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: ACAD9

Gene summary for ACAD9

Gene summary.

Gene information	Species	Human
	Gene symbol	ACAD9
	Gene ID	28976
	Gene name	acyl-CoA dehydrogenase family member 9
	Gene Alias	MC1DN20
	Cytomap	3q21.3
	Gene Type	protein-coding
	GO ID	GO:0001676
	UniProtAcc	Q9H845

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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
28976	ACAD9	LZE2T	Human	Esophagus	ESCC	1.29e-04	5.22e-01	0.082
28976	ACAD9	LZE4T	Human	Esophagus	ESCC	1.88e-05	2.21e-01	0.0811
28976	ACAD9	LZE7T	Human	Esophagus	ESCC	1.78e-06	2.77e-01	0.0667
28976	ACAD9	LZE21D1	Human	Esophagus	HGIN	8.59e-03	3.22e-01	0.0632
28976	ACAD9	LZE22T	Human	Esophagus	ESCC	2.74e-05	4.50e-01	0.068
28976	ACAD9	LZE24T	Human	Esophagus	ESCC	1.09e-15	3.81e-01	0.0596
28976	ACAD9	P1T-E	Human	Esophagus	ESCC	2.55e-08	4.85e-01	0.0875
28976	ACAD9	P2T-E	Human	Esophagus	ESCC	2.44e-34	8.33e-01	0.1177
28976	ACAD9	P4T-E	Human	Esophagus	ESCC	1.76e-22	5.55e-01	0.1323
28976	ACAD9	P5T-E	Human	Esophagus	ESCC	4.58e-15	3.60e-01	0.1327
28976	ACAD9	P8T-E	Human	Esophagus	ESCC	2.84e-18	3.10e-01	0.0889
28976	ACAD9	P9T-E	Human	Esophagus	ESCC	1.59e-14	2.98e-01	0.1131
28976	ACAD9	P10T-E	Human	Esophagus	ESCC	7.52e-16	4.59e-01	0.116
28976	ACAD9	P11T-E	Human	Esophagus	ESCC	3.80e-10	3.88e-01	0.1426
28976	ACAD9	P12T-E	Human	Esophagus	ESCC	7.69e-24	5.73e-01	0.1122
28976	ACAD9	P15T-E	Human	Esophagus	ESCC	1.04e-31	6.50e-01	0.1149
28976	ACAD9	P16T-E	Human	Esophagus	ESCC	4.39e-26	5.49e-01	0.1153
28976	ACAD9	P17T-E	Human	Esophagus	ESCC	1.65e-08	3.04e-01	0.1278
28976	ACAD9	P19T-E	Human	Esophagus	ESCC	4.39e-08	5.83e-01	0.1662
28976	ACAD9	P20T-E	Human	Esophagus	ESCC	3.48e-19	3.87e-01	0.1124

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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:003310820	Esophagus	HGIN	mitochondrial respiratory chain complex assembly	47/2587	93/18723	3.15e-17	8.60e-15	47
GO:001025720	Esophagus	HGIN	NADH dehydrogenase complex assembly	31/2587	57/18723	5.89e-13	8.62e-11	31
GO:003298120	Esophagus	HGIN	mitochondrial respiratory chain complex I assembly	31/2587	57/18723	5.89e-13	8.62e-11	31
GO:0033108110	Esophagus	ESCC	mitochondrial respiratory chain complex assembly	83/8552	93/18723	9.56e-19	1.05e-16	83
GO:0010257110	Esophagus	ESCC	NADH dehydrogenase complex assembly	50/8552	57/18723	3.78e-11	1.24e-09	50
GO:0032981110	Esophagus	ESCC	mitochondrial respiratory chain complex I assembly	50/8552	57/18723	3.78e-11	1.24e-09	50
GO:00066318	Esophagus	ESCC	fatty acid metabolic process	217/8552	390/18723	4.21e-05	3.39e-04	217
GO:003310812	Liver	HCC	mitochondrial respiratory chain complex assembly	80/7958	93/18723	3.47e-18	4.15e-16	80
GO:000663122	Liver	HCC	fatty acid metabolic process	238/7958	390/18723	8.24e-14	4.84e-12	238
GO:001025712	Liver	HCC	NADH dehydrogenase complex assembly	50/7958	57/18723	1.50e-12	7.20e-11	50
GO:003298112	Liver	HCC	mitochondrial respiratory chain complex I assembly	50/7958	57/18723	1.50e-12	7.20e-11	50
GO:000167621	Liver	HCC	long-chain fatty acid metabolic process	60/7958	112/18723	1.17e-02	4.28e-02	60
GO:003310818	Oral cavity	OSCC	mitochondrial respiratory chain complex assembly	75/7305	93/18723	2.17e-16	1.68e-14	75
GO:001025718	Oral cavity	OSCC	NADH dehydrogenase complex assembly	45/7305	57/18723	8.53e-10	2.13e-08	45
GO:003298118	Oral cavity	OSCC	mitochondrial respiratory chain complex I assembly	45/7305	57/18723	8.53e-10	2.13e-08	45
GO:00066317	Oral cavity	OSCC	fatty acid metabolic process	186/7305	390/18723	2.65e-04	1.69e-03	186
GO:003310819	Oral cavity	LP	mitochondrial respiratory chain complex assembly	63/4623	93/18723	2.24e-18	4.13e-16	63
GO:001025719	Oral cavity	LP	NADH dehydrogenase complex assembly	41/4623	57/18723	7.93e-14	7.89e-12	41
GO:003298119	Oral cavity	LP	mitochondrial respiratory chain complex I assembly	41/4623	57/18723	7.93e-14	7.89e-12	41
GO:003310824	Skin	cSCC	mitochondrial respiratory chain complex assembly	64/4864	93/18723	5.48e-18	6.58e-16	64

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

ACAD9

SNV

Missense_Mutation

novel

c.1537N>C

p.Glu513Gln

p.E513Q

Q9H845

protein_coding

deleterious(0.01)

benign(0.139)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

ACAD9

SNV

Missense_Mutation

c.1775N>G

p.Glu592Gly

p.E592G

Q9H845

protein_coding

tolerated(0.18)

benign(0.003)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ACAD9

SNV

Missense_Mutation

c.1771N>G

p.Pro591Ala

p.P591A

Q9H845

protein_coding

tolerated(0.51)

benign(0.012)

TCGA-BH-A0BA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

ACAD9

SNV

Missense_Mutation

c.1048N>A

p.Ala350Thr

p.A350T

Q9H845

protein_coding

tolerated(0.16)

possibly_damaging(0.495)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

ACAD9

insertion

In_Frame_Ins

novel

c.661_662insCCAACACCATGTACTCAAGACTAGGGGAGATCATCAGCATGG

p.Asn221delinsThrAsnThrMetTyrSerArgLeuGlyGluIleIleSerMetAsp

p.N221delinsTNTMYSRLGEIISMD

Q9H845

protein_coding

TCGA-A8-A07G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

5-fluorouracil

ACAD9

SNV

Missense_Mutation

rs781520431

c.1336N>T

p.Arg446Cys

p.R446C

Q9H845

protein_coding

deleterious(0)

benign(0.003)

TCGA-VS-A9U6-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ACAD9

SNV

Missense_Mutation

c.362N>T

p.Ser121Phe

p.S121F

Q9H845

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-AA-3710-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

ACAD9

SNV

Missense_Mutation

rs748758547

c.231C>A

p.Phe77Leu

p.F77L

Q9H845

protein_coding

deleterious(0.03)

probably_damaging(0.978)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

ACAD9

SNV

Missense_Mutation

rs201248046

c.1009N>G

p.Ser337Gly

p.S337G

Q9H845

protein_coding

tolerated(0.14)

benign(0.039)

TCGA-AA-A02R-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

ACAD9

SNV

Missense_Mutation

novel

c.758N>A

p.Gly253Glu

p.G253E

Q9H845

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AM-5820-01

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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