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: SOD2

Gene summary for SOD2

Gene summary.

Gene information	Species	Human
	Gene symbol	SOD2
	Gene ID	6648
	Gene name	superoxide dismutase 2
	Gene Alias	GClnc1
	Cytomap	6q25.3
	Gene Type	protein-coding
	GO ID	GO:0000302
	UniProtAcc	P04179

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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
6648	SOD2	GSM4909281	Human	Breast	IDC	6.29e-34	-1.09e+00	0.21
6648	SOD2	GSM4909282	Human	Breast	IDC	4.57e-25	-6.50e-01	-0.0288
6648	SOD2	GSM4909285	Human	Breast	IDC	7.13e-46	-1.35e+00	0.21
6648	SOD2	GSM4909286	Human	Breast	IDC	6.00e-45	-1.36e+00	0.1081
6648	SOD2	GSM4909287	Human	Breast	IDC	2.09e-21	-8.11e-01	0.2057
6648	SOD2	GSM4909288	Human	Breast	IDC	4.22e-04	-8.15e-01	0.0988
6648	SOD2	GSM4909289	Human	Breast	IDC	2.94e-09	-1.26e+00	0.1064
6648	SOD2	GSM4909290	Human	Breast	IDC	1.02e-24	-1.09e+00	0.2096
6648	SOD2	GSM4909291	Human	Breast	IDC	6.04e-28	-1.33e+00	0.1753
6648	SOD2	GSM4909292	Human	Breast	IDC	2.26e-03	-1.10e+00	0.1236
6648	SOD2	GSM4909293	Human	Breast	IDC	1.00e-40	-1.27e+00	0.1581
6648	SOD2	GSM4909294	Human	Breast	IDC	8.46e-51	-1.38e+00	0.2022
6648	SOD2	GSM4909295	Human	Breast	IDC	2.92e-11	-9.15e-01	0.0898
6648	SOD2	GSM4909296	Human	Breast	IDC	2.00e-53	-1.44e+00	0.1524
6648	SOD2	GSM4909297	Human	Breast	IDC	3.08e-53	-1.45e+00	0.1517
6648	SOD2	GSM4909298	Human	Breast	IDC	7.80e-48	-1.39e+00	0.1551
6648	SOD2	GSM4909299	Human	Breast	IDC	3.03e-17	-5.78e-01	0.035
6648	SOD2	GSM4909300	Human	Breast	IDC	1.72e-08	-7.39e-01	0.0334
6648	SOD2	GSM4909301	Human	Breast	IDC	8.15e-47	-1.36e+00	0.1577
6648	SOD2	GSM4909302	Human	Breast	IDC	4.21e-40	-1.27e+00	0.1545

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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
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:00971939	Breast	Precancer	intrinsic apoptotic signaling pathway	59/1080	288/18723	8.07e-18	3.60e-15	59
GO:20012339	Breast	Precancer	regulation of apoptotic signaling pathway	65/1080	356/18723	7.70e-17	3.17e-14	65
GO:20012429	Breast	Precancer	regulation of intrinsic apoptotic signaling pathway	41/1080	164/18723	6.48e-16	2.31e-13	41
GO:00069799	Breast	Precancer	response to oxidative stress	70/1080	446/18723	1.59e-14	4.26e-12	70
GO:00362939	Breast	Precancer	response to decreased oxygen levels	53/1080	322/18723	4.09e-12	6.84e-10	53
GO:00016669	Breast	Precancer	response to hypoxia	51/1080	307/18723	7.33e-12	1.11e-09	51
GO:00704829	Breast	Precancer	response to oxygen levels	55/1080	347/18723	7.47e-12	1.11e-09	55
GO:00621979	Breast	Precancer	cellular response to chemical stress	51/1080	337/18723	2.40e-10	2.34e-08	51
GO:20012349	Breast	Precancer	negative regulation of apoptotic signaling pathway	39/1080	224/18723	5.35e-10	4.77e-08	39
GO:00003029	Breast	Precancer	response to reactive oxygen species	38/1080	222/18723	1.47e-09	1.23e-07	38
GO:20012439	Breast	Precancer	negative regulation of intrinsic apoptotic signaling pathway	23/1080	98/18723	5.82e-09	4.45e-07	23
GO:00709979	Breast	Precancer	neuron death	50/1080	361/18723	7.75e-09	5.70e-07	50
GO:00514029	Breast	Precancer	neuron apoptotic process	38/1080	246/18723	2.68e-08	1.75e-06	38
GO:00345999	Breast	Precancer	cellular response to oxidative stress	42/1080	288/18723	2.78e-08	1.79e-06	42
GO:00086378	Breast	Precancer	apoptotic mitochondrial changes	23/1080	107/18723	3.44e-08	2.12e-06	23
GO:00425429	Breast	Precancer	response to hydrogen peroxide	26/1080	146/18723	2.52e-07	1.26e-05	26
GO:19021758	Breast	Precancer	regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	11/1080	29/18723	2.95e-07	1.44e-05	11
GO:00100389	Breast	Precancer	response to metal ion	47/1080	373/18723	3.88e-07	1.79e-05	47
GO:00988698	Breast	Precancer	cellular oxidant detoxification	20/1080	101/18723	1.07e-06	4.18e-05	20
GO:19012149	Breast	Precancer	regulation of neuron death	41/1080	319/18723	1.27e-06	4.80e-05	41

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0501616	Breast	Precancer	Huntington disease	98/684	306/8465	2.85e-35	2.25e-33	1.72e-33	98
hsa0520818	Breast	Precancer	Chemical carcinogenesis - reactive oxygen species	68/684	223/8465	3.61e-23	1.14e-21	8.73e-22	68
hsa0541718	Breast	Precancer	Lipid and atherosclerosis	37/684	215/8465	7.64e-06	9.29e-05	7.12e-05	37
hsa0501617	Breast	Precancer	Huntington disease	98/684	306/8465	2.85e-35	2.25e-33	1.72e-33	98
hsa0520819	Breast	Precancer	Chemical carcinogenesis - reactive oxygen species	68/684	223/8465	3.61e-23	1.14e-21	8.73e-22	68
hsa0541719	Breast	Precancer	Lipid and atherosclerosis	37/684	215/8465	7.64e-06	9.29e-05	7.12e-05	37
hsa0501623	Breast	IDC	Huntington disease	103/867	306/8465	5.14e-30	4.17e-28	3.12e-28	103
hsa0520824	Breast	IDC	Chemical carcinogenesis - reactive oxygen species	71/867	223/8465	2.55e-19	7.53e-18	5.63e-18	71
hsa0541724	Breast	IDC	Lipid and atherosclerosis	35/867	215/8465	3.67e-03	2.29e-02	1.71e-02	35
hsa0501633	Breast	IDC	Huntington disease	103/867	306/8465	5.14e-30	4.17e-28	3.12e-28	103
hsa0520834	Breast	IDC	Chemical carcinogenesis - reactive oxygen species	71/867	223/8465	2.55e-19	7.53e-18	5.63e-18	71
hsa0541734	Breast	IDC	Lipid and atherosclerosis	35/867	215/8465	3.67e-03	2.29e-02	1.71e-02	35
hsa0501643	Breast	DCIS	Huntington disease	101/846	306/8465	1.54e-29	1.24e-27	9.13e-28	101
hsa0520843	Breast	DCIS	Chemical carcinogenesis - reactive oxygen species	70/846	223/8465	2.82e-19	8.29e-18	6.10e-18	70
hsa0541744	Breast	DCIS	Lipid and atherosclerosis	34/846	215/8465	4.50e-03	2.46e-02	1.82e-02	34
hsa0501653	Breast	DCIS	Huntington disease	101/846	306/8465	1.54e-29	1.24e-27	9.13e-28	101
hsa0520853	Breast	DCIS	Chemical carcinogenesis - reactive oxygen species	70/846	223/8465	2.82e-19	8.29e-18	6.10e-18	70
hsa0541754	Breast	DCIS	Lipid and atherosclerosis	34/846	215/8465	4.50e-03	2.46e-02	1.82e-02	34
hsa0520820	Cervix	CC	Chemical carcinogenesis - reactive oxygen species	92/1267	223/8465	4.71e-22	5.09e-20	3.01e-20	92
hsa0501618	Cervix	CC	Huntington disease	94/1267	306/8465	8.49e-13	3.06e-11	1.81e-11	94

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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

SOD2

SNV

Missense_Mutation

c.329N>A

p.Gly110Asp

p.G110D

protein_coding

deleterious(0.04)

probably_damaging(1)

TCGA-FP-7916-01

Stomach

stomach adenocarcinoma

Male

>=65

III/IV

Chemotherapy

xeloda

SOD2

SNV

Missense_Mutation

c.409G>A

p.Ala137Thr

p.A137T

protein_coding

tolerated(0.28)

benign(0.007)

TCGA-VQ-A8P2-01

Stomach

stomach adenocarcinoma

Male

>=65

III/IV

Unspecific

Complete Response

SOD2

insertion

Frame_Shift_Ins

novel

c.555_556insCTACAATA

p.Glu186LeufsTer3

p.E186Lfs*3

protein_coding

TCGA-FY-A40L-01

Thyroid

thyroid carcinoma

Female

<65

I/II

Hormone Therapy

levothyroxine

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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
6648	SOD2	ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE		cyclophosphamide	CYCLOPHOSPHAMIDE
6648	SOD2	ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE		asparaginase	ASPARAGINASE	27019981
6648	SOD2	ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE		heroin	DIACETYLMORPHINE	29459008
6648	SOD2	ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE		ANTIOXIDANT		12007958
6648	SOD2	ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE		valproic acid
6648	SOD2	ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE		paclitaxel	PACLITAXEL	25495407
6648	SOD2	ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE		methotrexate	METHOTREXATE	25330300

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