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: SURF1

Gene summary for SURF1

Gene summary.

Gene information	Species	Human
	Gene symbol	SURF1
	Gene ID	6834
	Gene name	SURF1 cytochrome c oxidase assembly factor
	Gene Alias	CMT4K
	Cytomap	9q34.2
	Gene Type	protein-coding
	GO ID	GO:0006091
	UniProtAcc	A0A087WYS9

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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
6834	SURF1	HTA11_3410_2000001011	Human	Colorectum	AD	2.41e-02	1.42e-01	0.0155
6834	SURF1	HTA11_2487_2000001011	Human	Colorectum	SER	6.28e-08	3.73e-01	-0.1808
6834	SURF1	HTA11_347_2000001011	Human	Colorectum	AD	3.21e-13	3.71e-01	-0.1954
6834	SURF1	HTA11_2112_2000001011	Human	Colorectum	SER	1.40e-06	5.98e-01	-0.2196
6834	SURF1	HTA11_3361_2000001011	Human	Colorectum	AD	5.61e-06	2.83e-01	-0.1207
6834	SURF1	HTA11_83_2000001011	Human	Colorectum	SER	1.48e-02	3.10e-01	-0.1526
6834	SURF1	HTA11_696_2000001011	Human	Colorectum	AD	3.12e-12	3.62e-01	-0.1464
6834	SURF1	HTA11_866_2000001011	Human	Colorectum	AD	1.47e-03	1.84e-01	-0.1001
6834	SURF1	HTA11_1391_2000001011	Human	Colorectum	AD	2.93e-09	3.73e-01	-0.059
6834	SURF1	HTA11_5212_2000001011	Human	Colorectum	AD	1.66e-02	3.46e-01	-0.2061
6834	SURF1	HTA11_5216_2000001011	Human	Colorectum	SER	4.63e-04	4.78e-01	-0.1462
6834	SURF1	HTA11_546_2000001011	Human	Colorectum	AD	3.21e-05	3.38e-01	-0.0842
6834	SURF1	HTA11_866_3004761011	Human	Colorectum	AD	1.69e-07	2.83e-01	0.096
6834	SURF1	HTA11_10623_2000001011	Human	Colorectum	AD	8.48e-07	4.33e-01	-0.0177
6834	SURF1	HTA11_6801_2000001011	Human	Colorectum	SER	1.45e-04	3.79e-01	0.0171
6834	SURF1	HTA11_10711_2000001011	Human	Colorectum	AD	1.87e-03	2.03e-01	0.0338
6834	SURF1	HTA11_7696_3000711011	Human	Colorectum	AD	2.74e-08	2.69e-01	0.0674
6834	SURF1	HTA11_6818_2000001021	Human	Colorectum	AD	3.37e-02	3.07e-01	0.0588
6834	SURF1	HTA11_99999971662_82457	Human	Colorectum	MSS	5.57e-08	2.72e-01	0.3859
6834	SURF1	HTA11_99999974143_84620	Human	Colorectum	MSS	7.59e-12	3.49e-01	0.3005

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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
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
Prostate		BPH: Benign Prostatic Hyperplasia
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
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:19026002	Colorectum	MSS	proton transmembrane transport	57/3467	157/18723	1.00e-07	4.81e-06	57
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:0033108110	Esophagus	ESCC	mitochondrial respiratory chain complex assembly	83/8552	93/18723	9.56e-19	1.05e-16	83
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:001700413	Esophagus	ESCC	cytochrome complex assembly	34/8552	36/18723	5.08e-10	1.31e-08	34
GO:000853512	Esophagus	ESCC	respiratory chain complex IV assembly	24/8552	26/18723	6.87e-07	8.99e-06	24
GO:003361712	Esophagus	ESCC	mitochondrial cytochrome c oxidase assembly	21/8552	22/18723	8.75e-07	1.13e-05	21
GO:190260018	Esophagus	ESCC	proton transmembrane transport	88/8552	157/18723	5.62e-03	2.10e-02	88
GO:000609112	Liver	Cirrhotic	generation of precursor metabolites and energy	238/4634	490/18723	6.85e-31	1.07e-27	238
GO:002290012	Liver	Cirrhotic	electron transport chain	111/4634	175/18723	1.94e-27	1.52e-24	111
GO:00090607	Liver	Cirrhotic	aerobic respiration	109/4634	189/18723	3.88e-22	1.62e-19	109
GO:00453337	Liver	Cirrhotic	cellular respiration	122/4634	230/18723	2.15e-20	6.43e-18	122
GO:001598012	Liver	Cirrhotic	energy derivation by oxidation of organic compounds	154/4634	318/18723	3.11e-20	8.87e-18	154
GO:00331087	Liver	Cirrhotic	mitochondrial respiratory chain complex assembly	64/4634	93/18723	3.85e-19	7.79e-17	64
GO:0017004	Liver	Cirrhotic	cytochrome complex assembly	22/4634	36/18723	3.92e-06	6.70e-05	22
GO:0033617	Liver	Cirrhotic	mitochondrial cytochrome c oxidase assembly	14/4634	22/18723	1.27e-04	1.25e-03	14
GO:0008535	Liver	Cirrhotic	respiratory chain complex IV assembly	15/4634	26/18723	3.43e-04	2.93e-03	15

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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

SURF1

insertion

Frame_Shift_Ins

novel

c.651_652insACCCAACGTAAAGGCCATACAGGACT

p.Pro218ThrfsTer59

p.P218Tfs*59

Q15526

protein_coding

TCGA-B6-A0IA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SURF1

SNV

Missense_Mutation

rs782044026

c.251N>A

p.Arg84Gln

p.R84Q

Q15526

protein_coding

deleterious(0.01)

probably_damaging(0.913)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SURF1

SNV

Missense_Mutation

novel

c.667G>C

p.Glu223Gln

p.E223Q

Q15526

protein_coding

tolerated(0.09)

benign(0.248)

TCGA-C5-A2LX-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SURF1

SNV

Missense_Mutation

novel

c.425N>T

p.Pro142Leu

p.P142L

Q15526

protein_coding

deleterious(0)

possibly_damaging(0.811)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

SURF1

SNV

Missense_Mutation

novel

c.689N>A

p.Arg230Gln

p.R230Q

Q15526

protein_coding

deleterious(0)

probably_damaging(0.928)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

SURF1

SNV

Missense_Mutation

rs782024654

c.269T>C

p.Leu90Pro

p.L90P

Q15526

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AX-A2HJ-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SURF1

SNV

Missense_Mutation

rs374365243

c.250N>T

p.Arg84Trp

p.R84W

Q15526

protein_coding

tolerated(0.1)

benign(0.333)

TCGA-AX-A3FT-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SURF1

SNV

Missense_Mutation

c.647N>C

p.Phe216Ser

p.F216S

Q15526

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-B5-A11E-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SURF1

SNV

Missense_Mutation

novel

c.886N>A

p.Gly296Arg

p.G296R

Q15526

protein_coding

tolerated(1)

benign(0)

TCGA-EO-A22U-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SURF1

SNV

Missense_Mutation

rs782453666

c.184N>A

p.Leu62Ile

p.L62I

Q15526

protein_coding

deleterious(0.04)

benign(0.076)

TCGA-EO-A22U-01

Endometrium

uterine corpus endometrioid carcinoma

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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