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: COX10

Gene summary for COX10

Gene summary.

Gene information	Species	Human
	Gene symbol	COX10
	Gene ID	1352
	Gene name	cytochrome c oxidase assembly factor heme A:farnesyltransferase COX10
	Gene Alias	MC4DN3
	Cytomap	17p12
	Gene Type	protein-coding
	GO ID	GO:0000266
	UniProtAcc	Q12887

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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
1352	COX10	HTA11_3410_2000001011	Human	Colorectum	AD	9.51e-11	-5.44e-01	0.0155
1352	COX10	HTA11_2487_2000001011	Human	Colorectum	SER	2.35e-03	-4.87e-01	-0.1808
1352	COX10	HTA11_696_2000001011	Human	Colorectum	AD	2.04e-06	-3.66e-01	-0.1464
1352	COX10	HTA11_866_2000001011	Human	Colorectum	AD	3.22e-06	-3.70e-01	-0.1001
1352	COX10	HTA11_10711_2000001011	Human	Colorectum	AD	1.01e-03	-5.23e-01	0.0338
1352	COX10	HTA11_7696_3000711011	Human	Colorectum	AD	3.40e-05	-3.49e-01	0.0674
1352	COX10	HTA11_99999970781_79442	Human	Colorectum	MSS	6.08e-03	-2.79e-01	0.294
1352	COX10	HTA11_99999971662_82457	Human	Colorectum	MSS	1.94e-12	-4.59e-01	0.3859
1352	COX10	HTA11_99999974143_84620	Human	Colorectum	MSS	5.15e-11	-4.73e-01	0.3005
1352	COX10	A001-C-207	Human	Colorectum	FAP	1.13e-03	-4.07e-01	0.1278
1352	COX10	A015-C-203	Human	Colorectum	FAP	9.65e-27	-4.82e-01	-0.1294
1352	COX10	A015-C-204	Human	Colorectum	FAP	8.29e-06	-3.83e-01	-0.0228
1352	COX10	A014-C-040	Human	Colorectum	FAP	1.49e-02	-4.87e-01	-0.1184
1352	COX10	A002-C-201	Human	Colorectum	FAP	1.60e-11	-3.95e-01	0.0324
1352	COX10	A002-C-203	Human	Colorectum	FAP	1.55e-05	-3.31e-01	0.2786
1352	COX10	A001-C-119	Human	Colorectum	FAP	5.19e-08	-5.18e-01	-0.1557
1352	COX10	A001-C-108	Human	Colorectum	FAP	1.81e-16	-4.05e-01	-0.0272
1352	COX10	A002-C-205	Human	Colorectum	FAP	5.70e-20	-5.72e-01	-0.1236
1352	COX10	A001-C-104	Human	Colorectum	FAP	2.80e-05	-3.58e-01	0.0184
1352	COX10	A015-C-005	Human	Colorectum	FAP	6.24e-04	-3.65e-01	-0.0336

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias

∗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:0006091	Colorectum	AD	generation of precursor metabolites and energy	209/3918	490/18723	3.17e-28	6.61e-25	209
GO:0009060	Colorectum	AD	aerobic respiration	108/3918	189/18723	9.14e-28	1.43e-24	108
GO:0045333	Colorectum	AD	cellular respiration	119/3918	230/18723	3.21e-25	4.02e-22	119
GO:0015980	Colorectum	AD	energy derivation by oxidation of organic compounds	143/3918	318/18723	2.78e-22	2.49e-19	143
GO:00090601	Colorectum	SER	aerobic respiration	96/2897	189/18723	5.53e-30	1.70e-26	96
GO:00453331	Colorectum	SER	cellular respiration	103/2897	230/18723	2.35e-26	3.61e-23	103
GO:00060911	Colorectum	SER	generation of precursor metabolites and energy	168/2897	490/18723	1.39e-25	1.70e-22	168
GO:00159801	Colorectum	SER	energy derivation by oxidation of organic compounds	119/2897	318/18723	5.28e-22	4.62e-19	119
GO:00090602	Colorectum	MSS	aerobic respiration	98/3467	189/18723	3.35e-25	1.05e-21	98
GO:00060912	Colorectum	MSS	generation of precursor metabolites and energy	186/3467	490/18723	1.14e-24	2.15e-21	186
GO:00453332	Colorectum	MSS	cellular respiration	107/3467	230/18723	1.64e-22	2.05e-19	107
GO:00159802	Colorectum	MSS	energy derivation by oxidation of organic compounds	131/3467	318/18723	2.60e-21	2.70e-18	131
GO:00060914	Colorectum	FAP	generation of precursor metabolites and energy	128/2622	490/18723	5.58e-13	4.28e-10	128
GO:00159804	Colorectum	FAP	energy derivation by oxidation of organic compounds	85/2622	318/18723	1.36e-09	2.77e-07	85
GO:00090604	Colorectum	FAP	aerobic respiration	57/2622	189/18723	7.02e-09	1.02e-06	57
GO:00453334	Colorectum	FAP	cellular respiration	65/2622	230/18723	1.13e-08	1.33e-06	65
GO:00060915	Colorectum	CRC	generation of precursor metabolites and energy	80/2078	490/18723	2.55e-04	4.16e-03	80
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

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa00190	Colorectum	AD	Oxidative phosphorylation	86/2092	134/8465	2.47e-22	2.76e-20	1.76e-20	86
hsa04714	Colorectum	AD	Thermogenesis	120/2092	232/8465	2.76e-19	1.16e-17	7.37e-18	120
hsa001901	Colorectum	AD	Oxidative phosphorylation	86/2092	134/8465	2.47e-22	2.76e-20	1.76e-20	86
hsa047141	Colorectum	AD	Thermogenesis	120/2092	232/8465	2.76e-19	1.16e-17	7.37e-18	120
hsa001902	Colorectum	SER	Oxidative phosphorylation	79/1580	134/8465	1.98e-25	1.64e-23	1.19e-23	79
hsa047142	Colorectum	SER	Thermogenesis	106/1580	232/8465	1.15e-21	6.34e-20	4.61e-20	106
hsa001903	Colorectum	SER	Oxidative phosphorylation	79/1580	134/8465	1.98e-25	1.64e-23	1.19e-23	79
hsa047143	Colorectum	SER	Thermogenesis	106/1580	232/8465	1.15e-21	6.34e-20	4.61e-20	106
hsa001904	Colorectum	MSS	Oxidative phosphorylation	79/1875	134/8465	1.89e-20	7.90e-19	4.84e-19	79
hsa047144	Colorectum	MSS	Thermogenesis	113/1875	232/8465	1.52e-19	4.62e-18	2.83e-18	113
hsa001905	Colorectum	MSS	Oxidative phosphorylation	79/1875	134/8465	1.89e-20	7.90e-19	4.84e-19	79
hsa047145	Colorectum	MSS	Thermogenesis	113/1875	232/8465	1.52e-19	4.62e-18	2.83e-18	113
hsa047148	Colorectum	FAP	Thermogenesis	70/1404	232/8465	1.38e-07	3.08e-06	1.87e-06	70
hsa001908	Colorectum	FAP	Oxidative phosphorylation	44/1404	134/8465	2.56e-06	4.28e-05	2.60e-05	44
hsa047149	Colorectum	FAP	Thermogenesis	70/1404	232/8465	1.38e-07	3.08e-06	1.87e-06	70
hsa001909	Colorectum	FAP	Oxidative phosphorylation	44/1404	134/8465	2.56e-06	4.28e-05	2.60e-05	44
hsa00190210	Esophagus	ESCC	Oxidative phosphorylation	104/4205	134/8465	2.04e-11	2.98e-10	1.53e-10	104
hsa04714211	Esophagus	ESCC	Thermogenesis	163/4205	232/8465	9.22e-11	1.14e-09	5.86e-10	163
hsa012405	Esophagus	ESCC	Biosynthesis of cofactors	97/4205	153/8465	3.88e-04	1.35e-03	6.94e-04	97
hsa0019038	Esophagus	ESCC	Oxidative phosphorylation	104/4205	134/8465	2.04e-11	2.98e-10	1.53e-10	104

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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

COX10

SNV

Missense_Mutation

c.22N>T

p.Leu8Phe

p.L8F

Q12887

protein_coding

tolerated_low_confidence(0.2)

benign(0)

TCGA-GM-A2D9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

COX10

SNV

Missense_Mutation

novel

c.900N>C

p.Trp300Cys

p.W300C

Q12887

protein_coding

deleterious(0)

probably_damaging(0.93)

TCGA-OL-A5RW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

COX10

insertion

Frame_Shift_Ins

novel

c.969dupT

p.Pro324SerfsTer12

p.P324Sfs*12

Q12887

protein_coding

TCGA-BH-A0BV-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

COX10

insertion

Nonsense_Mutation

novel

c.325_326insAGTAGATTGGACTTGATGATTGTTAA

p.Leu109Ter

p.L109*

Q12887

protein_coding

TCGA-BH-A0HK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

COX10

deletion

Frame_Shift_Del

novel

c.201delN

p.His68ThrfsTer5

p.H68Tfs*5

Q12887

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

COX10

SNV

Missense_Mutation

novel

c.197N>A

p.Arg66Lys

p.R66K

Q12887

protein_coding

tolerated_low_confidence(0.37)

benign(0)

TCGA-C5-A1M9-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

COX10

SNV

Missense_Mutation

c.824N>T

p.Thr275Ile

p.T275I

Q12887

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AA-3672-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

COX10

SNV

Missense_Mutation

c.847N>C

p.Ala283Pro

p.A283P

Q12887

protein_coding

tolerated(0.06)

possibly_damaging(0.726)

TCGA-AD-6895-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Unknown

COX10

SNV

Missense_Mutation

rs764489645

c.922N>A

p.Asp308Asn

p.D308N

Q12887

protein_coding

tolerated(0.06)

benign(0.092)

TCGA-AZ-4315-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

COX10

SNV

Missense_Mutation

rs746158624

c.172N>T

p.Arg58Cys

p.R58C

Q12887

protein_coding

deleterious_low_confidence(0.04)

possibly_damaging(0.65)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

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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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