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:005123616	Esophagus	HGIN	establishment of RNA localization	49/2587	166/18723	1.07e-07	5.47e-06	49
GO:00510288	Esophagus	HGIN	mRNA transport	40/2587	130/18723	4.67e-07	2.07e-05	40
GO:001593116	Esophagus	HGIN	nucleobase-containing compound transport	57/2587	222/18723	1.76e-06	6.52e-05	57
GO:00342496	Esophagus	HGIN	negative regulation of cellular amide metabolic process	66/2587	273/18723	2.74e-06	9.60e-05	66
GO:00171486	Esophagus	HGIN	negative regulation of translation	59/2587	245/18723	1.03e-05	2.96e-04	59
GO:0006403110	Esophagus	ESCC	RNA localization	166/8552	201/18723	1.95e-27	6.18e-25	166
GO:005123617	Esophagus	ESCC	establishment of RNA localization	134/8552	166/18723	1.23e-20	1.81e-18	134
GO:005102815	Esophagus	ESCC	mRNA transport	110/8552	130/18723	2.76e-20	3.80e-18	110
GO:005065717	Esophagus	ESCC	nucleic acid transport	131/8552	163/18723	6.94e-20	8.46e-18	131
GO:005065817	Esophagus	ESCC	RNA transport	131/8552	163/18723	6.94e-20	8.46e-18	131
GO:0006417111	Esophagus	ESCC	regulation of translation	304/8552	468/18723	1.53e-17	1.33e-15	304
GO:001593117	Esophagus	ESCC	nucleobase-containing compound transport	162/8552	222/18723	9.87e-17	7.93e-15	162
GO:003424914	Esophagus	ESCC	negative regulation of cellular amide metabolic process	144/8552	273/18723	1.08e-02	3.67e-02	144
GO:000641712	Liver	Cirrhotic	regulation of translation	194/4634	468/18723	7.28e-16	8.79e-14	194
GO:000640312	Liver	Cirrhotic	RNA localization	94/4634	201/18723	8.57e-12	5.66e-10	94
GO:005123611	Liver	Cirrhotic	establishment of RNA localization	71/4634	166/18723	2.56e-07	6.41e-06	71
GO:00506576	Liver	Cirrhotic	nucleic acid transport	69/4634	163/18723	5.97e-07	1.30e-05	69
GO:00506586	Liver	Cirrhotic	RNA transport	69/4634	163/18723	5.97e-07	1.30e-05	69
GO:00159316	Liver	Cirrhotic	nucleobase-containing compound transport	87/4634	222/18723	1.25e-06	2.52e-05	87
GO:00510282	Liver	Cirrhotic	mRNA transport	56/4634	130/18723	3.47e-06	5.97e-05	56

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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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