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: HEBP2

Gene summary for HEBP2

Gene summary.

Gene information	Species	Human
	Gene symbol	HEBP2
	Gene ID	23593
	Gene name	heme binding protein 2
	Gene Alias	C6ORF34B
	Cytomap	6q24.1
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	Q5THN1

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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
23593	HEBP2	GSM4909280	Human	Breast	Precancer	2.06e-08	-7.70e-01	0.0305
23593	HEBP2	GSM4909286	Human	Breast	IDC	2.79e-10	3.17e-01	0.1081
23593	HEBP2	GSM4909287	Human	Breast	IDC	3.77e-04	3.00e-01	0.2057
23593	HEBP2	GSM4909289	Human	Breast	IDC	2.73e-15	7.47e-01	0.1064
23593	HEBP2	GSM4909290	Human	Breast	IDC	1.63e-15	5.69e-01	0.2096
23593	HEBP2	GSM4909294	Human	Breast	IDC	2.18e-06	3.59e-02	0.2022
23593	HEBP2	GSM4909296	Human	Breast	IDC	1.12e-32	-6.69e-01	0.1524
23593	HEBP2	GSM4909297	Human	Breast	IDC	9.96e-19	-3.74e-01	0.1517
23593	HEBP2	GSM4909298	Human	Breast	IDC	1.38e-07	3.02e-01	0.1551
23593	HEBP2	GSM4909301	Human	Breast	IDC	4.80e-03	1.82e-01	0.1577
23593	HEBP2	GSM4909302	Human	Breast	IDC	1.67e-04	-3.41e-01	0.1545
23593	HEBP2	GSM4909304	Human	Breast	IDC	2.82e-03	-3.97e-01	0.1636
23593	HEBP2	GSM4909306	Human	Breast	IDC	3.48e-06	2.83e-01	0.1564
23593	HEBP2	GSM4909311	Human	Breast	IDC	1.59e-43	-5.24e-01	0.1534
23593	HEBP2	GSM4909312	Human	Breast	IDC	2.23e-12	-2.96e-01	0.1552
23593	HEBP2	GSM4909315	Human	Breast	IDC	4.71e-50	7.09e-01	0.21
23593	HEBP2	GSM4909316	Human	Breast	IDC	2.87e-11	4.36e-01	0.21
23593	HEBP2	GSM4909317	Human	Breast	IDC	7.36e-04	3.55e-01	0.1355
23593	HEBP2	GSM4909319	Human	Breast	IDC	6.34e-50	-6.24e-01	0.1563
23593	HEBP2	GSM4909320	Human	Breast	IDC	1.73e-07	-5.47e-01	0.1575

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
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
Prostate		BPH: Benign Prostatic Hyperplasia
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:00068398	Breast	Precancer	mitochondrial transport	45/1080	254/18723	1.37e-11	1.88e-09	45
GO:00518816	Breast	Precancer	regulation of mitochondrial membrane potential	18/1080	74/18723	1.45e-07	7.82e-06	18
GO:00070066	Breast	Precancer	mitochondrial membrane organization	20/1080	116/18723	9.88e-06	2.61e-04	20
GO:00905595	Breast	Precancer	regulation of membrane permeability	15/1080	78/18723	3.35e-05	7.29e-04	15
GO:0010917	Breast	Precancer	negative regulation of mitochondrial membrane potential	6/1080	13/18723	4.39e-05	9.40e-04	6
GO:00469025	Breast	Precancer	regulation of mitochondrial membrane permeability	13/1080	63/18723	5.13e-05	1.07e-03	13
GO:0045837	Breast	Precancer	negative regulation of membrane potential	6/1080	14/18723	7.30e-05	1.44e-03	6
GO:0010939	Breast	Precancer	regulation of necrotic cell death	9/1080	42/18723	5.42e-04	6.97e-03	9
GO:00357945	Breast	Precancer	positive regulation of mitochondrial membrane permeability	9/1080	43/18723	6.51e-04	7.99e-03	9
GO:0070265	Breast	Precancer	necrotic cell death	11/1080	62/18723	7.54e-04	9.01e-03	11
GO:19057105	Breast	Precancer	positive regulation of membrane permeability	9/1080	48/18723	1.49e-03	1.54e-02	9
GO:000683913	Breast	IDC	mitochondrial transport	51/1434	254/18723	1.54e-10	1.83e-08	51
GO:005188113	Breast	IDC	regulation of mitochondrial membrane potential	19/1434	74/18723	2.04e-06	8.27e-05	19
GO:00458371	Breast	IDC	negative regulation of membrane potential	7/1434	14/18723	3.23e-05	7.50e-04	7
GO:009055913	Breast	IDC	regulation of membrane permeability	17/1434	78/18723	6.88e-05	1.40e-03	17
GO:000700613	Breast	IDC	mitochondrial membrane organization	21/1434	116/18723	1.78e-04	3.00e-03	21
GO:00109171	Breast	IDC	negative regulation of mitochondrial membrane potential	6/1434	13/18723	2.14e-04	3.45e-03	6
GO:004690213	Breast	IDC	regulation of mitochondrial membrane permeability	14/1434	63/18723	2.37e-04	3.75e-03	14
GO:190571012	Breast	IDC	positive regulation of membrane permeability	11/1434	48/18723	8.22e-04	9.65e-03	11
GO:003579413	Breast	IDC	positive regulation of mitochondrial membrane permeability	10/1434	43/18723	1.25e-03	1.33e-02	10

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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

HEBP2

SNV

Missense_Mutation

novel

c.290N>T

p.Ser97Leu

p.S97L

Q9Y5Z4

protein_coding

deleterious(0.04)

benign(0.062)

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HEBP2

SNV

Missense_Mutation

novel

c.140N>G

p.Lys47Arg

p.K47R

Q9Y5Z4

protein_coding

tolerated(0.12)

benign(0.009)

TCGA-AA-3984-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

HEBP2

SNV

Missense_Mutation

novel

c.245N>C

p.Lys82Thr

p.K82T

Q9Y5Z4

protein_coding

deleterious(0.04)

possibly_damaging(0.621)

TCGA-AZ-4315-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

HEBP2

SNV

Missense_Mutation

rs768098976

c.508N>A

p.Asp170Asn

p.D170N

Q9Y5Z4

protein_coding

tolerated(0.52)

benign(0.003)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

HEBP2

SNV

Missense_Mutation

rs750449654

c.613N>A

p.Glu205Lys

p.E205K

Q9Y5Z4

protein_coding

tolerated_low_confidence(0.12)

benign(0)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

HEBP2

SNV

Missense_Mutation

novel

c.450N>T

p.Lys150Asn

p.K150N

Q9Y5Z4

protein_coding

tolerated(0.07)

probably_damaging(0.99)

TCGA-A5-A2K5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

HEBP2

SNV

Missense_Mutation

rs535510705

c.277G>A

p.Val93Met

p.V93M

Q9Y5Z4

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-AJ-A3EK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

HEBP2

SNV

Missense_Mutation

novel

c.229N>C

p.Asn77His

p.N77H

Q9Y5Z4

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AX-A06F-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

HEBP2

SNV

Missense_Mutation

rs768098976

c.508N>A

p.Asp170Asn

p.D170N

Q9Y5Z4

protein_coding

tolerated(0.52)

benign(0.003)

TCGA-B5-A0JY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

HEBP2

SNV

Missense_Mutation

novel

c.450N>T

p.Lys150Asn

p.K150N

Q9Y5Z4

protein_coding

tolerated(0.07)

probably_damaging(0.99)

TCGA-BK-A6W3-01

Endometrium

uterine corpus endometrioid carcinoma

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

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