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: KAT2A

Gene summary for KAT2A

Gene summary.

Gene information	Species	Human
	Gene symbol	KAT2A
	Gene ID	2648
	Gene name	lysine acetyltransferase 2A
	Gene Alias	GCN5
	Cytomap	17q21.2
	Gene Type	protein-coding
	GO ID	GO:0000226
	UniProtAcc	Q92830

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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
2648	KAT2A	LZE7T	Human	Esophagus	ESCC	1.36e-07	3.03e-01	0.0667
2648	KAT2A	LZE8T	Human	Esophagus	ESCC	4.27e-02	9.18e-02	0.067
2648	KAT2A	LZE22T	Human	Esophagus	ESCC	3.22e-03	4.02e-01	0.068
2648	KAT2A	LZE24T	Human	Esophagus	ESCC	2.70e-15	4.03e-01	0.0596
2648	KAT2A	P1T-E	Human	Esophagus	ESCC	2.46e-14	7.62e-01	0.0875
2648	KAT2A	P2T-E	Human	Esophagus	ESCC	4.02e-22	3.49e-01	0.1177
2648	KAT2A	P4T-E	Human	Esophagus	ESCC	7.89e-08	2.76e-01	0.1323
2648	KAT2A	P5T-E	Human	Esophagus	ESCC	3.98e-23	2.47e-01	0.1327
2648	KAT2A	P8T-E	Human	Esophagus	ESCC	2.74e-16	2.37e-01	0.0889
2648	KAT2A	P9T-E	Human	Esophagus	ESCC	5.49e-10	2.14e-01	0.1131
2648	KAT2A	P10T-E	Human	Esophagus	ESCC	1.82e-16	2.53e-01	0.116
2648	KAT2A	P11T-E	Human	Esophagus	ESCC	3.78e-15	4.38e-01	0.1426
2648	KAT2A	P12T-E	Human	Esophagus	ESCC	5.89e-24	4.67e-01	0.1122
2648	KAT2A	P15T-E	Human	Esophagus	ESCC	2.82e-16	3.94e-01	0.1149
2648	KAT2A	P16T-E	Human	Esophagus	ESCC	5.73e-19	3.42e-01	0.1153
2648	KAT2A	P17T-E	Human	Esophagus	ESCC	1.59e-04	3.09e-01	0.1278
2648	KAT2A	P19T-E	Human	Esophagus	ESCC	3.14e-02	2.18e-01	0.1662
2648	KAT2A	P20T-E	Human	Esophagus	ESCC	5.66e-17	3.42e-01	0.1124
2648	KAT2A	P21T-E	Human	Esophagus	ESCC	2.69e-11	2.26e-01	0.1617
2648	KAT2A	P22T-E	Human	Esophagus	ESCC	1.73e-25	3.50e-01	0.1236

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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

∗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:001657015	Esophagus	ESCC	histone modification	323/8552	463/18723	2.61e-26	7.88e-24	323
GO:0031647111	Esophagus	ESCC	regulation of protein stability	223/8552	298/18723	5.76e-25	1.52e-22	223
GO:001820514	Esophagus	ESCC	peptidyl-lysine modification	259/8552	376/18723	3.90e-20	5.26e-18	259
GO:000170119	Esophagus	ESCC	in utero embryonic development	243/8552	367/18723	1.00e-15	6.86e-14	243
GO:001839413	Esophagus	ESCC	peptidyl-lysine acetylation	123/8552	169/18723	6.58e-13	2.94e-11	123
GO:004354313	Esophagus	ESCC	protein acylation	165/8552	243/18723	1.69e-12	7.14e-11	165
GO:000647313	Esophagus	ESCC	protein acetylation	140/8552	201/18723	4.37e-12	1.69e-10	140
GO:0031667111	Esophagus	ESCC	response to nutrient levels	289/8552	474/18723	9.25e-12	3.47e-10	289
GO:001839313	Esophagus	ESCC	internal peptidyl-lysine acetylation	114/8552	158/18723	1.16e-11	4.24e-10	114
GO:000647513	Esophagus	ESCC	internal protein amino acid acetylation	115/8552	160/18723	1.43e-11	5.08e-10	115
GO:00165735	Esophagus	ESCC	histone acetylation	110/8552	152/18723	1.95e-11	6.81e-10	110
GO:00457865	Esophagus	ESCC	negative regulation of cell cycle	236/8552	385/18723	3.62e-10	9.93e-09	236
GO:0010639110	Esophagus	ESCC	negative regulation of organelle organization	215/8552	348/18723	8.20e-10	2.01e-08	215
GO:003105614	Esophagus	ESCC	regulation of histone modification	106/8552	152/18723	1.52e-09	3.55e-08	106
GO:000184115	Esophagus	ESCC	neural tube formation	75/8552	102/18723	9.68e-09	1.95e-07	75
GO:000184314	Esophagus	ESCC	neural tube closure	66/8552	88/18723	1.98e-08	3.82e-07	66
GO:004396712	Esophagus	ESCC	histone H4 acetylation	53/8552	67/18723	2.11e-08	4.03e-07	53
GO:001402014	Esophagus	ESCC	primary neural tube formation	69/8552	94/18723	4.22e-08	7.76e-07	69
GO:006060614	Esophagus	ESCC	tube closure	66/8552	89/18723	4.24e-08	7.76e-07	66
GO:000632517	Esophagus	ESCC	chromatin organization	240/8552	409/18723	6.52e-08	1.14e-06	240

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05166211	Esophagus	ESCC	Human T-cell leukemia virus 1 infection	164/4205	222/8465	8.13e-14	2.09e-12	1.07e-12	164
hsa032509	Esophagus	ESCC	Viral life cycle - HIV-1	54/4205	63/8465	2.01e-09	2.17e-08	1.11e-08	54
hsa0520325	Esophagus	ESCC	Viral carcinogenesis	137/4205	204/8465	2.47e-07	1.88e-06	9.62e-07	137
hsa0491928	Esophagus	ESCC	Thyroid hormone signaling pathway	78/4205	121/8465	6.79e-04	2.23e-03	1.14e-03	78
hsa043306	Esophagus	ESCC	Notch signaling pathway	42/4205	62/8465	2.97e-03	7.97e-03	4.08e-03	42
hsa05166310	Esophagus	ESCC	Human T-cell leukemia virus 1 infection	164/4205	222/8465	8.13e-14	2.09e-12	1.07e-12	164
hsa0325014	Esophagus	ESCC	Viral life cycle - HIV-1	54/4205	63/8465	2.01e-09	2.17e-08	1.11e-08	54
hsa0520335	Esophagus	ESCC	Viral carcinogenesis	137/4205	204/8465	2.47e-07	1.88e-06	9.62e-07	137
hsa04919113	Esophagus	ESCC	Thyroid hormone signaling pathway	78/4205	121/8465	6.79e-04	2.23e-03	1.14e-03	78
hsa0433013	Esophagus	ESCC	Notch signaling pathway	42/4205	62/8465	2.97e-03	7.97e-03	4.08e-03	42
hsa0516622	Liver	HCC	Human T-cell leukemia virus 1 infection	139/4020	222/8465	3.17e-06	2.79e-05	1.55e-05	139
hsa032502	Liver	HCC	Viral life cycle - HIV-1	46/4020	63/8465	3.25e-05	1.88e-04	1.04e-04	46
hsa0491912	Liver	HCC	Thyroid hormone signaling pathway	75/4020	121/8465	8.76e-04	3.38e-03	1.88e-03	75
hsa052032	Liver	HCC	Viral carcinogenesis	117/4020	204/8465	2.68e-03	8.98e-03	5.00e-03	117
hsa0516632	Liver	HCC	Human T-cell leukemia virus 1 infection	139/4020	222/8465	3.17e-06	2.79e-05	1.55e-05	139
hsa0325011	Liver	HCC	Viral life cycle - HIV-1	46/4020	63/8465	3.25e-05	1.88e-04	1.04e-04	46
hsa0491913	Liver	HCC	Thyroid hormone signaling pathway	75/4020	121/8465	8.76e-04	3.38e-03	1.88e-03	75
hsa052033	Liver	HCC	Viral carcinogenesis	117/4020	204/8465	2.68e-03	8.98e-03	5.00e-03	117
hsa0516630	Oral cavity	OSCC	Human T-cell leukemia virus 1 infection	150/3704	222/8465	3.68e-13	7.26e-12	3.70e-12	150
hsa052038	Oral cavity	OSCC	Viral carcinogenesis	124/3704	204/8465	5.57e-07	3.28e-06	1.67e-06	124

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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
KAT2A	DC	Breast	ADJ	CMTM8,DNAJC4,ATP8B4, etc.	3.21e-02
KAT2A	CD8TEX	Breast	ADJ	CMTM8,DNAJC4,ATP8B4, etc.	4.29e-02
KAT2A	GC	Breast	ADJ	CMTM8,DNAJC4,ATP8B4, etc.	3.26e-02
KAT2A	CD8TEXP	Breast	Precancer	CMTM8,DNAJC4,ATP8B4, etc.	4.80e-02
KAT2A	INCAF	Colorectum	SER	PCNP,SLC35F2,DHX37, etc.	1.92e-01
KAT2A	LUM	Endometrium	EEC	CCNL2,WASHC1,UBA7, etc.	3.37e-02
KAT2A	CD8TEX	Endometrium	Healthy	PLEKHG2,MRM2,CENPS, etc.	1.22e-01
KAT2A	PSC	Pancreas	Healthy	NUDT12,TMEM156,RGS9, etc.	2.43e-02
KAT2A	M1MAC	Stomach	ADJ	VPS54,APOC3,CD14, etc.	1.61e-01
KAT2A	M1MAC	Stomach	CAG	VPS54,APOC3,CD14, etc.	2.23e-01

∗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

KAT2A

SNV

Missense_Mutation

c.1216N>G

p.Ile406Val

p.I406V

Q92830

protein_coding

tolerated(0.68)

benign(0)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

KAT2A

SNV

Missense_Mutation

c.2396G>A

p.Arg799Gln

p.R799Q

Q92830

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

KAT2A

SNV

Missense_Mutation

novel

c.1213N>A

p.Pro405Thr

p.P405T

Q92830

protein_coding

tolerated(0.15)

benign(0.01)

TCGA-E2-A1LS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cyclophosphamide

KAT2A

insertion

In_Frame_Ins

novel

c.2155_2156insCCCCACACCTGCTCCTGCCCTCACTGCGCCCTGCAG

p.Leu719delinsSerProHisLeuLeuLeuProSerLeuArgProAlaVal

p.L719delinsSPHLLLPSLRPAV

Q92830

protein_coding

TCGA-A2-A0T0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

KAT2A

insertion

Frame_Shift_Ins

novel

c.1664_1665insTGAGGGCCTGTGGGGCC

p.Lys555AsnfsTer46

p.K555Nfs*46

Q92830

protein_coding

TCGA-AN-A0FS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

KAT2A

SNV

Missense_Mutation

novel

c.1096N>C

p.Glu366Gln

p.E366Q

Q92830

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-C5-A2LZ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Unknown

KAT2A

SNV

Missense_Mutation

c.1442N>T

p.Ser481Leu

p.S481L

Q92830

protein_coding

deleterious(0.03)

benign(0.371)

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

KAT2A

SNV

Missense_Mutation

rs373255391

c.2299G>A

p.Glu767Lys

p.E767K

Q92830

protein_coding

deleterious(0)

benign(0.108)

TCGA-LP-A4AU-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

KAT2A

SNV

Missense_Mutation

novel

c.1018G>C

p.Glu340Gln

p.E340Q

Q92830

protein_coding

deleterious(0.01)

probably_damaging(0.969)

TCGA-MA-AA41-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

KAT2A

SNV

Missense_Mutation

novel

c.2338G>A

p.Glu780Lys

p.E780K

Q92830

protein_coding

tolerated(0.06)

probably_damaging(0.988)

TCGA-VS-A8EK-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
2648	KAT2A	TUMOR SUPPRESSOR, ENZYME		PD-146176	CHEMBL180917
2648	KAT2A	TUMOR SUPPRESSOR, ENZYME		BEXAROTENE	BEXAROTENE
2648	KAT2A	TUMOR SUPPRESSOR, ENZYME		REVERSETRIIODOTHYRONINE	REVERSETRIIODOTHYRONINE
2648	KAT2A	TUMOR SUPPRESSOR, ENZYME		OCTADEC-17-YNOIC ACID	CHEMBL182310
2648	KAT2A	TUMOR SUPPRESSOR, ENZYME		ANAZOLENE	ANAZOLENE
2648	KAT2A	TUMOR SUPPRESSOR, ENZYME		SIMAZINE	SIMAZINE
2648	KAT2A	TUMOR SUPPRESSOR, ENZYME		5,8,11,14-EICOSATETRAYNOIC ACID	CHEMBL458328
2648	KAT2A	TUMOR SUPPRESSOR, ENZYME		LINOLENIC ACID	LINOLENIC ACID
2648	KAT2A	TUMOR SUPPRESSOR, ENZYME		GAMOLENIC ACID	GAMOLENIC ACID
2648	KAT2A	TUMOR SUPPRESSOR, ENZYME		PURPURIN	PURPURIN

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