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: IGF2BP2

Gene summary for IGF2BP2

Gene summary.

Gene information	Species	Human
	Gene symbol	IGF2BP2
	Gene ID	10644
	Gene name	insulin like growth factor 2 mRNA binding protein 2
	Gene Alias	IMP-2
	Cytomap	3q27.2
	Gene Type	protein-coding
	GO ID	GO:0001816
	UniProtAcc	Q9Y6M1

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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
10644	IGF2BP2	RNA-P3T-P3T-4	Human	Lung	IAC	4.11e-06	4.13e-01	0.1859
10644	IGF2BP2	RNA-P7T1-P7T1-1	Human	Lung	AIS	3.94e-06	6.21e-01	-0.0961
10644	IGF2BP2	RNA-P7T1-P7T1-2	Human	Lung	AIS	1.76e-14	8.75e-01	-0.0876
10644	IGF2BP2	RNA-P7T1-P7T1-3	Human	Lung	AIS	1.49e-08	7.97e-01	-0.0822
10644	IGF2BP2	RNA-P7T1-P7T1-4	Human	Lung	AIS	2.15e-12	8.21e-01	-0.0809
10644	IGF2BP2	C04	Human	Oral cavity	OSCC	6.24e-23	1.21e+00	0.2633
10644	IGF2BP2	C21	Human	Oral cavity	OSCC	1.20e-75	2.04e+00	0.2678
10644	IGF2BP2	C30	Human	Oral cavity	OSCC	7.20e-54	2.30e+00	0.3055
10644	IGF2BP2	C38	Human	Oral cavity	OSCC	3.33e-26	2.09e+00	0.172
10644	IGF2BP2	C46	Human	Oral cavity	OSCC	3.44e-03	1.67e-01	0.1673
10644	IGF2BP2	C51	Human	Oral cavity	OSCC	7.97e-07	5.56e-01	0.2674
10644	IGF2BP2	C06	Human	Oral cavity	OSCC	1.32e-05	1.47e+00	0.2699
10644	IGF2BP2	C07	Human	Oral cavity	OSCC	2.28e-02	3.21e-01	0.2491
10644	IGF2BP2	C08	Human	Oral cavity	OSCC	7.03e-55	1.27e+00	0.1919
10644	IGF2BP2	C09	Human	Oral cavity	OSCC	1.99e-11	4.38e-01	0.1431
10644	IGF2BP2	LN22	Human	Oral cavity	OSCC	1.10e-06	8.45e-01	0.1733
10644	IGF2BP2	LN38	Human	Oral cavity	OSCC	1.59e-14	1.86e+00	0.168
10644	IGF2BP2	NEOLP-3	Human	Oral cavity	NEOLP	2.92e-03	3.27e-01	-0.0191
10644	IGF2BP2	SYSMH1	Human	Oral cavity	OSCC	1.15e-61	1.28e+00	0.1127
10644	IGF2BP2	SYSMH2	Human	Oral cavity	OSCC	8.05e-15	6.92e-01	0.2326

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
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
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:000641710	Cervix	CC	regulation of translation	89/2311	468/18723	1.86e-05	3.46e-04	89
GO:00512368	Cervix	CC	establishment of RNA localization	39/2311	166/18723	4.76e-05	7.25e-04	39
GO:00506578	Cervix	CC	nucleic acid transport	38/2311	163/18723	7.06e-05	9.85e-04	38
GO:00506588	Cervix	CC	RNA transport	38/2311	163/18723	7.06e-05	9.85e-04	38
GO:000640310	Cervix	CC	RNA localization	43/2311	201/18723	2.00e-04	2.29e-03	43
GO:00510284	Cervix	CC	mRNA transport	31/2311	130/18723	2.05e-04	2.33e-03	31
GO:00159318	Cervix	CC	nucleobase-containing compound transport	43/2311	222/18723	1.72e-03	1.30e-02	43
GO:000641715	Cervix	HSIL_HPV	regulation of translation	34/737	468/18723	4.66e-04	6.83e-03	34
GO:0006417	Colorectum	AD	regulation of translation	141/3918	468/18723	1.32e-06	4.22e-05	141
GO:0006403	Colorectum	AD	RNA localization	71/3918	201/18723	1.54e-06	4.76e-05	71
GO:0051236	Colorectum	AD	establishment of RNA localization	58/3918	166/18723	1.95e-05	4.01e-04	58
GO:0015931	Colorectum	AD	nucleobase-containing compound transport	73/3918	222/18723	2.02e-05	4.10e-04	73
GO:0050657	Colorectum	AD	nucleic acid transport	57/3918	163/18723	2.22e-05	4.39e-04	57
GO:0050658	Colorectum	AD	RNA transport	57/3918	163/18723	2.22e-05	4.39e-04	57
GO:0051028	Colorectum	AD	mRNA transport	42/3918	130/18723	1.57e-03	1.32e-02	42
GO:00064031	Colorectum	SER	RNA localization	53/2897	201/18723	4.51e-05	1.13e-03	53
GO:00159311	Colorectum	SER	nucleobase-containing compound transport	54/2897	222/18723	3.65e-04	5.67e-03	54
GO:00064171	Colorectum	SER	regulation of translation	100/2897	468/18723	3.76e-04	5.74e-03	100
GO:00512361	Colorectum	SER	establishment of RNA localization	42/2897	166/18723	6.70e-04	8.96e-03	42
GO:00506571	Colorectum	SER	nucleic acid transport	41/2897	163/18723	8.74e-04	1.06e-02	41

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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

IGF2BP2

SNV

Missense_Mutation

rs140669105

c.1124N>A

p.Ser375Asn

p.S375N

protein_coding

tolerated(0.8)

benign(0.003)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

IGF2BP2

SNV

Missense_Mutation

c.1382G>A

p.Arg461Lys

p.R461K

protein_coding

tolerated(0.08)

benign(0.418)

TCGA-BH-A2L8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

IGF2BP2

SNV

Missense_Mutation

c.113C>A

p.Ser38Tyr

p.S38Y

protein_coding

deleterious(0.02)

possibly_damaging(0.844)

TCGA-EW-A1PE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

IGF2BP2

insertion

Frame_Shift_Ins

novel

c.430_431insTTCAAGTTGTAGC

p.Glu144ValfsTer13

p.E144Vfs*13

protein_coding

TCGA-A2-A0CT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

IGF2BP2

insertion

Frame_Shift_Ins

novel

c.844_845insTCCACCACAGTGTGTTGGGAGG

p.Pro282LeufsTer33

p.P282Lfs*33

protein_coding

TCGA-AO-A0J4-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

IGF2BP2

insertion

Frame_Shift_Ins

novel

c.984_985insGAGAGATATATATCTACATACATACATGTGCA

p.Arg329GlufsTer16

p.R329Efs*16

protein_coding

TCGA-BH-A0B8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

IGF2BP2

deletion

Frame_Shift_Del

c.515delN

p.Pro172LeufsTer49

p.P172Lfs*49

protein_coding

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

IGF2BP2

deletion

Frame_Shift_Del

novel

c.1655delN

p.Pro552LeufsTer12

p.P552Lfs*12

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

IGF2BP2

SNV

Missense_Mutation

c.1382N>A

p.Arg461Lys

p.R461K

protein_coding

tolerated(0.08)

benign(0.418)

TCGA-Q1-A6DW-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

IGF2BP2

SNV

Missense_Mutation

novel

c.126N>A

p.Phe42Leu

p.F42L

protein_coding

deleterious(0)

possibly_damaging(0.854)

TCGA-VS-A8EI-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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
10644	IGF2BP2	NA		repaglinide	REPAGLINIDE

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