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: GTF2I

Gene summary for GTF2I

Gene summary.

Gene information	Species	Human
	Gene symbol	GTF2I
	Gene ID	2969
	Gene name	general transcription factor IIi
	Gene Alias	BAP135
	Cytomap	7q11.23
	Gene Type	protein-coding
	GO ID	GO:0001525
	UniProtAcc	A8K9W7

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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
2969	GTF2I	CA_HPV_1	Human	Cervix	CC	2.66e-07	-2.04e-01	0.0264
2969	GTF2I	N_HPV_1	Human	Cervix	N_HPV	1.10e-03	-3.01e-01	0.0079
2969	GTF2I	CCI_1	Human	Cervix	CC	3.26e-05	6.67e-01	0.528
2969	GTF2I	CCI_2	Human	Cervix	CC	3.03e-16	9.55e-01	0.5249
2969	GTF2I	CCII_1	Human	Cervix	CC	1.52e-04	-4.49e-01	0.3249
2969	GTF2I	L1	Human	Cervix	CC	1.14e-06	-2.80e-01	0.0802
2969	GTF2I	HTA11_3410_2000001011	Human	Colorectum	AD	1.31e-16	-5.89e-01	0.0155
2969	GTF2I	HTA11_2487_2000001011	Human	Colorectum	SER	1.93e-05	-5.28e-01	-0.1808
2969	GTF2I	HTA11_1938_2000001011	Human	Colorectum	AD	2.41e-04	-3.28e-01	-0.0811
2969	GTF2I	HTA11_78_2000001011	Human	Colorectum	AD	4.07e-05	-4.25e-01	-0.1088
2969	GTF2I	HTA11_3361_2000001011	Human	Colorectum	AD	2.21e-10	-6.13e-01	-0.1207
2969	GTF2I	HTA11_866_2000001011	Human	Colorectum	AD	2.77e-10	-4.19e-01	-0.1001
2969	GTF2I	HTA11_2992_2000001011	Human	Colorectum	SER	4.65e-03	-6.42e-01	-0.1706
2969	GTF2I	HTA11_5212_2000001011	Human	Colorectum	AD	9.15e-07	-7.83e-01	-0.2061
2969	GTF2I	HTA11_5216_2000001011	Human	Colorectum	SER	1.08e-02	-6.17e-01	-0.1462
2969	GTF2I	HTA11_7862_2000001011	Human	Colorectum	AD	6.92e-06	-5.81e-01	-0.0179
2969	GTF2I	HTA11_866_3004761011	Human	Colorectum	AD	1.65e-09	-4.52e-01	0.096
2969	GTF2I	HTA11_6801_2000001011	Human	Colorectum	SER	2.58e-02	-6.83e-01	0.0171
2969	GTF2I	HTA11_7696_3000711011	Human	Colorectum	AD	1.10e-08	-3.95e-01	0.0674
2969	GTF2I	HTA11_6818_2000001021	Human	Colorectum	AD	7.76e-06	-5.55e-01	0.0588

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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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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:19013423	Cervix	CC	regulation of vasculature development	60/2311	348/18723	4.48e-03	2.72e-02	60
GO:00457653	Cervix	CC	regulation of angiogenesis	59/2311	342/18723	4.73e-03	2.83e-02	59
GO:00902578	Cervix	CC	regulation of muscle system process	45/2311	252/18723	6.73e-03	3.70e-02	45
GO:00435024	Cervix	CC	regulation of muscle adaptation	21/2311	98/18723	7.71e-03	4.09e-02	21
GO:004576521	Cervix	N_HPV	regulation of angiogenesis	25/534	342/18723	1.80e-05	5.30e-04	25
GO:190134221	Cervix	N_HPV	regulation of vasculature development	25/534	348/18723	2.41e-05	6.66e-04	25
GO:00725031	Cervix	N_HPV	cellular divalent inorganic cation homeostasis	24/534	486/18723	6.76e-03	4.52e-02	24
GO:0090257	Colorectum	AD	regulation of muscle system process	73/3918	252/18723	1.46e-03	1.24e-02	73
GO:0043502	Colorectum	AD	regulation of muscle adaptation	31/3918	98/18723	8.45e-03	4.94e-02	31
GO:00902572	Colorectum	MSS	regulation of muscle system process	66/3467	252/18723	1.55e-03	1.41e-02	66
GO:00030121	Colorectum	MSS	muscle system process	105/3467	452/18723	6.39e-03	4.26e-02	105
GO:00902574	Colorectum	FAP	regulation of muscle system process	58/2622	252/18723	7.22e-05	1.33e-03	58
GO:00030122	Colorectum	FAP	muscle system process	89/2622	452/18723	4.63e-04	5.39e-03	89
GO:00435022	Colorectum	FAP	regulation of muscle adaptation	26/2622	98/18723	7.75e-04	8.17e-03	26
GO:00435001	Colorectum	FAP	muscle adaptation	28/2622	121/18723	4.50e-03	3.06e-02	28
GO:00902575	Colorectum	CRC	regulation of muscle system process	51/2078	252/18723	1.49e-05	4.63e-04	51
GO:00030123	Colorectum	CRC	muscle system process	74/2078	452/18723	3.92e-04	5.80e-03	74
GO:00435023	Colorectum	CRC	regulation of muscle adaptation	21/2078	98/18723	2.22e-03	2.16e-02	21
GO:00030126	Endometrium	AEH	muscle system process	78/2100	452/18723	6.89e-05	1.06e-03	78
GO:00902579	Endometrium	AEH	regulation of muscle system process	44/2100	252/18723	1.92e-03	1.51e-02	44

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04022	Colorectum	MSS	cGMP-PKG signaling pathway	51/1875	167/8465	6.83e-03	2.73e-02	1.67e-02	51
hsa040221	Colorectum	MSS	cGMP-PKG signaling pathway	51/1875	167/8465	6.83e-03	2.73e-02	1.67e-02	51
hsa040222	Colorectum	FAP	cGMP-PKG signaling pathway	42/1404	167/8465	2.84e-03	1.27e-02	7.70e-03	42
hsa040223	Colorectum	FAP	cGMP-PKG signaling pathway	42/1404	167/8465	2.84e-03	1.27e-02	7.70e-03	42
hsa030222	Esophagus	ESCC	Basal transcription factors	35/4205	45/8465	1.01e-04	4.06e-04	2.08e-04	35
hsa0302211	Esophagus	ESCC	Basal transcription factors	35/4205	45/8465	1.01e-04	4.06e-04	2.08e-04	35
hsa03022	Oral cavity	OSCC	Basal transcription factors	28/3704	45/8465	9.53e-03	2.11e-02	1.08e-02	28
hsa030221	Oral cavity	OSCC	Basal transcription factors	28/3704	45/8465	9.53e-03	2.11e-02	1.08e-02	28
hsa040224	Oral cavity	EOLP	cGMP-PKG signaling pathway	36/1218	167/8465	7.34e-03	2.12e-02	1.25e-02	36
hsa0402211	Oral cavity	EOLP	cGMP-PKG signaling pathway	36/1218	167/8465	7.34e-03	2.12e-02	1.25e-02	36

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
GTF2I	CD8TEXP	Liver	HCC	HOPX,TMEM127,TRIM28, etc.	4.34e-03
GTF2I	CD8TEFF	Liver	HCC	HOPX,TMEM127,TRIM28, etc.	9.04e-03
GTF2I	CD8TEXINT	Liver	Healthy	HOPX,TMEM127,TRIM28, etc.	0.00e+00
GTF2I	CD4TN	Liver	Healthy	HOPX,TMEM127,TRIM28, etc.	0.00e+00
GTF2I	TREG	Liver	Healthy	HOPX,TMEM127,TRIM28, etc.	-2.22e-16
GTF2I	BMEM	Liver	NAFLD	HOPX,TMEM127,TRIM28, etc.	0.00e+00
GTF2I	M1MAC	Lung	AIS	BRWD3,ZCCHC17,PHLDA2, etc.	4.17e-02
GTF2I	M2MAC	Lung	AIS	BRWD3,ZCCHC17,PHLDA2, etc.	6.11e-02
GTF2I	NEUT	Lung	AIS	BRWD3,ZCCHC17,PHLDA2, etc.	1.01e-02

∗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

GTF2I

SNV

Missense_Mutation

novel

c.127G>A

p.Glu43Lys

p.E43K

P78347

protein_coding

deleterious(0)

probably_damaging(0.955)

TCGA-A8-A07U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

GTF2I

SNV

Missense_Mutation

novel

c.403C>A

p.Pro135Thr

p.P135T

P78347

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A8-A08R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

GTF2I

SNV

Missense_Mutation

novel

c.2795C>G

p.Ser932Cys

p.S932C

P78347

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-D8-A1JH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

nolvadex

GTF2I

SNV

Missense_Mutation

novel

c.161T>C

p.Val54Ala

p.V54A

P78347

protein_coding

deleterious(0.01)

probably_damaging(0.93)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

GTF2I

SNV

Missense_Mutation

novel

c.1351N>T

p.Pro451Ser

p.P451S

P78347

protein_coding

tolerated(0.16)

probably_damaging(0.986)

TCGA-E2-A15H-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

herceptin

GTF2I

SNV

Missense_Mutation

rs782059244

c.1288N>T

p.Arg430Cys

p.R430C

P78347

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-E2-A576-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

taxotere

GTF2I

SNV

Missense_Mutation

novel

c.824N>A

p.Gly275Glu

p.G275E

P78347

protein_coding

tolerated(0.17)

benign(0.015)

TCGA-C5-A1MP-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

GTF2I

SNV

Missense_Mutation

novel

c.88C>G

p.Leu30Val

p.L30V

P78347

protein_coding

tolerated(0.07)

probably_damaging(0.978)

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

GTF2I

SNV

Missense_Mutation

novel

c.1743G>C

p.Leu581Phe

p.L581F

P78347

protein_coding

tolerated(0.44)

possibly_damaging(0.681)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

GTF2I

SNV

Missense_Mutation

novel

c.525N>C

p.Glu175Asp

p.E175D

P78347

protein_coding

tolerated(0.11)

probably_damaging(0.996)

TCGA-VS-A8EL-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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