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: SDHC

Gene summary for SDHC

Gene summary.

Gene information	Species	Human
	Gene symbol	SDHC
	Gene ID	6391
	Gene name	succinate dehydrogenase complex subunit C
	Gene Alias	CYB560
	Cytomap	1q23.3
	Gene Type	protein-coding
	GO ID	GO:0006091
	UniProtAcc	Q99643

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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
6391	SDHC	GSM4909318	Human	Breast	IDC	4.22e-04	4.25e-01	0.2031
6391	SDHC	GSM4909319	Human	Breast	IDC	1.50e-32	1.29e-02	0.1563
6391	SDHC	GSM4909320	Human	Breast	IDC	2.22e-04	-1.83e-01	0.1575
6391	SDHC	GSM4909321	Human	Breast	IDC	2.47e-21	3.87e-01	0.1559
6391	SDHC	brca1	Human	Breast	Precancer	1.25e-06	3.26e-01	-0.0338
6391	SDHC	brca2	Human	Breast	Precancer	2.93e-13	3.87e-01	-0.024
6391	SDHC	brca3	Human	Breast	Precancer	3.13e-08	2.55e-01	-0.0263
6391	SDHC	M2	Human	Breast	IDC	4.52e-02	2.12e-01	0.21
6391	SDHC	NCCBC11	Human	Breast	DCIS	8.65e-10	4.98e-01	0.1232
6391	SDHC	NCCBC14	Human	Breast	DCIS	9.89e-06	1.26e-01	0.2021
6391	SDHC	NCCBC2	Human	Breast	DCIS	8.09e-03	-1.50e-01	0.1554
6391	SDHC	NCCBC5	Human	Breast	DCIS	1.96e-13	1.73e-01	0.2046
6391	SDHC	P1	Human	Breast	IDC	1.23e-15	-2.79e-01	0.1527
6391	SDHC	P2	Human	Breast	IDC	4.86e-05	3.04e-01	0.21
6391	SDHC	DCIS2	Human	Breast	DCIS	8.82e-52	7.72e-02	0.0085
6391	SDHC	HTA11_1938_2000001011	Human	Colorectum	AD	4.19e-06	5.56e-01	-0.0811
6391	SDHC	HTA11_347_2000001011	Human	Colorectum	AD	4.25e-15	5.99e-01	-0.1954
6391	SDHC	HTA11_696_2000001011	Human	Colorectum	AD	1.03e-07	3.77e-01	-0.1464
6391	SDHC	HTA11_1391_2000001011	Human	Colorectum	AD	2.64e-04	4.94e-01	-0.059
6391	SDHC	HTA11_866_3004761011	Human	Colorectum	AD	5.12e-04	4.04e-01	0.096

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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:00460349	Breast	Precancer	ATP metabolic process	82/1080	277/18723	1.94e-36	5.19e-33	82
GO:00061199	Breast	Precancer	oxidative phosphorylation	53/1080	141/18723	1.15e-29	2.04e-26	53
GO:00090608	Breast	Precancer	aerobic respiration	58/1080	189/18723	5.69e-27	7.62e-24	58
GO:00060918	Breast	Precancer	generation of precursor metabolites and energy	94/1080	490/18723	1.54e-25	1.64e-22	94
GO:00453338	Breast	Precancer	cellular respiration	59/1080	230/18723	5.97e-23	5.32e-20	59
GO:00159808	Breast	Precancer	energy derivation by oxidation of organic compounds	70/1080	318/18723	8.33e-23	6.37e-20	70
GO:00196468	Breast	Precancer	aerobic electron transport chain	34/1080	87/18723	3.95e-20	2.64e-17	34
GO:00427738	Breast	Precancer	ATP synthesis coupled electron transport	35/1080	95/18723	1.08e-19	5.76e-17	35
GO:00427758	Breast	Precancer	mitochondrial ATP synthesis coupled electron transport	35/1080	95/18723	1.08e-19	5.76e-17	35
GO:00229048	Breast	Precancer	respiratory electron transport chain	35/1080	114/18723	8.51e-17	3.26e-14	35
GO:00229008	Breast	Precancer	electron transport chain	42/1080	175/18723	1.37e-15	4.59e-13	42
GO:004603414	Breast	IDC	ATP metabolic process	85/1434	277/18723	6.42e-30	1.82e-26	85
GO:000611913	Breast	IDC	oxidative phosphorylation	56/1434	141/18723	1.87e-26	3.53e-23	56
GO:000906013	Breast	IDC	aerobic respiration	61/1434	189/18723	4.42e-23	6.27e-20	61
GO:000609113	Breast	IDC	generation of precursor metabolites and energy	103/1434	490/18723	1.53e-21	1.74e-18	103
GO:004533313	Breast	IDC	cellular respiration	62/1434	230/18723	5.98e-19	4.25e-16	62
GO:004277313	Breast	IDC	ATP synthesis coupled electron transport	38/1434	95/18723	1.65e-18	9.36e-16	38
GO:004277513	Breast	IDC	mitochondrial ATP synthesis coupled electron transport	38/1434	95/18723	1.65e-18	9.36e-16	38
GO:001964613	Breast	IDC	aerobic electron transport chain	36/1434	87/18723	3.48e-18	1.80e-15	36
GO:001598013	Breast	IDC	energy derivation by oxidation of organic compounds	73/1434	318/18723	8.70e-18	3.80e-15	73

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0501218	Breast	Precancer	Parkinson disease	99/684	266/8465	3.58e-42	5.65e-40	4.33e-40	99
hsa0502016	Breast	Precancer	Prion disease	95/684	273/8465	1.39e-37	1.46e-35	1.12e-35	95
hsa0501616	Breast	Precancer	Huntington disease	98/684	306/8465	2.85e-35	2.25e-33	1.72e-33	98
hsa0019016	Breast	Precancer	Oxidative phosphorylation	59/684	134/8465	6.15e-30	3.24e-28	2.48e-28	59
hsa0501016	Breast	Precancer	Alzheimer disease	103/684	384/8465	1.03e-29	4.66e-28	3.57e-28	103
hsa0501416	Breast	Precancer	Amyotrophic lateral sclerosis	98/684	364/8465	2.13e-28	8.41e-27	6.44e-27	98
hsa0502216	Breast	Precancer	Pathways of neurodegeneration - multiple diseases	112/684	476/8465	6.96e-27	2.44e-25	1.87e-25	112
hsa0520818	Breast	Precancer	Chemical carcinogenesis - reactive oxygen species	68/684	223/8465	3.61e-23	1.14e-21	8.73e-22	68
hsa0471418	Breast	Precancer	Thermogenesis	68/684	232/8465	4.40e-22	1.26e-20	9.69e-21	68
hsa0541518	Breast	Precancer	Diabetic cardiomyopathy	63/684	203/8465	5.63e-22	1.48e-20	1.14e-20	63
hsa0493216	Breast	Precancer	Non-alcoholic fatty liver disease	48/684	155/8465	6.16e-17	1.50e-15	1.15e-15	48
hsa0120012	Breast	Precancer	Carbon metabolism	18/684	115/8465	4.79e-03	2.75e-02	2.11e-02	18
hsa0501219	Breast	Precancer	Parkinson disease	99/684	266/8465	3.58e-42	5.65e-40	4.33e-40	99
hsa0502017	Breast	Precancer	Prion disease	95/684	273/8465	1.39e-37	1.46e-35	1.12e-35	95
hsa0501617	Breast	Precancer	Huntington disease	98/684	306/8465	2.85e-35	2.25e-33	1.72e-33	98
hsa0019017	Breast	Precancer	Oxidative phosphorylation	59/684	134/8465	6.15e-30	3.24e-28	2.48e-28	59
hsa0501017	Breast	Precancer	Alzheimer disease	103/684	384/8465	1.03e-29	4.66e-28	3.57e-28	103
hsa0501417	Breast	Precancer	Amyotrophic lateral sclerosis	98/684	364/8465	2.13e-28	8.41e-27	6.44e-27	98
hsa0502217	Breast	Precancer	Pathways of neurodegeneration - multiple diseases	112/684	476/8465	6.96e-27	2.44e-25	1.87e-25	112
hsa0520819	Breast	Precancer	Chemical carcinogenesis - reactive oxygen species	68/684	223/8465	3.61e-23	1.14e-21	8.73e-22	68

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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

SDHC

SNV

Missense_Mutation

c.436N>T

p.Pro146Ser

p.P146S

Q99643

protein_coding

tolerated(0.2)

benign(0.014)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SDHC

SNV

Missense_Mutation

rs769177037

c.149N>A

p.Arg50His

p.R50H

Q99643

protein_coding

tolerated(0.06)

benign(0.382)

TCGA-AX-A0IZ-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SDHC

SNV

Missense_Mutation

rs749402669

c.265G>A

p.Ala89Thr

p.A89T

Q99643

protein_coding

tolerated(0.13)

benign(0.236)

TCGA-AX-A2HD-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

SDHC

SNV

Missense_Mutation

novel

c.140G>A

p.Gly47Asp

p.G47D

Q99643

protein_coding

tolerated(0.17)

benign(0)

TCGA-B5-A1MX-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Hormone Therapy

megace

SDHC

SNV

Missense_Mutation

novel

c.275N>C

p.Leu92Pro

p.L92P

Q99643

protein_coding

deleterious(0)

possibly_damaging(0.772)

TCGA-B5-A3FA-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SDHC

SNV

Missense_Mutation

novel

c.352N>C

p.Phe118Leu

p.F118L

Q99643

protein_coding

deleterious(0.01)

benign(0.171)

TCGA-DI-A1BU-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

paclitaxel

SDHC

deletion

Frame_Shift_Del

novel

c.423delA

p.Gly142AlafsTer2

p.G142Afs*2

Q99643

protein_coding

TCGA-EY-A5W2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SDHC

SNV

Missense_Mutation

novel

c.312N>C

p.Lys104Asn

p.K104N

Q99643

protein_coding

deleterious(0.01)

possibly_damaging(0.837)

TCGA-43-7656-01

Lung

lung squamous cell carcinoma

Male

>=65

I/II

Unknown

SDHC

insertion

In_Frame_Ins

novel

c.179_179+1insTTGGTCTCTTCCCAT

p.Pro64_Met65insIleTrpSerLeuPro

p.P64_M65insIWSLP

Q99643

protein_coding

TCGA-D6-A6EP-01

Oral cavity

head & neck squamous cell carcinoma

Male

<65

III/IV

Unknown

SDHC

SNV

Missense_Mutation

c.242N>A

p.Gly81Glu

p.G81E

Q99643

protein_coding

deleterious(0.01)

probably_damaging(0.986)

TCGA-EJ-8472-01

Prostate

prostate adenocarcinoma

Male

<65

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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