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: AACS

Gene summary for AACS

Gene summary.

Gene information	Species	Human
	Gene symbol	AACS
	Gene ID	65985
	Gene name	acetoacetyl-CoA synthetase
	Gene Alias	ACSF1
	Cytomap	12q24.31
	Gene Type	protein-coding
	GO ID	GO:0001678
	UniProtAcc	Q86V21

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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
65985	AACS	LZE24T	Human	Esophagus	ESCC	1.53e-08	3.01e-01	0.0596
65985	AACS	P1T-E	Human	Esophagus	ESCC	7.87e-05	1.69e-01	0.0875
65985	AACS	P2T-E	Human	Esophagus	ESCC	1.13e-21	3.35e-01	0.1177
65985	AACS	P4T-E	Human	Esophagus	ESCC	8.55e-13	3.91e-01	0.1323
65985	AACS	P5T-E	Human	Esophagus	ESCC	8.85e-15	2.44e-01	0.1327
65985	AACS	P8T-E	Human	Esophagus	ESCC	9.81e-13	2.38e-01	0.0889
65985	AACS	P9T-E	Human	Esophagus	ESCC	3.45e-07	5.87e-02	0.1131
65985	AACS	P10T-E	Human	Esophagus	ESCC	3.16e-15	2.11e-01	0.116
65985	AACS	P11T-E	Human	Esophagus	ESCC	6.14e-06	2.59e-01	0.1426
65985	AACS	P12T-E	Human	Esophagus	ESCC	1.75e-15	2.45e-01	0.1122
65985	AACS	P15T-E	Human	Esophagus	ESCC	1.70e-16	2.15e-01	0.1149
65985	AACS	P16T-E	Human	Esophagus	ESCC	4.77e-07	2.02e-01	0.1153
65985	AACS	P17T-E	Human	Esophagus	ESCC	3.30e-04	1.94e-01	0.1278
65985	AACS	P19T-E	Human	Esophagus	ESCC	2.44e-02	6.31e-01	0.1662
65985	AACS	P20T-E	Human	Esophagus	ESCC	5.69e-21	4.03e-01	0.1124
65985	AACS	P21T-E	Human	Esophagus	ESCC	6.04e-14	2.79e-01	0.1617
65985	AACS	P22T-E	Human	Esophagus	ESCC	3.13e-06	1.20e-01	0.1236
65985	AACS	P23T-E	Human	Esophagus	ESCC	9.20e-12	3.89e-01	0.108
65985	AACS	P24T-E	Human	Esophagus	ESCC	4.05e-09	1.58e-01	0.1287
65985	AACS	P26T-E	Human	Esophagus	ESCC	2.02e-09	1.13e-01	0.1276

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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
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:0006091110	Esophagus	ESCC	generation of precursor metabolites and energy	331/8552	490/18723	3.86e-23	8.45e-21	331
GO:1904951111	Esophagus	ESCC	positive regulation of establishment of protein localization	216/8552	319/18723	1.01e-15	6.86e-14	216
GO:0051222111	Esophagus	ESCC	positive regulation of protein transport	204/8552	303/18723	1.56e-14	8.38e-13	204
GO:0048732111	Esophagus	ESCC	gland development	269/8552	436/18723	7.81e-12	2.95e-10	269
GO:0031667111	Esophagus	ESCC	response to nutrient levels	289/8552	474/18723	9.25e-12	3.47e-10	289
GO:004259419	Esophagus	ESCC	response to starvation	133/8552	197/18723	4.31e-10	1.14e-08	133
GO:000758410	Esophagus	ESCC	response to nutrient	114/8552	174/18723	9.43e-08	1.56e-06	114
GO:0061008110	Esophagus	ESCC	hepaticobiliary system development	98/8552	150/18723	8.91e-07	1.15e-05	98
GO:0001889110	Esophagus	ESCC	liver development	96/8552	147/18723	1.18e-06	1.47e-05	96
GO:1901654111	Esophagus	ESCC	response to ketone	118/8552	194/18723	1.45e-05	1.31e-04	118
GO:00454449	Esophagus	ESCC	fat cell differentiation	135/8552	229/18723	3.38e-05	2.78e-04	135
GO:00066318	Esophagus	ESCC	fatty acid metabolic process	217/8552	390/18723	4.21e-05	3.39e-04	217
GO:000941020	Esophagus	ESCC	response to xenobiotic stimulus	253/8552	462/18723	4.55e-05	3.58e-04	253
GO:19016556	Esophagus	ESCC	cellular response to ketone	59/8552	96/18723	1.32e-03	6.30e-03	59
GO:003357415	Esophagus	ESCC	response to testosterone	29/8552	42/18723	1.87e-03	8.46e-03	29
GO:0097305111	Esophagus	ESCC	response to alcohol	138/8552	253/18723	2.70e-03	1.14e-02	138
GO:000930617	Esophagus	ESCC	protein secretion	190/8552	359/18723	3.22e-03	1.34e-02	190
GO:003559217	Esophagus	ESCC	establishment of protein localization to extracellular region	190/8552	360/18723	3.77e-03	1.53e-02	190
GO:007169210	Esophagus	ESCC	protein localization to extracellular region	193/8552	368/18723	5.01e-03	1.92e-02	193
GO:0009743111	Esophagus	ESCC	response to carbohydrate	135/8552	253/18723	8.16e-03	2.89e-02	135

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa002809	Esophagus	ESCC	Valine, leucine and isoleucine degradation	34/4205	48/8465	2.34e-03	6.54e-03	3.35e-03	34
hsa0028014	Esophagus	ESCC	Valine, leucine and isoleucine degradation	34/4205	48/8465	2.34e-03	6.54e-03	3.35e-03	34
hsa0028021	Liver	Cirrhotic	Valine, leucine and isoleucine degradation	32/2530	48/8465	1.45e-07	2.02e-06	1.24e-06	32
hsa006502	Liver	Cirrhotic	Butanoate metabolism	15/2530	27/8465	4.71e-03	1.74e-02	1.07e-02	15
hsa0028031	Liver	Cirrhotic	Valine, leucine and isoleucine degradation	32/2530	48/8465	1.45e-07	2.02e-06	1.24e-06	32
hsa006503	Liver	Cirrhotic	Butanoate metabolism	15/2530	27/8465	4.71e-03	1.74e-02	1.07e-02	15
hsa0028041	Liver	HCC	Valine, leucine and isoleucine degradation	41/4020	48/8465	4.84e-08	7.05e-07	3.92e-07	41
hsa0028051	Liver	HCC	Valine, leucine and isoleucine degradation	41/4020	48/8465	4.84e-08	7.05e-07	3.92e-07	41

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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

AACS

SNV

Missense_Mutation

rs764827940

c.592C>G

p.Gln198Glu

p.Q198E

Q86V21

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

AACS

SNV

Missense_Mutation

c.324N>G

p.His108Gln

p.H108Q

Q86V21

protein_coding

deleterious(0.03)

possibly_damaging(0.582)

TCGA-AO-A0J5-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate

zoledronic

AACS

SNV

Missense_Mutation

novel

c.1025T>G

p.Val342Gly

p.V342G

Q86V21

protein_coding

deleterious(0.01)

probably_damaging(0.966)

TCGA-C8-A273-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

AACS

insertion

Frame_Shift_Ins

novel

c.748_749insCTGGAGTGCAATGGCACGA

p.Leu250ProfsTer18

p.L250Pfs*18

Q86V21

protein_coding

TCGA-BH-A0E7-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

AACS

SNV

Missense_Mutation

novel

c.464N>A

p.Arg155Gln

p.R155Q

Q86V21

protein_coding

deleterious(0)

probably_damaging(0.98)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

AACS

SNV

Missense_Mutation

c.1070C>G

p.Ser357Cys

p.S357C

Q86V21

protein_coding

deleterious(0)

possibly_damaging(0.774)

TCGA-C5-A3HE-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

AACS

SNV

Missense_Mutation

rs552206706

c.1384C>T

p.Arg462Trp

p.R462W

Q86V21

protein_coding

deleterious(0)

benign(0.234)

TCGA-VS-A94Z-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

AACS

SNV

Missense_Mutation

novel

c.515N>G

p.Ala172Gly

p.A172G

Q86V21

protein_coding

deleterious(0.02)

benign(0.255)

TCGA-VS-A9UC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

AACS

SNV

Missense_Mutation

c.192N>T

p.Glu64Asp

p.E64D

Q86V21

protein_coding

tolerated(0.26)

benign(0.046)

TCGA-AA-3977-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

AACS

SNV

Missense_Mutation

novel

c.179N>G

p.Asp60Gly

p.D60G

Q86V21

protein_coding

tolerated(0.1)

possibly_damaging(0.816)

TCGA-AA-3984-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

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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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