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: MYC

Gene summary for MYC

Gene summary.

Gene information	Species	Human
	Gene symbol	MYC
	Gene ID	4609
	Gene name	MYC proto-oncogene, bHLH transcription factor
	Gene Alias	MRTL
	Cytomap	8q24.21
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	A0A087WVR4

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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
4609	MYC	GSM4909277	Human	Breast	Precancer	8.93e-08	1.05e+00	0.0177
4609	MYC	GSM4909281	Human	Breast	IDC	4.68e-02	5.67e-02	0.21
4609	MYC	GSM4909282	Human	Breast	IDC	3.58e-02	3.06e-01	-0.0288
4609	MYC	GSM4909285	Human	Breast	IDC	5.51e-13	4.26e-01	0.21
4609	MYC	GSM4909286	Human	Breast	IDC	1.85e-08	-2.05e-02	0.1081
4609	MYC	GSM4909290	Human	Breast	IDC	5.26e-05	-4.07e-01	0.2096
4609	MYC	GSM4909293	Human	Breast	IDC	8.43e-06	-3.45e-01	0.1581
4609	MYC	GSM4909294	Human	Breast	IDC	2.01e-15	-6.07e-01	0.2022
4609	MYC	GSM4909296	Human	Breast	IDC	5.64e-19	-5.92e-01	0.1524
4609	MYC	GSM4909297	Human	Breast	IDC	2.04e-04	-2.21e-01	0.1517
4609	MYC	GSM4909298	Human	Breast	IDC	6.62e-04	6.11e-02	0.1551
4609	MYC	GSM4909301	Human	Breast	IDC	5.22e-05	-3.90e-01	0.1577
4609	MYC	GSM4909302	Human	Breast	IDC	3.26e-08	-4.78e-01	0.1545
4609	MYC	GSM4909305	Human	Breast	IDC	2.76e-02	2.77e-01	0.0436
4609	MYC	GSM4909307	Human	Breast	IDC	4.27e-02	-3.42e-01	0.1569
4609	MYC	GSM4909308	Human	Breast	IDC	2.85e-03	-1.08e-01	0.158
4609	MYC	GSM4909311	Human	Breast	IDC	1.63e-11	-3.63e-01	0.1534
4609	MYC	GSM4909315	Human	Breast	IDC	2.24e-11	-5.50e-01	0.21
4609	MYC	GSM4909316	Human	Breast	IDC	1.52e-07	-6.66e-01	0.21
4609	MYC	GSM4909319	Human	Breast	IDC	1.54e-17	-4.94e-01	0.1563

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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
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:00060918	Breast	Precancer	generation of precursor metabolites and energy	94/1080	490/18723	1.54e-25	1.64e-22	94
GO:00159808	Breast	Precancer	energy derivation by oxidation of organic compounds	70/1080	318/18723	8.33e-23	6.37e-20	70
GO:00525479	Breast	Precancer	regulation of peptidase activity	71/1080	461/18723	2.72e-14	6.94e-12	71
GO:00525489	Breast	Precancer	regulation of endopeptidase activity	67/1080	432/18723	1.06e-13	2.36e-11	67
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:20001169	Breast	Precancer	regulation of cysteine-type endopeptidase activity	43/1080	235/18723	1.30e-11	1.83e-09	43
GO:00432819	Breast	Precancer	regulation of cysteine-type endopeptidase activity involved in apoptotic process	40/1080	209/18723	1.59e-11	2.07e-09	40
GO:00362948	Breast	Precancer	cellular response to decreased oxygen levels	31/1080	161/18723	2.61e-09	2.11e-07	31
GO:00714538	Breast	Precancer	cellular response to oxygen levels	32/1080	177/18723	7.32e-09	5.52e-07	32
GO:00458629	Breast	Precancer	positive regulation of proteolysis	51/1080	372/18723	7.77e-09	5.70e-07	51
GO:00714565	Breast	Precancer	cellular response to hypoxia	29/1080	151/18723	8.98e-09	6.50e-07	29
GO:00109529	Breast	Precancer	positive regulation of peptidase activity	33/1080	197/18723	3.01e-08	1.89e-06	33
GO:00432808	Breast	Precancer	positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	24/1080	129/18723	3.13e-07	1.50e-05	24
GO:00109509	Breast	Precancer	positive regulation of endopeptidase activity	29/1080	179/18723	4.23e-07	1.90e-05	29
GO:20010568	Breast	Precancer	positive regulation of cysteine-type endopeptidase activity	25/1080	148/18723	1.19e-06	4.60e-05	25
GO:00300999	Breast	Precancer	myeloid cell differentiation	45/1080	381/18723	4.00e-06	1.25e-04	45
GO:00103323	Breast	Precancer	response to gamma radiation	13/1080	56/18723	1.35e-05	3.38e-04	13
GO:00456379	Breast	Precancer	regulation of myeloid cell differentiation	28/1080	210/18723	3.05e-05	6.72e-04	28

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0513218	Breast	Precancer	Salmonella infection	49/684	249/8465	2.92e-09	6.15e-08	4.71e-08	49
hsa0516718	Breast	Precancer	Kaposi sarcoma-associated herpesvirus infection	36/684	194/8465	1.68e-06	2.53e-05	1.94e-05	36
hsa0516918	Breast	Precancer	Epstein-Barr virus infection	35/684	202/8465	1.15e-05	1.26e-04	9.64e-05	35
hsa0516618	Breast	Precancer	Human T-cell leukemia virus 1 infection	33/684	222/8465	4.29e-04	3.31e-03	2.53e-03	33
hsa0520514	Breast	Precancer	Proteoglycans in cancer	30/684	205/8465	1.00e-03	7.18e-03	5.50e-03	30
hsa0516316	Breast	Precancer	Human cytomegalovirus infection	32/684	225/8465	1.13e-03	7.57e-03	5.80e-03	32
hsa0513219	Breast	Precancer	Salmonella infection	49/684	249/8465	2.92e-09	6.15e-08	4.71e-08	49
hsa0516719	Breast	Precancer	Kaposi sarcoma-associated herpesvirus infection	36/684	194/8465	1.68e-06	2.53e-05	1.94e-05	36
hsa0516919	Breast	Precancer	Epstein-Barr virus infection	35/684	202/8465	1.15e-05	1.26e-04	9.64e-05	35
hsa0516619	Breast	Precancer	Human T-cell leukemia virus 1 infection	33/684	222/8465	4.29e-04	3.31e-03	2.53e-03	33
hsa0520515	Breast	Precancer	Proteoglycans in cancer	30/684	205/8465	1.00e-03	7.18e-03	5.50e-03	30
hsa0516317	Breast	Precancer	Human cytomegalovirus infection	32/684	225/8465	1.13e-03	7.57e-03	5.80e-03	32
hsa0513224	Breast	IDC	Salmonella infection	55/867	249/8465	2.07e-08	4.49e-07	3.36e-07	55
hsa0516922	Breast	IDC	Epstein-Barr virus infection	45/867	202/8465	3.16e-07	6.05e-06	4.52e-06	45
hsa0421824	Breast	IDC	Cellular senescence	35/867	156/8465	5.49e-06	7.43e-05	5.56e-05	35
hsa0520523	Breast	IDC	Proteoglycans in cancer	42/867	205/8465	7.69e-06	9.99e-05	7.48e-05	42
hsa0516723	Breast	IDC	Kaposi sarcoma-associated herpesvirus infection	38/867	194/8465	5.87e-05	5.96e-04	4.46e-04	38
hsa0516624	Breast	IDC	Human T-cell leukemia virus 1 infection	40/867	222/8465	2.52e-04	2.21e-03	1.66e-03	40
hsa0516324	Breast	IDC	Human cytomegalovirus infection	39/867	225/8465	6.66e-04	5.41e-03	4.05e-03	39
hsa0491916	Breast	IDC	Thyroid hormone signaling pathway	23/867	121/8465	2.45e-03	1.69e-02	1.27e-02	23

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
MYC	STM	Cervix	CC	SNHG15,FGFBP1,TNFRSF12A, etc.	1.30e-01
MYC	ASC	Colorectum	MSS	RPL30,WDR41,RNF43, etc.	4.17e-01
MYC	STM	Prostate	ADJ	EEF1G,DKK1,KRT14, etc.	3.29e-01
MYC	BAS	Prostate	BPH	EEF1G,DKK1,KRT14, etc.	3.26e-01
MYC	STM	Stomach	CAG	NFKBID,PAK1IP1,IRAK2, etc.	1.30e-01
MYC	STM	Stomach	WIM	NFKBID,PAK1IP1,IRAK2, etc.	2.49e-01

∗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

MYC

SNV

Missense_Mutation

rs147506213

c.697C>A

p.Pro233Thr

p.P233T

protein_coding

tolerated(0.22)

benign(0.003)

TCGA-B6-A0I1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MYC

SNV

Missense_Mutation

c.1291N>A

p.Glu431Lys

p.E431K

protein_coding

tolerated(0.3)

benign(0.096)

TCGA-D8-A147-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine

MYC

SNV

Missense_Mutation

c.517G>C

p.Asp173His

p.D173H

protein_coding

deleterious(0.03)

probably_damaging(0.999)

TCGA-D8-A1JK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MYC

insertion

Frame_Shift_Ins

novel

c.528_529insTATGA

p.Pro177TyrfsTer22

p.P177Yfs*22

protein_coding

TCGA-AO-A0J5-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate

zoledronic

MYC

insertion

Frame_Shift_Ins

novel

c.530_531insTCGACTACGACTCGGTGCA

p.Asn178ArgfsTer86

p.N178Rfs*86

protein_coding

TCGA-AO-A0J5-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate

zoledronic

MYC

SNV

Missense_Mutation

c.482N>T

p.Ser161Leu

p.S161L

protein_coding

deleterious(0)

probably_damaging(0.981)

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

MYC

SNV

Missense_Mutation

c.986N>T

p.Ser329Phe

p.S329F

protein_coding

tolerated(0.48)

possibly_damaging(0.622)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MYC

SNV

Missense_Mutation

c.875N>T

p.Ser292Leu

p.S292L

protein_coding

deleterious(0.04)

possibly_damaging(0.835)

TCGA-LP-A7HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MYC

SNV

Missense_Mutation

c.482C>T

p.Ser161Leu

p.S161L

protein_coding

deleterious(0)

probably_damaging(0.981)

TCGA-A6-5659-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

MYC

SNV

Missense_Mutation

c.470C>T

p.Ala157Val

p.A157V

protein_coding

deleterious(0.03)

probably_damaging(0.99)

TCGA-A6-5661-01

Colorectum

colon adenocarcinoma

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
4609	MYC	TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLE		BAY1000394
4609	MYC	TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLE		ORNITHINE DECARBOXYLASE INHIBITOR		11876528
4609	MYC	TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLE		PROTEASOME INHIBITOR		16186809
4609	MYC	TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLE		HISTONE DEACETYLASE INHIBITOR		15474507
4609	MYC	TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLE		FOLIC ACID		3479800
4609	MYC	TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLE		GLN	GLUTAMINE	16898871
4609	MYC	TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLE		AN-9	AN-9	8348968
4609	MYC	TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLE		PROTOPORPHYRIN	PROTOPORPHYRIN	9868803
4609	MYC	TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLE		POH		16439861
4609	MYC	TRANSCRIPTION FACTOR, CLINICALLY ACTIONABLE		HYPOXANTHINE	HYPOXANTHINE	3528863

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