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: MCCC1

Gene summary for MCCC1

Gene summary.

Gene information	Species	Human
	Gene symbol	MCCC1
	Gene ID	56922
	Gene name	methylcrotonyl-CoA carboxylase subunit 1
	Gene Alias	MCC-B
	Cytomap	3q27.1
	Gene Type	protein-coding
	GO ID	GO:0006082
	UniProtAcc	Q68D27

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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
56922	MCCC1	CCI_1	Human	Cervix	CC	1.61e-04	5.37e-01	0.528
56922	MCCC1	CCI_2	Human	Cervix	CC	1.26e-12	9.90e-01	0.5249
56922	MCCC1	CCI_3	Human	Cervix	CC	4.03e-08	6.17e-01	0.516
56922	MCCC1	LZE2T	Human	Esophagus	ESCC	1.44e-04	6.74e-01	0.082
56922	MCCC1	LZE4T	Human	Esophagus	ESCC	8.06e-10	2.68e-01	0.0811
56922	MCCC1	LZE7T	Human	Esophagus	ESCC	1.86e-07	3.88e-01	0.0667
56922	MCCC1	LZE8T	Human	Esophagus	ESCC	7.83e-06	1.30e-01	0.067
56922	MCCC1	LZE20T	Human	Esophagus	ESCC	4.90e-02	1.78e-01	0.0662
56922	MCCC1	LZE22T	Human	Esophagus	ESCC	1.73e-03	5.27e-01	0.068
56922	MCCC1	LZE24T	Human	Esophagus	ESCC	5.26e-30	8.07e-01	0.0596
56922	MCCC1	LZE21T	Human	Esophagus	ESCC	2.01e-09	4.25e-01	0.0655
56922	MCCC1	P1T-E	Human	Esophagus	ESCC	2.99e-06	5.67e-01	0.0875
56922	MCCC1	P2T-E	Human	Esophagus	ESCC	1.89e-65	1.09e+00	0.1177
56922	MCCC1	P4T-E	Human	Esophagus	ESCC	1.09e-31	7.71e-01	0.1323
56922	MCCC1	P5T-E	Human	Esophagus	ESCC	3.09e-09	1.09e-01	0.1327
56922	MCCC1	P8T-E	Human	Esophagus	ESCC	2.43e-26	5.30e-01	0.0889
56922	MCCC1	P10T-E	Human	Esophagus	ESCC	2.88e-49	8.60e-01	0.116
56922	MCCC1	P11T-E	Human	Esophagus	ESCC	4.44e-13	4.70e-01	0.1426
56922	MCCC1	P12T-E	Human	Esophagus	ESCC	6.31e-106	2.25e+00	0.1122
56922	MCCC1	P15T-E	Human	Esophagus	ESCC	2.51e-29	7.01e-01	0.1149

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
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

∗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:00067906	Esophagus	ESCC	sulfur compound metabolic process	201/8552	339/18723	2.64e-07	3.94e-06	201
GO:00067671	Esophagus	ESCC	water-soluble vitamin metabolic process	41/8552	59/18723	1.84e-04	1.17e-03	41
GO:00067661	Esophagus	ESCC	vitamin metabolic process	67/8552	106/18723	2.03e-04	1.28e-03	67
GO:00442827	Esophagus	ESCC	small molecule catabolic process	201/8552	376/18723	1.35e-03	6.41e-03	201
GO:00463953	Liver	NAFLD	carboxylic acid catabolic process	73/1882	236/18723	4.16e-19	1.22e-15	73
GO:00160544	Liver	NAFLD	organic acid catabolic process	73/1882	240/18723	1.20e-18	2.34e-15	73
GO:00442825	Liver	NAFLD	small molecule catabolic process	91/1882	376/18723	8.96e-16	1.31e-12	91
GO:0009063	Liver	NAFLD	cellular amino acid catabolic process	36/1882	110/18723	6.56e-11	1.99e-08	36
GO:00065203	Liver	NAFLD	cellular amino acid metabolic process	63/1882	284/18723	1.14e-09	2.17e-07	63
GO:00067904	Liver	NAFLD	sulfur compound metabolic process	58/1882	339/18723	3.79e-05	9.38e-04	58
GO:004428211	Liver	Cirrhotic	small molecule catabolic process	151/4634	376/18723	2.20e-11	1.34e-09	151
GO:001605411	Liver	Cirrhotic	organic acid catabolic process	104/4634	240/18723	1.91e-10	9.53e-09	104
GO:004639511	Liver	Cirrhotic	carboxylic acid catabolic process	102/4634	236/18723	3.41e-10	1.63e-08	102
GO:000679011	Liver	Cirrhotic	sulfur compound metabolic process	129/4634	339/18723	3.06e-08	1.04e-06	129
GO:00090631	Liver	Cirrhotic	cellular amino acid catabolic process	49/4634	110/18723	4.47e-06	7.42e-05	49
GO:000652011	Liver	Cirrhotic	cellular amino acid metabolic process	103/4634	284/18723	8.88e-06	1.30e-04	103
GO:000679021	Liver	HCC	sulfur compound metabolic process	212/7958	339/18723	5.60e-14	3.39e-12	212
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

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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
hsa002806	Liver	NAFLD	Valine, leucine and isoleucine degradation	20/1043	48/8465	3.03e-07	1.65e-05	1.33e-05	20
hsa0028011	Liver	NAFLD	Valine, leucine and isoleucine degradation	20/1043	48/8465	3.03e-07	1.65e-05	1.33e-05	20
hsa0028021	Liver	Cirrhotic	Valine, leucine and isoleucine degradation	32/2530	48/8465	1.45e-07	2.02e-06	1.24e-06	32
hsa0028031	Liver	Cirrhotic	Valine, leucine and isoleucine degradation	32/2530	48/8465	1.45e-07	2.02e-06	1.24e-06	32
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

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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

MCCC1

SNV

Missense_Mutation

novel

c.892N>T

p.Val298Leu

p.V298L

Q96RQ3

protein_coding

tolerated(0.91)

benign(0.009)

TCGA-A8-A07Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unspecific

Exemestane

MCCC1

SNV

Missense_Mutation

novel

c.1008G>C

p.Met336Ile

p.M336I

Q96RQ3

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-C8-A8HQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MCCC1

SNV

Missense_Mutation

rs569042803

c.197N>A

p.Arg66His

p.R66H

Q96RQ3

protein_coding

deleterious(0.02)

possibly_damaging(0.485)

TCGA-D8-A1XY-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

tamoxiphen

MCCC1

insertion

Frame_Shift_Ins

novel

c.116_117insT

p.Met39IlefsTer42

p.M39Ifs*42

Q96RQ3

protein_coding

TCGA-A1-A0SQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

MCCC1

SNV

Missense_Mutation

novel

c.1258G>A

p.Val420Ile

p.V420I

Q96RQ3

protein_coding

deleterious(0.04)

possibly_damaging(0.802)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MCCC1

SNV

Missense_Mutation

rs746161844

c.650T>C

p.Ile217Thr

p.I217T

Q96RQ3

protein_coding

tolerated(0.07)

probably_damaging(0.976)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MCCC1

SNV

Missense_Mutation

novel

c.273G>A

p.Met91Ile

p.M91I

Q96RQ3

protein_coding

deleterious(0.02)

possibly_damaging(0.752)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MCCC1

SNV

Missense_Mutation

novel

c.717C>A

p.Phe239Leu

p.F239L

Q96RQ3

protein_coding

deleterious(0)

probably_damaging(0.934)

TCGA-C5-A8YR-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MCCC1

SNV

Missense_Mutation

novel

c.1438N>A

p.Glu480Lys

p.E480K

Q96RQ3

protein_coding

tolerated(0.81)

benign(0.003)

TCGA-VS-A9U7-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MCCC1

SNV

Missense_Mutation

novel

c.732N>A

p.Met244Ile

p.M244I

Q96RQ3

protein_coding

tolerated(0.05)

benign(0.093)

TCGA-XS-A8TJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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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