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: IDH3A

Gene summary for IDH3A

Gene summary.

Gene information	Species	Human
	Gene symbol	IDH3A
	Gene ID	3419
	Gene name	isocitrate dehydrogenase (NAD(+)) 3 catalytic subunit alpha
	Gene Alias	RP90
	Cytomap	15q25.1
	Gene Type	protein-coding
	GO ID	GO:0005975
	UniProtAcc	P50213

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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
3419	IDH3A	LZE4T	Human	Esophagus	ESCC	1.10e-11	4.70e-01	0.0811
3419	IDH3A	LZE7T	Human	Esophagus	ESCC	1.14e-04	3.39e-01	0.0667
3419	IDH3A	LZE8T	Human	Esophagus	ESCC	1.64e-08	2.83e-01	0.067
3419	IDH3A	LZE20T	Human	Esophagus	ESCC	3.79e-02	1.59e-01	0.0662
3419	IDH3A	LZE24T	Human	Esophagus	ESCC	4.30e-08	2.87e-01	0.0596
3419	IDH3A	LZE21T	Human	Esophagus	ESCC	3.18e-03	2.65e-01	0.0655
3419	IDH3A	LZE6T	Human	Esophagus	ESCC	3.73e-05	1.59e-01	0.0845
3419	IDH3A	P2T-E	Human	Esophagus	ESCC	1.19e-20	2.98e-01	0.1177
3419	IDH3A	P4T-E	Human	Esophagus	ESCC	1.38e-16	5.87e-01	0.1323
3419	IDH3A	P5T-E	Human	Esophagus	ESCC	2.07e-12	1.66e-01	0.1327
3419	IDH3A	P8T-E	Human	Esophagus	ESCC	1.69e-12	2.73e-01	0.0889
3419	IDH3A	P9T-E	Human	Esophagus	ESCC	1.67e-22	6.90e-01	0.1131
3419	IDH3A	P10T-E	Human	Esophagus	ESCC	1.71e-23	4.30e-01	0.116
3419	IDH3A	P11T-E	Human	Esophagus	ESCC	1.36e-13	5.51e-01	0.1426
3419	IDH3A	P12T-E	Human	Esophagus	ESCC	2.46e-29	6.82e-01	0.1122
3419	IDH3A	P15T-E	Human	Esophagus	ESCC	1.37e-24	5.80e-01	0.1149
3419	IDH3A	P16T-E	Human	Esophagus	ESCC	1.60e-22	4.38e-01	0.1153
3419	IDH3A	P19T-E	Human	Esophagus	ESCC	1.15e-07	8.97e-01	0.1662
3419	IDH3A	P20T-E	Human	Esophagus	ESCC	3.23e-26	4.81e-01	0.1124
3419	IDH3A	P21T-E	Human	Esophagus	ESCC	1.80e-34	8.04e-01	0.1617

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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:0006091110	Esophagus	ESCC	generation of precursor metabolites and energy	331/8552	490/18723	3.86e-23	8.45e-21	331
GO:0045333110	Esophagus	ESCC	cellular respiration	173/8552	230/18723	4.53e-20	5.99e-18	173
GO:0009060110	Esophagus	ESCC	aerobic respiration	145/8552	189/18723	2.16e-18	2.21e-16	145
GO:0015980110	Esophagus	ESCC	energy derivation by oxidation of organic compounds	220/8552	318/18723	1.20e-17	1.09e-15	220
GO:00060997	Esophagus	ESCC	tricarboxylic acid cycle	27/8552	30/18723	4.54e-07	6.15e-06	27
GO:00060668	Esophagus	ESCC	alcohol metabolic process	202/8552	353/18723	7.32e-06	7.26e-05	202
GO:19026524	Esophagus	ESCC	secondary alcohol metabolic process	87/8552	147/18723	6.58e-04	3.50e-03	87
GO:00723503	Esophagus	ESCC	tricarboxylic acid metabolic process	12/8552	14/18723	2.51e-03	1.08e-02	12
GO:000609122	Liver	HCC	generation of precursor metabolites and energy	340/7958	490/18723	4.04e-34	2.85e-31	340
GO:000906012	Liver	HCC	aerobic respiration	147/7958	189/18723	3.13e-23	6.61e-21	147
GO:004533312	Liver	HCC	cellular respiration	171/7958	230/18723	6.35e-23	1.26e-20	171
GO:001598022	Liver	HCC	energy derivation by oxidation of organic compounds	221/7958	318/18723	1.02e-22	1.86e-20	221
GO:000606621	Liver	HCC	alcohol metabolic process	208/7958	353/18723	2.80e-10	9.50e-09	208
GO:19026522	Liver	HCC	secondary alcohol metabolic process	100/7958	147/18723	3.26e-10	1.09e-08	100
GO:000609911	Liver	HCC	tricarboxylic acid cycle	27/7958	30/18723	7.59e-08	1.52e-06	27
GO:00723501	Liver	HCC	tricarboxylic acid metabolic process	11/7958	14/18723	6.81e-03	2.73e-02	11
GO:000609118	Oral cavity	OSCC	generation of precursor metabolites and energy	286/7305	490/18723	1.45e-18	1.71e-16	286
GO:000906018	Oral cavity	OSCC	aerobic respiration	133/7305	189/18723	1.79e-18	2.02e-16	133
GO:004533318	Oral cavity	OSCC	cellular respiration	153/7305	230/18723	2.07e-17	1.87e-15	153
GO:001598018	Oral cavity	OSCC	energy derivation by oxidation of organic compounds	190/7305	318/18723	4.10e-14	2.26e-12	190

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0002014	Esophagus	ESCC	Citrate cycle (TCA cycle)	27/4205	30/8465	3.48e-06	1.94e-05	9.95e-06	27
hsa0120023	Esophagus	ESCC	Carbon metabolism	79/4205	115/8465	2.50e-05	1.21e-04	6.22e-05	79
hsa0123023	Esophagus	ESCC	Biosynthesis of amino acids	49/4205	75/8465	4.35e-03	1.12e-02	5.74e-03	49
hsa0002015	Esophagus	ESCC	Citrate cycle (TCA cycle)	27/4205	30/8465	3.48e-06	1.94e-05	9.95e-06	27
hsa0120033	Esophagus	ESCC	Carbon metabolism	79/4205	115/8465	2.50e-05	1.21e-04	6.22e-05	79
hsa0123033	Esophagus	ESCC	Biosynthesis of amino acids	49/4205	75/8465	4.35e-03	1.12e-02	5.74e-03	49
hsa0120041	Liver	HCC	Carbon metabolism	89/4020	115/8465	3.92e-11	6.56e-10	3.65e-10	89
hsa0002021	Liver	HCC	Citrate cycle (TCA cycle)	28/4020	30/8465	1.08e-07	1.44e-06	8.02e-07	28
hsa0123021	Liver	HCC	Biosynthesis of amino acids	53/4020	75/8465	3.79e-05	2.11e-04	1.18e-04	53
hsa0120051	Liver	HCC	Carbon metabolism	89/4020	115/8465	3.92e-11	6.56e-10	3.65e-10	89
hsa0002031	Liver	HCC	Citrate cycle (TCA cycle)	28/4020	30/8465	1.08e-07	1.44e-06	8.02e-07	28
hsa0123031	Liver	HCC	Biosynthesis of amino acids	53/4020	75/8465	3.79e-05	2.11e-04	1.18e-04	53
hsa0002012	Oral cavity	OSCC	Citrate cycle (TCA cycle)	26/3704	30/8465	1.38e-06	7.46e-06	3.80e-06	26
hsa0120014	Oral cavity	OSCC	Carbon metabolism	74/3704	115/8465	6.10e-06	3.05e-05	1.55e-05	74
hsa012305	Oral cavity	OSCC	Biosynthesis of amino acids	45/3704	75/8465	3.27e-03	8.23e-03	4.19e-03	45
hsa0002013	Oral cavity	OSCC	Citrate cycle (TCA cycle)	26/3704	30/8465	1.38e-06	7.46e-06	3.80e-06	26
hsa0120015	Oral cavity	OSCC	Carbon metabolism	74/3704	115/8465	6.10e-06	3.05e-05	1.55e-05	74
hsa0123012	Oral cavity	OSCC	Biosynthesis of amino acids	45/3704	75/8465	3.27e-03	8.23e-03	4.19e-03	45
hsa0120022	Oral cavity	LP	Carbon metabolism	62/2418	115/8465	8.38e-09	1.39e-07	8.99e-08	62
hsa0002022	Oral cavity	LP	Citrate cycle (TCA cycle)	22/2418	30/8465	4.66e-07	5.97e-06	3.85e-06	22

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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

IDH3A

SNV

Missense_Mutation

novel

c.1019N>T

p.Ser340Ile

p.S340I

P50213

protein_coding

tolerated(0.39)

benign(0.003)

TCGA-AC-A3W5-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

IDH3A

SNV

Missense_Mutation

c.263N>C

p.Met88Thr

p.M88T

P50213

protein_coding

deleterious(0)

benign(0.281)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

IDH3A

SNV

Missense_Mutation

c.316N>A

p.Gly106Ser

p.G106S

P50213

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-E2-A1B0-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

IDH3A

insertion

Nonsense_Mutation

novel

c.1095_1096insTAAGAGTTAATGATTTAGGCAGGTGTGGTGGTGCATGCCT

p.Asp366Ter

p.D366*

P50213

protein_coding

TCGA-A8-A07J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

IDH3A

insertion

Nonsense_Mutation

novel

c.338_339insCCCGTGAGGAAGTGTTCCTCCTTCATTTGAATCTCAGGTAGA

p.Leu113_Leu114insProTerGlySerValProProSerPheGluSerGlnValGlu

p.L113_L114insP*GSVPPSFESQVE

P50213

protein_coding

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

IDH3A

insertion

Frame_Shift_Ins

novel

c.247_248insCCAAAGTTGAAAAAGGGCTGGGCCCGGTAGCTCACGTCTGTAATCCC

p.Glu83AlafsTer29

p.E83Afs*29

P50213

protein_coding

TCGA-AO-A0J5-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate

zoledronic

IDH3A

insertion

Frame_Shift_Ins

novel

c.423_424insGG

p.Ile142GlyfsTer3

p.I142Gfs*3

P50213

protein_coding

TCGA-BH-A0AY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

IDH3A

insertion

Frame_Shift_Ins

novel

c.424_425insCTACAGGTGTGCCACCATGCCCAACTAATTTTTTAAAAAGTTTT

p.Ile142ThrfsTer17

p.I142Tfs*17

P50213

protein_coding

TCGA-BH-A0AY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

IDH3A

SNV

Missense_Mutation

c.553N>C

p.Glu185Gln

p.E185Q

P50213

protein_coding

tolerated(0.32)

benign(0.079)

TCGA-DG-A2KL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

IDH3A

SNV

Missense_Mutation

rs747375549

c.415G>A

p.Asp139Asn

p.D139N

P50213

protein_coding

tolerated(1)

benign(0.014)

TCGA-HM-A4S6-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

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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