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: COX15

Gene summary for COX15

Gene summary.

Gene information	Species	Human
	Gene symbol	COX15
	Gene ID	1355
	Gene name	cytochrome c oxidase assembly homolog COX15
	Gene Alias	CEMCOX2
	Cytomap	10q24.2
	Gene Type	protein-coding
	GO ID	GO:0006091
	UniProtAcc	Q7KZN9

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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
1355	COX15	LZE4T	Human	Esophagus	ESCC	3.25e-07	1.02e-01	0.0811
1355	COX15	LZE8T	Human	Esophagus	ESCC	1.84e-02	4.98e-02	0.067
1355	COX15	LZE20T	Human	Esophagus	ESCC	2.44e-03	5.95e-02	0.0662
1355	COX15	LZE24T	Human	Esophagus	ESCC	3.79e-15	1.59e-01	0.0596
1355	COX15	P2T-E	Human	Esophagus	ESCC	1.77e-21	4.08e-01	0.1177
1355	COX15	P4T-E	Human	Esophagus	ESCC	9.13e-20	4.79e-01	0.1323
1355	COX15	P5T-E	Human	Esophagus	ESCC	1.08e-06	1.53e-01	0.1327
1355	COX15	P8T-E	Human	Esophagus	ESCC	2.32e-09	1.37e-01	0.0889
1355	COX15	P9T-E	Human	Esophagus	ESCC	6.15e-05	2.72e-02	0.1131
1355	COX15	P11T-E	Human	Esophagus	ESCC	2.89e-03	1.18e-01	0.1426
1355	COX15	P12T-E	Human	Esophagus	ESCC	9.86e-13	2.43e-01	0.1122
1355	COX15	P15T-E	Human	Esophagus	ESCC	3.72e-11	2.30e-01	0.1149
1355	COX15	P16T-E	Human	Esophagus	ESCC	5.68e-25	3.15e-01	0.1153
1355	COX15	P17T-E	Human	Esophagus	ESCC	1.40e-05	1.31e-01	0.1278
1355	COX15	P19T-E	Human	Esophagus	ESCC	1.27e-03	2.54e-01	0.1662
1355	COX15	P20T-E	Human	Esophagus	ESCC	4.38e-09	3.14e-01	0.1124
1355	COX15	P21T-E	Human	Esophagus	ESCC	6.99e-08	1.75e-01	0.1617
1355	COX15	P22T-E	Human	Esophagus	ESCC	1.24e-10	1.38e-01	0.1236
1355	COX15	P23T-E	Human	Esophagus	ESCC	1.61e-16	2.44e-01	0.108
1355	COX15	P24T-E	Human	Esophagus	ESCC	1.34e-10	1.60e-01	0.1287

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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

∗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:0022900110	Esophagus	ESCC	electron transport chain	133/8552	175/18723	2.18e-16	1.67e-14	133
GO:0046034111	Esophagus	ESCC	ATP metabolic process	189/8552	277/18723	1.99e-14	1.04e-12	189
GO:0006119111	Esophagus	ESCC	oxidative phosphorylation	106/8552	141/18723	8.19e-13	3.63e-11	106
GO:0022904110	Esophagus	ESCC	respiratory electron transport chain	89/8552	114/18723	1.36e-12	5.80e-11	89
GO:0042773110	Esophagus	ESCC	ATP synthesis coupled electron transport	74/8552	95/18723	1.28e-10	3.77e-09	74
GO:0042775110	Esophagus	ESCC	mitochondrial ATP synthesis coupled electron transport	74/8552	95/18723	1.28e-10	3.77e-09	74
GO:001700413	Esophagus	ESCC	cytochrome complex assembly	34/8552	36/18723	5.08e-10	1.31e-08	34
GO:0019646110	Esophagus	ESCC	aerobic electron transport chain	67/8552	87/18723	2.30e-09	5.14e-08	67
GO:000853512	Esophagus	ESCC	respiratory chain complex IV assembly	24/8552	26/18723	6.87e-07	8.99e-06	24
GO:00067791	Esophagus	ESCC	porphyrin-containing compound biosynthetic process	23/8552	31/18723	1.20e-03	5.88e-03	23
GO:00330141	Esophagus	ESCC	tetrapyrrole biosynthetic process	23/8552	31/18723	1.20e-03	5.88e-03	23
GO:00461482	Esophagus	ESCC	pigment biosynthetic process	40/8552	62/18723	2.14e-03	9.54e-03	40
GO:00067832	Esophagus	ESCC	heme biosynthetic process	20/8552	27/18723	2.61e-03	1.11e-02	20
GO:190260018	Esophagus	ESCC	proton transmembrane transport	88/8552	157/18723	5.62e-03	2.10e-02	88
GO:00330132	Esophagus	ESCC	tetrapyrrole metabolic process	37/8552	59/18723	6.23e-03	2.29e-02	37
GO:00424401	Esophagus	ESCC	pigment metabolic process	50/8552	84/18723	7.34e-03	2.64e-02	50

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
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
hsa04714310	Esophagus	ESCC	Thermogenesis	163/4205	232/8465	9.22e-11	1.14e-09	5.86e-10	163
hsa0124012	Esophagus	ESCC	Biosynthesis of cofactors	97/4205	153/8465	3.88e-04	1.35e-03	6.94e-04	97
hsa0471422	Liver	HCC	Thermogenesis	170/4020	232/8465	5.36e-16	2.25e-14	1.25e-14	170
hsa0019022	Liver	HCC	Oxidative phosphorylation	103/4020	134/8465	2.39e-12	5.01e-11	2.79e-11	103
hsa012402	Liver	HCC	Biosynthesis of cofactors	103/4020	153/8465	4.67e-07	5.05e-06	2.81e-06	103
hsa0471432	Liver	HCC	Thermogenesis	170/4020	232/8465	5.36e-16	2.25e-14	1.25e-14	170
hsa0019032	Liver	HCC	Oxidative phosphorylation	103/4020	134/8465	2.39e-12	5.01e-11	2.79e-11	103
hsa012403	Liver	HCC	Biosynthesis of cofactors	103/4020	153/8465	4.67e-07	5.05e-06	2.81e-06	103
hsa0019028	Oral cavity	OSCC	Oxidative phosphorylation	88/3704	134/8465	2.15e-07	1.44e-06	7.32e-07	88
hsa0471430	Oral cavity	OSCC	Thermogenesis	138/3704	232/8465	7.67e-07	4.35e-06	2.22e-06	138
hsa012404	Oral cavity	OSCC	Biosynthesis of cofactors	88/3704	153/8465	3.84e-04	1.20e-03	6.12e-04	88
hsa00190112	Oral cavity	OSCC	Oxidative phosphorylation	88/3704	134/8465	2.15e-07	1.44e-06	7.32e-07	88
hsa04714113	Oral cavity	OSCC	Thermogenesis	138/3704	232/8465	7.67e-07	4.35e-06	2.22e-06	138
hsa0124011	Oral cavity	OSCC	Biosynthesis of cofactors	88/3704	153/8465	3.84e-04	1.20e-03	6.12e-04	88

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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

COX15

SNV

Missense_Mutation

c.586C>G

p.Leu196Val

p.L196V

Q7KZN9

protein_coding

tolerated(0.07)

possibly_damaging(0.836)

TCGA-AO-A0J6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

COX15

SNV

Missense_Mutation

novel

c.532N>A

p.Arg178Ser

p.R178S

Q7KZN9

protein_coding

tolerated(0.48)

benign(0.019)

TCGA-AR-A24H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

COX15

SNV

Missense_Mutation

c.697N>T

p.Leu233Phe

p.L233F

Q7KZN9

protein_coding

deleterious(0.03)

benign(0.35)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

COX15

SNV

Missense_Mutation

c.472C>A

p.Leu158Ile

p.L158I

Q7KZN9

protein_coding

tolerated(0.33)

benign(0.018)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

COX15

insertion

Frame_Shift_Ins

novel

c.102_103insT

p.Arg35Ter

p.R35*

Q7KZN9

protein_coding

TCGA-B6-A0IC-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

COX15

insertion

Frame_Shift_Ins

novel

c.100_101insACATGGTAAAACCCTG

p.Ile34AsnfsTer20

p.I34Nfs*20

Q7KZN9

protein_coding

TCGA-B6-A0IC-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

COX15

SNV

Missense_Mutation

c.503N>A

p.Ala168Asp

p.A168D

Q7KZN9

protein_coding

deleterious(0.02)

possibly_damaging(0.529)

TCGA-VS-A9UD-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

COX15

SNV

Missense_Mutation

c.449N>G

p.Tyr150Cys

p.Y150C

Q7KZN9

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-AA-3492-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

COX15

SNV

Missense_Mutation

novel

c.362N>C

p.Phe121Ser

p.F121S

Q7KZN9

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AA-3950-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

COX15

SNV

Missense_Mutation

c.256N>A

p.Leu86Ile

p.L86I

Q7KZN9

protein_coding

tolerated(0.26)

possibly_damaging(0.823)

TCGA-AA-A00N-01

Colorectum

colon adenocarcinoma

Male

>=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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