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: IQGAP2

Gene summary for IQGAP2

Gene summary.

Gene information	Species	Human
	Gene symbol	IQGAP2
	Gene ID	10788
	Gene name	IQ motif containing GTPase activating protein 2
	Gene Alias	IQGAP2
	Cytomap	5q13.3
	Gene Type	protein-coding
	GO ID	GO:0006996
	UniProtAcc	B7Z7U6

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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
10788	IQGAP2	CA_HPV_1	Human	Cervix	CC	1.65e-05	-2.59e-02	0.0264
10788	IQGAP2	CCI_1	Human	Cervix	CC	2.35e-04	-4.88e-01	0.528
10788	IQGAP2	CCII_1	Human	Cervix	CC	1.21e-10	-4.97e-01	0.3249
10788	IQGAP2	Tumor	Human	Cervix	CC	2.00e-29	-5.08e-01	0.1241
10788	IQGAP2	sample1	Human	Cervix	CC	1.32e-05	-4.57e-01	0.0959
10788	IQGAP2	sample3	Human	Cervix	CC	8.06e-30	-5.08e-01	0.1387
10788	IQGAP2	L1	Human	Cervix	CC	2.62e-09	-4.68e-01	0.0802
10788	IQGAP2	T1	Human	Cervix	CC	2.21e-17	-4.80e-01	0.0918
10788	IQGAP2	T3	Human	Cervix	CC	2.08e-31	-5.06e-01	0.1389
10788	IQGAP2	HTA11_3410_2000001011	Human	Colorectum	AD	4.29e-15	-6.36e-01	0.0155
10788	IQGAP2	HTA11_347_2000001011	Human	Colorectum	AD	1.85e-11	6.55e-01	-0.1954
10788	IQGAP2	HTA11_866_3004761011	Human	Colorectum	AD	1.36e-14	-7.03e-01	0.096
10788	IQGAP2	HTA11_9408_2000001011	Human	Colorectum	AD	3.72e-02	-8.37e-01	0.0451
10788	IQGAP2	HTA11_8622_2000001021	Human	Colorectum	SER	4.84e-03	-6.32e-01	0.0528
10788	IQGAP2	HTA11_10711_2000001011	Human	Colorectum	AD	3.07e-06	-5.91e-01	0.0338
10788	IQGAP2	HTA11_7696_3000711011	Human	Colorectum	AD	2.77e-09	-4.63e-01	0.0674
10788	IQGAP2	HTA11_99999970781_79442	Human	Colorectum	MSS	7.09e-31	-7.95e-01	0.294
10788	IQGAP2	HTA11_99999971662_82457	Human	Colorectum	MSS	9.60e-09	-4.65e-01	0.3859
10788	IQGAP2	HTA11_99999973899_84307	Human	Colorectum	MSS	3.84e-11	-8.71e-01	0.2585
10788	IQGAP2	HTA11_99999974143_84620	Human	Colorectum	MSS	1.82e-37	-8.62e-01	0.3005

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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
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Prostate		BPH: Benign Prostatic Hyperplasia
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:005125829	Thyroid	ATC	protein polymerization	159/6293	297/18723	9.33e-13	3.96e-11	159
GO:0110053210	Thyroid	ATC	regulation of actin filament organization	150/6293	278/18723	1.82e-12	7.58e-11	150
GO:0051495111	Thyroid	ATC	positive regulation of cytoskeleton organization	125/6293	226/18723	1.39e-11	5.08e-10	125
GO:190290529	Thyroid	ATC	positive regulation of supramolecular fiber organization	117/6293	209/18723	2.19e-11	7.80e-10	117
GO:003253526	Thyroid	ATC	regulation of cellular component size	191/6293	383/18723	2.51e-11	8.69e-10	191
GO:003227129	Thyroid	ATC	regulation of protein polymerization	127/6293	233/18723	3.64e-11	1.20e-09	127
GO:0008154111	Thyroid	ATC	actin polymerization or depolymerization	119/6293	218/18723	1.32e-10	4.08e-09	119
GO:003133428	Thyroid	ATC	positive regulation of protein-containing complex assembly	127/6293	237/18723	1.64e-10	4.93e-09	127
GO:0008064111	Thyroid	ATC	regulation of actin polymerization or depolymerization	101/6293	188/18723	9.88e-09	2.05e-07	101
GO:0030832111	Thyroid	ATC	regulation of actin filament length	101/6293	189/18723	1.43e-08	2.92e-07	101
GO:0030041111	Thyroid	ATC	actin filament polymerization	101/6293	191/18723	2.91e-08	5.50e-07	101
GO:0032273113	Thyroid	ATC	positive regulation of protein polymerization	77/6293	138/18723	6.67e-08	1.17e-06	77
GO:0030833110	Thyroid	ATC	regulation of actin filament polymerization	91/6293	172/18723	1.34e-07	2.20e-06	91
GO:0031532111	Thyroid	ATC	actin cytoskeleton reorganization	62/6293	107/18723	2.01e-07	3.17e-06	62
GO:004308719	Thyroid	ATC	regulation of GTPase activity	153/6293	348/18723	3.24e-05	2.68e-04	153
GO:0030838110	Thyroid	ATC	positive regulation of actin filament polymerization	52/6293	99/18723	7.88e-05	5.94e-04	52
GO:003431418	Thyroid	ATC	Arp2/3 complex-mediated actin nucleation	24/6293	39/18723	3.25e-04	2.03e-03	24
GO:200024914	Thyroid	ATC	regulation of actin cytoskeleton reorganization	23/6293	39/18723	1.01e-03	5.34e-03	23
GO:004501014	Thyroid	ATC	actin nucleation	28/6293	52/18723	2.08e-03	9.82e-03	28

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0481016	Cervix	CC	Regulation of actin cytoskeleton	64/1267	229/8465	2.24e-07	2.59e-06	1.53e-06	64
hsa0481017	Cervix	CC	Regulation of actin cytoskeleton	64/1267	229/8465	2.24e-07	2.59e-06	1.53e-06	64
hsa04810	Colorectum	AD	Regulation of actin cytoskeleton	75/2092	229/8465	3.36e-03	1.76e-02	1.12e-02	75
hsa048101	Colorectum	AD	Regulation of actin cytoskeleton	75/2092	229/8465	3.36e-03	1.76e-02	1.12e-02	75
hsa048102	Colorectum	SER	Regulation of actin cytoskeleton	60/1580	229/8465	2.74e-03	2.02e-02	1.47e-02	60
hsa048103	Colorectum	SER	Regulation of actin cytoskeleton	60/1580	229/8465	2.74e-03	2.02e-02	1.47e-02	60
hsa048104	Colorectum	MSS	Regulation of actin cytoskeleton	68/1875	229/8465	4.27e-03	1.86e-02	1.14e-02	68
hsa048105	Colorectum	MSS	Regulation of actin cytoskeleton	68/1875	229/8465	4.27e-03	1.86e-02	1.14e-02	68
hsa048106	Colorectum	FAP	Regulation of actin cytoskeleton	65/1404	229/8465	4.07e-06	5.91e-05	3.59e-05	65
hsa048107	Colorectum	FAP	Regulation of actin cytoskeleton	65/1404	229/8465	4.07e-06	5.91e-05	3.59e-05	65
hsa048108	Colorectum	CRC	Regulation of actin cytoskeleton	52/1091	229/8465	2.34e-05	5.57e-04	3.78e-04	52
hsa048109	Colorectum	CRC	Regulation of actin cytoskeleton	52/1091	229/8465	2.34e-05	5.57e-04	3.78e-04	52
hsa0481018	Endometrium	AEH	Regulation of actin cytoskeleton	50/1197	229/8465	9.08e-04	5.78e-03	4.23e-03	50
hsa0481019	Endometrium	AEH	Regulation of actin cytoskeleton	50/1197	229/8465	9.08e-04	5.78e-03	4.23e-03	50
hsa0481024	Endometrium	EEC	Regulation of actin cytoskeleton	49/1237	229/8465	3.20e-03	1.78e-02	1.33e-02	49
hsa0481034	Endometrium	EEC	Regulation of actin cytoskeleton	49/1237	229/8465	3.20e-03	1.78e-02	1.33e-02	49
hsa0481010	Liver	NAFLD	Regulation of actin cytoskeleton	50/1043	229/8465	3.01e-05	7.59e-04	6.11e-04	50
hsa0481011	Liver	NAFLD	Regulation of actin cytoskeleton	50/1043	229/8465	3.01e-05	7.59e-04	6.11e-04	50
hsa0481021	Liver	Cirrhotic	Regulation of actin cytoskeleton	100/2530	229/8465	5.28e-06	5.50e-05	3.39e-05	100
hsa0481031	Liver	Cirrhotic	Regulation of actin cytoskeleton	100/2530	229/8465	5.28e-06	5.50e-05	3.39e-05	100

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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

IQGAP2

SNV

Missense_Mutation

c.3481N>T

p.Leu1161Phe

p.L1161F

Q13576

protein_coding

deleterious(0)

possibly_damaging(0.757)

TCGA-A2-A25E-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

IQGAP2

SNV

Missense_Mutation

novel

c.2327N>T

p.Ser776Phe

p.S776F

Q13576

protein_coding

deleterious(0)

possibly_damaging(0.707)

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

IQGAP2

SNV

Missense_Mutation

c.1039N>A

p.Glu347Lys

p.E347K

Q13576

protein_coding

deleterious(0.05)

probably_damaging(0.992)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

IQGAP2

SNV

Missense_Mutation

novel

c.1718N>T

p.Pro573Leu

p.P573L

Q13576

protein_coding

tolerated(0.14)

benign(0.125)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

IQGAP2

SNV

Missense_Mutation

rs768262402

c.3248N>T

p.Ser1083Leu

p.S1083L

Q13576

protein_coding

deleterious(0.05)

benign(0.34)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

IQGAP2

SNV

Missense_Mutation

c.1474N>G

p.Gln492Glu

p.Q492E

Q13576

protein_coding

tolerated(0.68)

benign(0.007)

TCGA-B6-A0WZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

IQGAP2

SNV

Missense_Mutation

c.50N>A

p.Ile17Asn

p.I17N

Q13576

protein_coding

deleterious(0)

possibly_damaging(0.573)

TCGA-E9-A1NA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

IQGAP2

SNV

Missense_Mutation

novel

c.1166C>T

p.Ser389Phe

p.S389F

Q13576

protein_coding

deleterious(0.04)

benign(0.017)

TCGA-GM-A3NW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

IQGAP2

SNV

Missense_Mutation

rs528370381

c.1442C>T

p.Ala481Val

p.A481V

Q13576

protein_coding

tolerated(0.06)

benign(0.133)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

IQGAP2

SNV

Missense_Mutation

novel

c.3319C>T

p.Arg1107Trp

p.R1107W

Q13576

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-2W-A8YY-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

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