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: IGFBP7

Gene summary for IGFBP7

Gene summary.

Gene information	Species	Human
	Gene symbol	IGFBP7
	Gene ID	3490
	Gene name	insulin like growth factor binding protein 7
	Gene Alias	AGM
	Cytomap	4q12
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q16270

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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
3490	IGFBP7	GSM4909281	Human	Breast	IDC	8.49e-23	5.98e-01	0.21
3490	IGFBP7	GSM4909282	Human	Breast	IDC	6.27e-06	2.57e-01	-0.0288
3490	IGFBP7	GSM4909286	Human	Breast	IDC	2.03e-06	2.35e-01	0.1081
3490	IGFBP7	GSM4909287	Human	Breast	IDC	1.76e-03	2.62e-01	0.2057
3490	IGFBP7	GSM4909301	Human	Breast	IDC	7.43e-04	-1.79e-01	0.1577
3490	IGFBP7	GSM4909304	Human	Breast	IDC	7.43e-04	-1.73e-01	0.1636
3490	IGFBP7	GSM4909312	Human	Breast	IDC	1.57e-03	-1.79e-01	0.1552
3490	IGFBP7	GSM4909315	Human	Breast	IDC	7.79e-05	-1.79e-01	0.21
3490	IGFBP7	GSM4909321	Human	Breast	IDC	7.43e-04	-1.79e-01	0.1559
3490	IGFBP7	brca10	Human	Breast	Precancer	2.43e-15	5.56e-01	-0.0029
3490	IGFBP7	CA_HPV_3	Human	Cervix	CC	1.64e-03	-1.01e-01	0.0414
3490	IGFBP7	CCI_1	Human	Cervix	CC	1.04e-03	-5.65e-01	0.528
3490	IGFBP7	CCII_1	Human	Cervix	CC	1.59e-09	-5.75e-01	0.3249
3490	IGFBP7	sample1	Human	Cervix	CC	2.23e-07	6.79e-01	0.0959
3490	IGFBP7	L1	Human	Cervix	CC	1.21e-04	-2.81e-01	0.0802
3490	IGFBP7	T1	Human	Cervix	CC	5.07e-13	6.01e-01	0.0918
3490	IGFBP7	AEH-subject1	Human	Endometrium	AEH	4.60e-10	-4.86e-01	-0.3059
3490	IGFBP7	AEH-subject2	Human	Endometrium	AEH	1.09e-11	-5.98e-01	-0.2525
3490	IGFBP7	AEH-subject5	Human	Endometrium	AEH	7.17e-28	-9.00e-01	-0.2953
3490	IGFBP7	EEC-subject1	Human	Endometrium	EEC	1.18e-41	-9.84e-01	-0.2682

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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
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:00485459	Breast	Precancer	response to steroid hormone	53/1080	339/18723	3.07e-11	3.66e-09	53
GO:00319608	Breast	Precancer	response to corticosteroid	30/1080	167/18723	2.50e-08	1.65e-06	30
GO:00513848	Breast	Precancer	response to glucocorticoid	26/1080	148/18723	3.32e-07	1.57e-05	26
GO:00075653	Breast	Precancer	female pregnancy	29/1080	193/18723	2.07e-06	7.31e-05	29
GO:00447063	Breast	Precancer	multi-multicellular organism process	31/1080	220/18723	3.73e-06	1.19e-04	31
GO:00092667	Breast	Precancer	response to temperature stimulus	27/1080	178/18723	3.85e-06	1.21e-04	27
GO:00094088	Breast	Precancer	response to heat	18/1080	110/18723	5.57e-05	1.15e-03	18
GO:00075663	Breast	Precancer	embryo implantation	11/1080	53/18723	1.82e-04	2.95e-03	11
GO:00160497	Breast	Precancer	cell growth	46/1080	482/18723	5.63e-04	7.16e-03	46
GO:00192164	Breast	Precancer	regulation of lipid metabolic process	34/1080	331/18723	8.14e-04	9.55e-03	34
GO:00015587	Breast	Precancer	regulation of cell growth	39/1080	414/18723	1.81e-03	1.78e-02	39
GO:19016549	Breast	Precancer	response to ketone	22/1080	194/18723	1.89e-03	1.84e-02	22
GO:00973058	Breast	Precancer	response to alcohol	25/1080	253/18723	6.16e-03	4.35e-02	25
GO:004854514	Breast	IDC	response to steroid hormone	70/1434	339/18723	1.34e-14	4.23e-12	70
GO:003196013	Breast	IDC	response to corticosteroid	37/1434	167/18723	3.10e-09	2.63e-07	37
GO:000756511	Breast	IDC	female pregnancy	39/1434	193/18723	1.81e-08	1.27e-06	39
GO:005138413	Breast	IDC	response to glucocorticoid	32/1434	148/18723	6.52e-08	4.07e-06	32
GO:00447061	Breast	IDC	multi-multicellular organism process	41/1434	220/18723	8.58e-08	5.19e-06	41
GO:000926612	Breast	IDC	response to temperature stimulus	34/1434	178/18723	5.88e-07	2.83e-05	34
GO:190165414	Breast	IDC	response to ketone	33/1434	194/18723	1.17e-05	3.13e-04	33

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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

IGFBP7

deletion

Frame_Shift_Del

novel

c.665delN

p.Gly222ValfsTer8

p.G222Vfs*8

Q16270

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

IGFBP7

SNV

Missense_Mutation

novel

c.730G>A

p.Gly244Arg

p.G244R

Q16270

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-VS-A8QC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

paclitaxel

IGFBP7

SNV

Missense_Mutation

rs146423345

c.637N>T

p.Arg213Trp

p.R213W

Q16270

protein_coding

deleterious(0)

probably_damaging(0.991)

TCGA-AA-3815-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

IGFBP7

SNV

Missense_Mutation

c.610C>A

p.Gln204Lys

p.Q204K

Q16270

protein_coding

tolerated(0.35)

benign(0.031)

TCGA-CA-6718-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

IGFBP7

SNV

Missense_Mutation

c.497N>A

p.Pro166His

p.P166H

Q16270

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A5-A0GA-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Chemotherapy

taxol

IGFBP7

SNV

Missense_Mutation

c.743N>C

p.Cys248Ser

p.C248S

Q16270

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A5-A0GM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

IGFBP7

SNV

Missense_Mutation

c.748N>A

p.Ala250Thr

p.A250T

Q16270

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AX-A0J1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

IGFBP7

SNV

Missense_Mutation

c.813N>C

p.Glu271Asp

p.E271D

Q16270

protein_coding

tolerated_low_confidence(0.48)

benign(0.014)

TCGA-B5-A0JY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

IGFBP7

SNV

Missense_Mutation

c.520G>A

p.Gly174Ser

p.G174S

Q16270

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-B5-A11W-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

IGFBP7

SNV

Missense_Mutation

novel

c.585N>T

p.Lys195Asn

p.K195N

Q16270

protein_coding

deleterious(0)

probably_damaging(0.918)

TCGA-B5-A1MX-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Hormone Therapy

megace

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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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