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	CCI_1	Human	Cervix	CC	8.07e-18	1.95e+00	0.528
10644	IGF2BP2	CCI_2	Human	Cervix	CC	1.49e-25	2.21e+00	0.5249
10644	IGF2BP2	sample3	Human	Cervix	CC	1.32e-13	2.54e-01	0.1387
10644	IGF2BP2	H2	Human	Cervix	HSIL_HPV	4.26e-03	2.33e-01	0.0632
10644	IGF2BP2	T1	Human	Cervix	CC	2.72e-09	4.41e-01	0.0918
10644	IGF2BP2	T2	Human	Cervix	CC	1.68e-02	3.32e-01	0.0709
10644	IGF2BP2	T3	Human	Cervix	CC	7.74e-04	2.30e-01	0.1389
10644	IGF2BP2	HTA11_3410_2000001011	Human	Colorectum	AD	4.96e-22	-6.91e-01	0.0155
10644	IGF2BP2	HTA11_3361_2000001011	Human	Colorectum	AD	3.34e-05	-5.75e-01	-0.1207
10644	IGF2BP2	HTA11_9341_2000001011	Human	Colorectum	SER	3.98e-04	-7.71e-01	-0.00410000000000005
10644	IGF2BP2	HTA11_7862_2000001011	Human	Colorectum	AD	7.94e-04	-5.26e-01	-0.0179
10644	IGF2BP2	HTA11_866_3004761011	Human	Colorectum	AD	2.54e-17	-5.80e-01	0.096
10644	IGF2BP2	HTA11_8622_2000001021	Human	Colorectum	SER	4.66e-03	-5.29e-01	0.0528
10644	IGF2BP2	HTA11_10623_2000001011	Human	Colorectum	AD	2.14e-02	-4.33e-01	-0.0177
10644	IGF2BP2	HTA11_10711_2000001011	Human	Colorectum	AD	6.75e-12	-6.02e-01	0.0338
10644	IGF2BP2	HTA11_7696_3000711011	Human	Colorectum	AD	3.22e-02	-3.10e-01	0.0674
10644	IGF2BP2	HTA11_6818_2000001011	Human	Colorectum	AD	2.14e-04	-4.91e-01	0.0112
10644	IGF2BP2	HTA11_99999973899_84307	Human	Colorectum	MSS	2.30e-08	-6.32e-01	0.2585
10644	IGF2BP2	HTA11_99999974143_84620	Human	Colorectum	MSS	5.17e-59	-1.11e+00	0.3005
10644	IGF2BP2	F007	Human	Colorectum	FAP	8.81e-08	-5.06e-01	0.1176

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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

novel

c.487G>A

p.Asp163Asn

p.D163N

protein_coding

deleterious(0.03)

possibly_damaging(0.868)

TCGA-AJ-A3EK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

IGF2BP2

SNV

Missense_Mutation

c.740N>A

p.Pro247His

p.P247H

protein_coding

deleterious(0)

probably_damaging(0.976)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

IGF2BP2

SNV

Missense_Mutation

rs200027200

c.1126N>A

p.Ala376Thr

p.A376T

protein_coding

deleterious(0.02)

possibly_damaging(0.864)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

IGF2BP2

SNV

Missense_Mutation

novel

c.755N>T

p.Ala252Val

p.A252V

protein_coding

deleterious(0.02)

possibly_damaging(0.457)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

IGF2BP2

SNV

Missense_Mutation

rs772894965

c.1807C>T

p.Arg603Cys

p.R603C

protein_coding

deleterious_low_confidence(0.02)

benign(0.001)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

IGF2BP2

SNV

Missense_Mutation

novel

c.242N>A

p.Ser81Asn

p.S81N

protein_coding

deleterious(0.03)

possibly_damaging(0.908)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

IGF2BP2

SNV

Missense_Mutation

novel

c.1051C>A

p.Leu351Met

p.L351M

protein_coding

deleterious(0)

probably_damaging(0.965)

TCGA-AX-A06F-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

IGF2BP2

SNV

Missense_Mutation

c.1521N>A

p.Phe507Leu

p.F507L

protein_coding

deleterious(0.02)

benign(0.075)

TCGA-AX-A0J0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

IGF2BP2

SNV

Missense_Mutation

novel

c.613C>A

p.Leu205Met

p.L205M

protein_coding

deleterious(0.01)

probably_damaging(0.988)

TCGA-AX-A0J1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

IGF2BP2

SNV

Missense_Mutation

novel

c.425C>T

p.Ala142Val

p.A142V

protein_coding

deleterious(0)

probably_damaging(0.983)

TCGA-AX-A0J1-01

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
10644	IGF2BP2	NA		repaglinide	REPAGLINIDE

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