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: KIT

Gene summary for KIT

Gene summary.

Gene information	Species	Human
	Gene symbol	KIT
	Gene ID	3815
	Gene name	KIT proto-oncogene, receptor tyrosine kinase
	Gene Alias	C-Kit
	Cytomap	4q12
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	A0A024RDA0

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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
3815	KIT	CA_HPV_1	Human	Cervix	CC	8.43e-19	-5.22e-01	0.0264
3815	KIT	HSIL_HPV_2	Human	Cervix	HSIL_HPV	2.69e-05	4.16e-03	0.0208
3815	KIT	N_HPV_2	Human	Cervix	N_HPV	1.74e-04	-4.11e-01	-0.0131
3815	KIT	CCI_1	Human	Cervix	CC	3.82e-02	-6.26e-01	0.528
3815	KIT	CCI_2	Human	Cervix	CC	1.64e-03	-6.47e-01	0.5249
3815	KIT	CCI_3	Human	Cervix	CC	6.60e-06	-6.47e-01	0.516
3815	KIT	CCII_1	Human	Cervix	CC	7.51e-09	-6.47e-01	0.3249
3815	KIT	Tumor	Human	Cervix	CC	2.56e-26	-6.47e-01	0.1241
3815	KIT	sample1	Human	Cervix	CC	4.04e-07	-6.47e-01	0.0959
3815	KIT	sample3	Human	Cervix	CC	2.05e-24	-6.47e-01	0.1387
3815	KIT	H2	Human	Cervix	HSIL_HPV	4.26e-21	-6.30e-01	0.0632
3815	KIT	L1	Human	Cervix	CC	7.11e-10	-6.47e-01	0.0802
3815	KIT	T1	Human	Cervix	CC	3.62e-15	-6.42e-01	0.0918
3815	KIT	T3	Human	Cervix	CC	1.16e-23	-6.47e-01	0.1389
3815	KIT	C46	Human	Oral cavity	OSCC	4.79e-03	5.01e-02	0.1673
3815	KIT	LN46	Human	Oral cavity	OSCC	2.27e-04	1.34e-01	0.1666
3815	KIT	EOLP-1	Human	Oral cavity	EOLP	1.56e-14	6.63e-01	-0.0202
3815	KIT	EOLP-2	Human	Oral cavity	EOLP	2.93e-21	8.39e-01	-0.0203
3815	KIT	NEOLP-1	Human	Oral cavity	NEOLP	6.26e-04	4.10e-01	-0.0194

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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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma

∗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:004668616	Oral cavity	OSCC	response to cadmium ion	46/7305	68/18723	1.61e-06	2.11e-05	46
GO:00467779	Oral cavity	OSCC	protein autophosphorylation	123/7305	227/18723	2.31e-06	2.93e-05	123
GO:000836016	Oral cavity	OSCC	regulation of cell shape	88/7305	154/18723	3.73e-06	4.42e-05	88
GO:004586016	Oral cavity	OSCC	positive regulation of protein kinase activity	194/7305	386/18723	3.90e-06	4.59e-05	194
GO:00066432	Oral cavity	OSCC	membrane lipid metabolic process	111/7305	203/18723	4.02e-06	4.69e-05	111
GO:003153216	Oral cavity	OSCC	actin cytoskeleton reorganization	65/7305	107/18723	4.25e-06	4.93e-05	65
GO:001003820	Oral cavity	OSCC	response to metal ion	188/7305	373/18723	4.34e-06	5.00e-05	188
GO:003367418	Oral cavity	OSCC	positive regulation of kinase activity	228/7305	467/18723	8.31e-06	8.90e-05	228
GO:19031316	Oral cavity	OSCC	mononuclear cell differentiation	210/7305	426/18723	8.44e-06	9.02e-05	210
GO:00507696	Oral cavity	OSCC	positive regulation of neurogenesis	120/7305	225/18723	8.45e-06	9.02e-05	120
GO:000961210	Oral cavity	OSCC	response to mechanical stimulus	115/7305	216/18723	1.43e-05	1.44e-04	115
GO:003134610	Oral cavity	OSCC	positive regulation of cell projection organization	176/7305	353/18723	1.94e-05	1.87e-04	176
GO:00719028	Oral cavity	OSCC	positive regulation of protein serine/threonine kinase activity	107/7305	200/18723	2.12e-05	2.02e-04	107
GO:00510917	Oral cavity	OSCC	positive regulation of DNA-binding transcription factor activity	134/7305	260/18723	2.52e-05	2.35e-04	134
GO:005067310	Oral cavity	OSCC	epithelial cell proliferation	212/7305	437/18723	2.82e-05	2.61e-04	212
GO:000166719	Oral cavity	OSCC	ameboidal-type cell migration	228/7305	475/18723	3.46e-05	3.10e-04	228
GO:009758110	Oral cavity	OSCC	lamellipodium organization	54/7305	90/18723	4.39e-05	3.76e-04	54
GO:00507679	Oral cavity	OSCC	regulation of neurogenesis	179/7305	364/18723	4.49e-05	3.84e-04	179
GO:006049110	Oral cavity	OSCC	regulation of cell projection assembly	100/7305	188/18723	5.27e-05	4.38e-04	100
GO:00094164	Oral cavity	OSCC	response to light stimulus	159/7305	320/18723	5.98e-05	4.92e-04	159

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0401512	Cervix	CC	Rap1 signaling pathway	56/1267	210/8465	6.23e-06	5.61e-05	3.32e-05	56
hsa040142	Cervix	CC	Ras signaling pathway	51/1267	236/8465	3.55e-03	1.34e-02	7.91e-03	51
hsa040109	Cervix	CC	MAPK signaling pathway	62/1267	302/8465	4.89e-03	1.67e-02	9.86e-03	62
hsa0523010	Cervix	CC	Central carbon metabolism in cancer	18/1267	70/8465	1.29e-02	3.87e-02	2.29e-02	18
hsa05224	Cervix	CC	Breast cancer	32/1267	147/8465	1.66e-02	4.88e-02	2.88e-02	32
hsa0401513	Cervix	CC	Rap1 signaling pathway	56/1267	210/8465	6.23e-06	5.61e-05	3.32e-05	56
hsa0401411	Cervix	CC	Ras signaling pathway	51/1267	236/8465	3.55e-03	1.34e-02	7.91e-03	51
hsa0401012	Cervix	CC	MAPK signaling pathway	62/1267	302/8465	4.89e-03	1.67e-02	9.86e-03	62
hsa0523013	Cervix	CC	Central carbon metabolism in cancer	18/1267	70/8465	1.29e-02	3.87e-02	2.29e-02	18
hsa052241	Cervix	CC	Breast cancer	32/1267	147/8465	1.66e-02	4.88e-02	2.88e-02	32
hsa04640	Cervix	HSIL_HPV	Hematopoietic cell lineage	18/459	99/8465	4.97e-06	8.10e-05	6.54e-05	18
hsa046401	Cervix	HSIL_HPV	Hematopoietic cell lineage	18/459	99/8465	4.97e-06	8.10e-05	6.54e-05	18
hsa041516	Oral cavity	OSCC	PI3K-Akt signaling pathway	185/3704	354/8465	6.26e-04	1.86e-03	9.49e-04	185
hsa0415113	Oral cavity	OSCC	PI3K-Akt signaling pathway	185/3704	354/8465	6.26e-04	1.86e-03	9.49e-04	185
hsa0401023	Oral cavity	EOLP	MAPK signaling pathway	68/1218	302/8465	7.48e-05	3.40e-04	2.01e-04	68
hsa0415123	Oral cavity	EOLP	PI3K-Akt signaling pathway	73/1218	354/8465	7.03e-04	2.69e-03	1.59e-03	73
hsa0522121	Oral cavity	EOLP	Acute myeloid leukemia	19/1218	67/8465	2.20e-03	7.32e-03	4.32e-03	19
hsa040722	Oral cavity	EOLP	Phospholipase D signaling pathway	31/1218	148/8465	1.82e-02	4.67e-02	2.76e-02	31
hsa0523041	Oral cavity	EOLP	Central carbon metabolism in cancer	17/1218	70/8465	1.87e-02	4.75e-02	2.80e-02	17
hsa0401033	Oral cavity	EOLP	MAPK signaling pathway	68/1218	302/8465	7.48e-05	3.40e-04	2.01e-04	68

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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
KITLG	KIT	KITL_KIT	KIT	Breast	Healthy
KITLG	KIT	KITL_KIT	KIT	Cervix	CC
KITLG	KIT	KITL_KIT	KIT	Cervix	Healthy
KITLG	KIT	KITL_KIT	KIT	Cervix	Precancer
KITLG	KIT	KITL_KIT	KIT	CRC	Healthy
KITLG	KIT	KITL_KIT	KIT	Endometrium	AEH
KITLG	KIT	KITL_KIT	KIT	Endometrium	EEC
KITLG	KIT	KITL_KIT	KIT	Esophagus	ESCC
KITLG	KIT	KITL_KIT	KIT	HNSCC	OSCC
KITLG	KIT	KITL_KIT	KIT	HNSCC	Precancer
KITLG	KIT	KITL_KIT	KIT	Lung	AAH
KITLG	KIT	KITL_KIT	KIT	Lung	AIS
KITLG	KIT	KITL_KIT	KIT	Lung	IAC
KITLG	KIT	KITL_KIT	KIT	Lung	MIAC
KITLG	KIT	KITL_KIT	KIT	Lung	Precancer
KITLG	KIT	KITL_KIT	KIT	Skin	ADJ
KITLG	KIT	KITL_KIT	KIT	Skin	AK
KITLG	KIT	KITL_KIT	KIT	Skin	cSCC

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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

KIT

SNV

Missense_Mutation

c.656C>T

p.Ala219Val

p.A219V

P10721

protein_coding

tolerated(0.25)

benign(0.019)

TCGA-A8-A07G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

5-fluorouracil

KIT

SNV

Missense_Mutation

c.117N>G

p.Ile39Met

p.I39M

P10721

protein_coding

deleterious(0)

probably_damaging(0.989)

TCGA-A8-A095-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

KIT

SNV

Missense_Mutation

c.1295G>A

p.Gly432Glu

p.G432E

P10721

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A8-A09A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

KIT

SNV

Missense_Mutation

rs753318751

c.771G>T

p.Glu257Asp

p.E257D

P10721

protein_coding

tolerated(0.62)

benign(0.011)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

KIT

SNV

Missense_Mutation

rs386833402

c.839N>T

p.Ala280Val

p.A280V

P10721

protein_coding

tolerated(1)

benign(0.001)

TCGA-AN-A04A-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

KIT

SNV

Missense_Mutation

rs143772138

c.2057N>A

p.Arg686His

p.R686H

P10721

protein_coding

deleterious(0.01)

benign(0.096)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

KIT

SNV

Missense_Mutation

novel

c.1391N>T

p.Ser464Leu

p.S464L

P10721

protein_coding

tolerated(0.35)

benign(0.172)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

KIT

SNV

Missense_Mutation

rs781633384

c.106C>A

p.Pro36Thr

p.P36T

P10721

protein_coding

tolerated(0.39)

benign(0.112)

TCGA-C8-A1HM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

KIT

insertion

Nonsense_Mutation

novel

c.2253_2254insCAAGGAGACCTCAGTAAATATTATTGATGG

p.Asp751_Val752insGlnGlyAspLeuSerLysTyrTyrTerTrp

p.D751_V752insQGDLSKYY*W

P10721

protein_coding

TCGA-AN-A049-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

KIT

SNV

Missense_Mutation

novel

c.2401A>G

p.Thr801Ala

p.T801A

P10721

protein_coding

deleterious(0)

probably_damaging(0.982)

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
3815	KIT	CLINICALLY ACTIONABLE, KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TYROSINE KINASE, DRUG RESISTANCE, EXTERNAL SIDE OF PLASMA MEMBRANE		Pazopanib HCl
3815	KIT	CLINICALLY ACTIONABLE, KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TYROSINE KINASE, DRUG RESISTANCE, EXTERNAL SIDE OF PLASMA MEMBRANE	inhibitor	178102337	SORAFENIB
3815	KIT	CLINICALLY ACTIONABLE, KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TYROSINE KINASE, DRUG RESISTANCE, EXTERNAL SIDE OF PLASMA MEMBRANE		G007-LK		28611108
3815	KIT	CLINICALLY ACTIONABLE, KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TYROSINE KINASE, DRUG RESISTANCE, EXTERNAL SIDE OF PLASMA MEMBRANE		Sorafenib	SORAFENIB
3815	KIT	CLINICALLY ACTIONABLE, KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TYROSINE KINASE, DRUG RESISTANCE, EXTERNAL SIDE OF PLASMA MEMBRANE	inhibitor	4'-N-BENZOYLSTAUROSPORINE
3815	KIT	CLINICALLY ACTIONABLE, KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TYROSINE KINASE, DRUG RESISTANCE, EXTERNAL SIDE OF PLASMA MEMBRANE	inhibitor	CHEMBL124660	TANDUTINIB
3815	KIT	CLINICALLY ACTIONABLE, KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TYROSINE KINASE, DRUG RESISTANCE, EXTERNAL SIDE OF PLASMA MEMBRANE	inhibitor	178102585	DOVITINIB
3815	KIT	CLINICALLY ACTIONABLE, KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TYROSINE KINASE, DRUG RESISTANCE, EXTERNAL SIDE OF PLASMA MEMBRANE	inhibitor	178102286	QUIZARTINIB
3815	KIT	CLINICALLY ACTIONABLE, KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TYROSINE KINASE, DRUG RESISTANCE, EXTERNAL SIDE OF PLASMA MEMBRANE	inhibitor	328083485	OSI-930
3815	KIT	CLINICALLY ACTIONABLE, KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TYROSINE KINASE, DRUG RESISTANCE, EXTERNAL SIDE OF PLASMA MEMBRANE		OSI-930	OSI-930

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