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: MCCC2

Gene summary for MCCC2

Gene summary.

Gene information	Species	Human
	Gene symbol	MCCC2
	Gene ID	64087
	Gene name	methylcrotonyl-CoA carboxylase subunit 2
	Gene Alias	MCCB
	Cytomap	5q13.2
	Gene Type	protein-coding
	GO ID	GO:0006082
	UniProtAcc	A0A140VK29

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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
64087	MCCC2	GSM4909286	Human	Breast	IDC	8.07e-06	-1.72e-01	0.1081
64087	MCCC2	GSM4909293	Human	Breast	IDC	3.69e-11	3.20e-01	0.1581
64087	MCCC2	GSM4909302	Human	Breast	IDC	8.43e-19	5.41e-01	0.1545
64087	MCCC2	GSM4909303	Human	Breast	IDC	3.27e-02	3.12e-01	0.0438
64087	MCCC2	GSM4909304	Human	Breast	IDC	1.57e-50	8.10e-01	0.1636
64087	MCCC2	GSM4909308	Human	Breast	IDC	5.05e-07	2.31e-01	0.158
64087	MCCC2	GSM4909311	Human	Breast	IDC	3.60e-07	-7.93e-02	0.1534
64087	MCCC2	GSM4909312	Human	Breast	IDC	7.33e-03	1.30e-01	0.1552
64087	MCCC2	GSM4909319	Human	Breast	IDC	2.77e-13	1.81e-02	0.1563
64087	MCCC2	M1	Human	Breast	IDC	5.01e-06	2.94e-01	0.1577
64087	MCCC2	M5	Human	Breast	IDC	1.37e-03	4.76e-01	0.1598
64087	MCCC2	DCIS2	Human	Breast	DCIS	2.64e-32	9.95e-02	0.0085
64087	MCCC2	LZE2T	Human	Esophagus	ESCC	6.46e-08	4.93e-01	0.082
64087	MCCC2	LZE4T	Human	Esophagus	ESCC	1.53e-10	2.91e-01	0.0811
64087	MCCC2	LZE5T	Human	Esophagus	ESCC	8.84e-04	1.93e-01	0.0514
64087	MCCC2	LZE7T	Human	Esophagus	ESCC	5.22e-06	3.76e-01	0.0667
64087	MCCC2	LZE8T	Human	Esophagus	ESCC	9.81e-05	2.02e-01	0.067
64087	MCCC2	LZE20T	Human	Esophagus	ESCC	1.35e-05	1.77e-01	0.0662
64087	MCCC2	LZE21D1	Human	Esophagus	HGIN	1.23e-04	2.47e-01	0.0632
64087	MCCC2	LZE24T	Human	Esophagus	ESCC	1.64e-16	6.36e-01	0.0596

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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
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:004428221	Liver	HCC	small molecule catabolic process	225/7958	376/18723	6.50e-12	2.80e-10	225
GO:001605421	Liver	HCC	organic acid catabolic process	152/7958	240/18723	5.11e-11	1.92e-09	152
GO:00463952	Liver	HCC	carboxylic acid catabolic process	149/7958	236/18723	1.11e-10	3.87e-09	149
GO:00338652	Liver	HCC	nucleoside bisphosphate metabolic process	88/7958	128/18723	1.63e-09	4.78e-08	88
GO:00338752	Liver	HCC	ribonucleoside bisphosphate metabolic process	88/7958	128/18723	1.63e-09	4.78e-08	88
GO:00340322	Liver	HCC	purine nucleoside bisphosphate metabolic process	88/7958	128/18723	1.63e-09	4.78e-08	88
GO:00065202	Liver	HCC	cellular amino acid metabolic process	167/7958	284/18723	1.91e-08	4.56e-07	167
GO:00090632	Liver	HCC	cellular amino acid catabolic process	70/7958	110/18723	6.12e-06	7.52e-05	70
GO:0015936	Liver	HCC	coenzyme A metabolic process	14/7958	18/18723	2.57e-03	1.23e-02	14
GO:000675318	Oral cavity	OSCC	nucleoside phosphate metabolic process	247/7305	497/18723	6.28e-07	8.96e-06	247
GO:000911719	Oral cavity	OSCC	nucleotide metabolic process	243/7305	489/18723	7.80e-07	1.09e-05	243
GO:001969319	Oral cavity	OSCC	ribose phosphate metabolic process	199/7305	396/18723	2.97e-06	3.64e-05	199
GO:000925919	Oral cavity	OSCC	ribonucleotide metabolic process	189/7305	385/18723	3.18e-05	2.87e-04	189
GO:007252120	Oral cavity	OSCC	purine-containing compound metabolic process	199/7305	416/18723	1.34e-04	9.53e-04	199
GO:000915020	Oral cavity	OSCC	purine ribonucleotide metabolic process	178/7305	368/18723	1.45e-04	1.02e-03	178
GO:000616320	Oral cavity	OSCC	purine nucleotide metabolic process	188/7305	396/18723	3.31e-04	2.04e-03	188
GO:00442826	Oral cavity	OSCC	small molecule catabolic process	174/7305	376/18723	2.25e-03	1.00e-02	174
GO:00338654	Oral cavity	OSCC	nucleoside bisphosphate metabolic process	66/7305	128/18723	2.58e-03	1.13e-02	66
GO:00338754	Oral cavity	OSCC	ribonucleoside bisphosphate metabolic process	66/7305	128/18723	2.58e-03	1.13e-02	66
GO:00340324	Oral cavity	OSCC	purine nucleoside bisphosphate metabolic process	66/7305	128/18723	2.58e-03	1.13e-02	66

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa002809	Esophagus	ESCC	Valine, leucine and isoleucine degradation	34/4205	48/8465	2.34e-03	6.54e-03	3.35e-03	34
hsa0028014	Esophagus	ESCC	Valine, leucine and isoleucine degradation	34/4205	48/8465	2.34e-03	6.54e-03	3.35e-03	34
hsa0028041	Liver	HCC	Valine, leucine and isoleucine degradation	41/4020	48/8465	4.84e-08	7.05e-07	3.92e-07	41
hsa0028051	Liver	HCC	Valine, leucine and isoleucine degradation	41/4020	48/8465	4.84e-08	7.05e-07	3.92e-07	41
hsa002808	Oral cavity	OSCC	Valine, leucine and isoleucine degradation	30/3704	48/8465	6.75e-03	1.57e-02	7.99e-03	30
hsa0028013	Oral cavity	OSCC	Valine, leucine and isoleucine degradation	30/3704	48/8465	6.75e-03	1.57e-02	7.99e-03	30
hsa0028022	Oral cavity	LP	Valine, leucine and isoleucine degradation	22/2418	48/8465	7.98e-03	3.02e-02	1.95e-02	22
hsa0028032	Oral cavity	LP	Valine, leucine and isoleucine degradation	22/2418	48/8465	7.98e-03	3.02e-02	1.95e-02	22
hsa002807	Prostate	Tumor	Valine, leucine and isoleucine degradation	20/1791	48/8465	1.03e-03	4.59e-03	2.84e-03	20
hsa0028012	Prostate	Tumor	Valine, leucine and isoleucine degradation	20/1791	48/8465	1.03e-03	4.59e-03	2.84e-03	20

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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

MCCC2

SNV

Missense_Mutation

novel

c.760N>A

p.Glu254Lys

p.E254K

Q9HCC0

protein_coding

tolerated_low_confidence(0.29)

possibly_damaging(0.597)

TCGA-A7-A56D-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

MCCC2

SNV

Missense_Mutation

c.855N>A

p.His285Gln

p.H285Q

Q9HCC0

protein_coding

tolerated_low_confidence(0.58)

benign(0.139)

TCGA-AA-3511-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

MCCC2

SNV

Missense_Mutation

novel

c.1060N>G

p.Thr354Ala

p.T354A

Q9HCC0

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.908)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

MCCC2

SNV

Missense_Mutation

c.257G>T

p.Arg86Ile

p.R86I

Q9HCC0

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.999)

TCGA-CA-6718-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

MCCC2

SNV

Missense_Mutation

c.1460A>C

p.Lys487Thr

p.K487T

Q9HCC0

protein_coding

deleterious_low_confidence(0.01)

benign(0.371)

TCGA-CA-6718-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

MCCC2

SNV

Missense_Mutation

c.242N>G

p.Leu81Arg

p.L81R

Q9HCC0

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.978)

TCGA-D5-6928-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

MCCC2

SNV

Missense_Mutation

rs752866557

c.518C>T

p.Ser173Leu

p.S173L

Q9HCC0

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-F4-6703-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

MCCC2

SNV

Missense_Mutation

rs772144978

c.166C>T

p.Leu56Phe

p.L56F

Q9HCC0

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.959)

TCGA-G4-6303-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Chemotherapy

5-fu

MCCC2

insertion

Frame_Shift_Ins

novel

c.1142_1143insA

p.Thr385TyrfsTer27

p.T385Yfs*27

Q9HCC0

protein_coding

TCGA-AA-3947-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

MCCC2

insertion

Frame_Shift_Ins

novel

c.1034_1035insAG

p.Glu346ValfsTer11

p.E346Vfs*11

Q9HCC0

protein_coding

TCGA-AM-5820-01

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

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