus	ESCC	8.10e-03	7.59e-01	0.082
644	BLVRA	LZE4T	Human	Esophagus	ESCC	1.13e-16	6.27e-01	0.0811
644	BLVRA	LZE5T	Human	Esophagus	ESCC	3.55e-05	5.66e-01	0.0514
644	BLVRA	LZE7T	Human	Esophagus	ESCC	1.45e-07	5.54e-01	0.0667
644	BLVRA	LZE8T	Human	Esophagus	ESCC	1.81e-21	4.39e-01	0.067
644	BLVRA	LZE20T	Human	Esophagus	ESCC	3.02e-09	2.19e-01	0.0662
644	BLVRA	LZE22T	Human	Esophagus	ESCC	1.10e-04	7.59e-01	0.068
644	BLVRA	LZE24T	Human	Esophagus	ESCC	1.87e-20	7.19e-01	0.0596
644	BLVRA	LZE21T	Human	Esophagus	ESCC	1.54e-04	1.73e-01	0.0655
644	BLVRA	LZE6T	Human	Esophagus	ESCC	9.41e-06	5.14e-01	0.0845
644	BLVRA	P1T-E	Human	Esophagus	ESCC	3.42e-09	6.80e-01	0.0875
644	BLVRA	P2T-E	Human	Esophagus	ESCC	1.26e-44	9.17e-01	0.1177
644	BLVRA	P4T-E	Human	Esophagus	ESCC	5.81e-29	7.20e-01	0.1323
644	BLVRA	P5T-E	Human	Esophagus	ESCC	1.98e-12	3.74e-01	0.1327
644	BLVRA	P8T-E	Human	Esophagus	ESCC	4.00e-29	6.37e-01	0.0889
644	BLVRA	P9T-E	Human	Esophagus	ESCC	2.92e-34	9.09e-01	0.1131
644	BLVRA	P10T-E	Human	Esophagus	ESCC	9.06e-18	3.40e-01	0.116
644	BLVRA	P11T-E	Human	Esophagus	ESCC	3.83e-12	8.03e-01	0.1426
644	BLVRA	P12T-E	Human	Esophagus	ESCC	5.25e-64	1.29e+00	0.1122
644	BLVRA	P15T-E	Human	Esophagus	ESCC	1.07e-36	8.29e-01	0.1149

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
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:004670018	Esophagus	ESCC	heterocycle catabolic process	286/8552	445/18723	1.12e-15	7.47e-14	286
GO:004427019	Esophagus	ESCC	cellular nitrogen compound catabolic process	288/8552	451/18723	3.03e-15	1.79e-13	288
GO:001943918	Esophagus	ESCC	aromatic compound catabolic process	295/8552	467/18723	1.09e-14	5.98e-13	295
GO:190136118	Esophagus	ESCC	organic cyclic compound catabolic process	307/8552	495/18723	9.99e-14	4.80e-12	307
GO:00330132	Esophagus	ESCC	tetrapyrrole metabolic process	37/8552	59/18723	6.23e-03	2.29e-02	37
GO:00424401	Esophagus	ESCC	pigment metabolic process	50/8552	84/18723	7.34e-03	2.64e-02	50
GO:00421681	Esophagus	ESCC	heme metabolic process	27/8552	42/18723	1.16e-02	3.90e-02	27
GO:190136111	Liver	Cirrhotic	organic cyclic compound catabolic process	213/4634	495/18723	1.58e-19	3.67e-17	213
GO:001943911	Liver	Cirrhotic	aromatic compound catabolic process	202/4634	467/18723	6.93e-19	1.28e-16	202
GO:004427011	Liver	Cirrhotic	cellular nitrogen compound catabolic process	195/4634	451/18723	2.99e-18	4.94e-16	195
GO:004670011	Liver	Cirrhotic	heterocycle catabolic process	192/4634	445/18723	7.17e-18	1.12e-15	192
GO:0006787	Liver	Cirrhotic	porphyrin-containing compound catabolic process	8/4634	12/18723	2.59e-03	1.53e-02	8
GO:0033015	Liver	Cirrhotic	tetrapyrrole catabolic process	8/4634	12/18723	2.59e-03	1.53e-02	8
GO:0033013	Liver	Cirrhotic	tetrapyrrole metabolic process	24/4634	59/18723	5.06e-03	2.62e-02	24
GO:0042167	Liver	Cirrhotic	heme catabolic process	7/4634	11/18723	7.11e-03	3.41e-02	7
GO:0046149	Liver	Cirrhotic	pigment catabolic process	7/4634	11/18723	7.11e-03	3.41e-02	7
GO:0006778	Liver	Cirrhotic	porphyrin-containing compound metabolic process	20/4634	49/18723	9.60e-03	4.35e-02	20
GO:004427021	Liver	HCC	cellular nitrogen compound catabolic process	303/7958	451/18723	9.76e-27	3.64e-24	303
GO:004670021	Liver	HCC	heterocycle catabolic process	299/7958	445/18723	2.07e-26	7.29e-24	299
GO:190136121	Liver	HCC	organic cyclic compound catabolic process	325/7958	495/18723	6.52e-26	2.18e-23	325

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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

BLVRA

SNV

Missense_Mutation

novel

c.737N>C

p.Val246Ala

p.V246A

P53004

protein_coding

tolerated(0.78)

benign(0.001)

TCGA-A7-A4SD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

BLVRA

SNV

Missense_Mutation

novel

c.173C>A

p.Ser58Tyr

p.S58Y

P53004

protein_coding

deleterious(0)

probably_damaging(0.959)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

BLVRA

SNV

Missense_Mutation

c.704N>G

p.Ser235Cys

p.S235C

P53004

protein_coding

deleterious(0.05)

probably_damaging(0.996)

TCGA-GM-A2D9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

BLVRA

SNV

Missense_Mutation

c.512N>A

p.Ser171Tyr

p.S171Y

P53004

protein_coding

deleterious(0.01)

probably_damaging(0.992)

TCGA-GM-A2DO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

BLVRA

insertion

Nonsense_Mutation

novel

c.428_429insTCCTCCTTGCTCCTGAGGTGCAGGTCAAGCCCAG

p.Lys143AsnfsTer6

p.K143Nfs*6

P53004

protein_coding

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

BLVRA

insertion

Frame_Shift_Ins

novel

c.448_449insCCAC

p.Leu150ProfsTer69

p.L150Pfs*69

P53004

protein_coding

TCGA-BH-A0B8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

BLVRA

insertion

Nonsense_Mutation

novel

c.449_450insGCAATTTCTGCCTCCCAGGTTCTAGTGATTCTCCTG

p.Leu150_Leu151insGlnPheLeuProProArgPheTerTerPheSerCys

p.L150_L151insQFLPPRF**FSC

P53004

protein_coding

TCGA-BH-A0B8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

BLVRA

SNV

Missense_Mutation

rs183114141

c.127G>A

p.Val43Met

p.V43M

P53004

protein_coding

deleterious(0)

possibly_damaging(0.48)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

BLVRA

SNV

Missense_Mutation

c.478N>C

p.Glu160Gln

p.E160Q

P53004

protein_coding

tolerated(0.39)

benign(0.188)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

BLVRA

SNV

Missense_Mutation

rs183114141

c.127N>T

p.Val43Leu

p.V43L

P53004

protein_coding

deleterious(0.02)

benign(0.354)

TCGA-A6-6140-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

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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
644	BLVRA	ENZYME		Ursodeoxycholic acid

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