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: PCCB

Gene summary for PCCB

Gene summary.

Gene information	Species	Human
	Gene symbol	PCCB
	Gene ID	5096
	Gene name	propionyl-CoA carboxylase subunit beta
	Gene Alias	PCCB
	Cytomap	3q22.3
	Gene Type	protein-coding
	GO ID	GO:0006082
	UniProtAcc	P05166

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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
5096	PCCB	HTA11_347_2000001011	Human	Colorectum	AD	8.25e-03	2.40e-01	-0.1954
5096	PCCB	HTA11_1391_2000001011	Human	Colorectum	AD	1.16e-03	4.03e-01	-0.059
5096	PCCB	HTA11_99999965062_69753	Human	Colorectum	MSI-H	1.93e-03	7.65e-01	0.3487
5096	PCCB	A015-C-203	Human	Colorectum	FAP	2.96e-03	-1.11e-01	-0.1294
5096	PCCB	A001-C-108	Human	Colorectum	FAP	2.13e-04	-1.41e-01	-0.0272
5096	PCCB	A015-C-104	Human	Colorectum	FAP	1.08e-03	-1.34e-01	-0.1899
5096	PCCB	A002-C-016	Human	Colorectum	FAP	9.99e-04	-1.33e-01	0.0521
5096	PCCB	A002-C-116	Human	Colorectum	FAP	2.80e-02	-1.37e-01	-0.0452
5096	PCCB	F034	Human	Colorectum	FAP	2.20e-02	-1.39e-01	-0.0665
5096	PCCB	LZE4T	Human	Esophagus	ESCC	4.73e-07	2.36e-01	0.0811
5096	PCCB	LZE7T	Human	Esophagus	ESCC	8.59e-08	5.29e-01	0.0667
5096	PCCB	LZE8T	Human	Esophagus	ESCC	2.10e-04	2.61e-01	0.067
5096	PCCB	LZE20T	Human	Esophagus	ESCC	1.01e-03	1.94e-01	0.0662
5096	PCCB	LZE22D1	Human	Esophagus	HGIN	3.34e-02	1.47e-01	0.0595
5096	PCCB	LZE22T	Human	Esophagus	ESCC	2.44e-04	4.31e-01	0.068
5096	PCCB	LZE24T	Human	Esophagus	ESCC	1.77e-11	3.92e-01	0.0596
5096	PCCB	P1T-E	Human	Esophagus	ESCC	3.24e-10	3.30e-01	0.0875
5096	PCCB	P2T-E	Human	Esophagus	ESCC	1.16e-26	5.33e-01	0.1177
5096	PCCB	P4T-E	Human	Esophagus	ESCC	6.32e-34	8.64e-01	0.1323
5096	PCCB	P5T-E	Human	Esophagus	ESCC	6.06e-32	6.57e-01	0.1327

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ

∗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:0044282	Colorectum	AD	small molecule catabolic process	118/3918	376/18723	1.05e-06	3.55e-05	118
GO:0009062	Colorectum	AD	fatty acid catabolic process	41/3918	100/18723	4.02e-06	1.09e-04	41
GO:0016042	Colorectum	AD	lipid catabolic process	97/3918	320/18723	4.31e-05	7.56e-04	97
GO:0006631	Colorectum	AD	fatty acid metabolic process	114/3918	390/18723	5.58e-05	9.44e-04	114
GO:0072329	Colorectum	AD	monocarboxylic acid catabolic process	44/3918	122/18723	8.05e-05	1.28e-03	44
GO:0016054	Colorectum	AD	organic acid catabolic process	73/3918	240/18723	3.20e-04	3.81e-03	73
GO:0044242	Colorectum	AD	cellular lipid catabolic process	66/3918	214/18723	3.96e-04	4.50e-03	66
GO:0046395	Colorectum	AD	carboxylic acid catabolic process	70/3918	236/18723	9.06e-04	8.71e-03	70
GO:0046459	Colorectum	AD	short-chain fatty acid metabolic process	8/3918	15/18723	5.67e-03	3.64e-02	8
GO:00090623	Colorectum	FAP	fatty acid catabolic process	31/2622	100/18723	9.77e-06	2.85e-04	31
GO:00066313	Colorectum	FAP	fatty acid metabolic process	81/2622	390/18723	1.43e-04	2.24e-03	81
GO:00723293	Colorectum	FAP	monocarboxylic acid catabolic process	32/2622	122/18723	2.57e-04	3.53e-03	32
GO:00442422	Colorectum	FAP	cellular lipid catabolic process	49/2622	214/18723	2.87e-04	3.77e-03	49
GO:00442823	Colorectum	FAP	small molecule catabolic process	77/2622	376/18723	3.25e-04	4.16e-03	77
GO:00160423	Colorectum	FAP	lipid catabolic process	65/2622	320/18723	1.13e-03	1.08e-02	65
GO:00160543	Colorectum	FAP	organic acid catabolic process	50/2622	240/18723	2.30e-03	1.85e-02	50
GO:00463951	Colorectum	FAP	carboxylic acid catabolic process	48/2622	236/18723	4.53e-03	3.08e-02	48
GO:00090628	Esophagus	ESCC	fatty acid catabolic process	66/8552	100/18723	3.21e-05	2.66e-04	66
GO:00066318	Esophagus	ESCC	fatty acid metabolic process	217/8552	390/18723	4.21e-05	3.39e-04	217
GO:00723297	Esophagus	ESCC	monocarboxylic acid catabolic process	74/8552	122/18723	6.03e-04	3.27e-03	74

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa01200	Colorectum	AD	Carbon metabolism	55/2092	115/8465	5.53e-08	8.42e-07	5.37e-07	55
hsa00640	Colorectum	AD	Propanoate metabolism	18/2092	32/8465	1.33e-04	1.11e-03	7.08e-04	18
hsa00630	Colorectum	AD	Glyoxylate and dicarboxylate metabolism	14/2092	30/8465	7.25e-03	2.97e-02	1.89e-02	14
hsa012001	Colorectum	AD	Carbon metabolism	55/2092	115/8465	5.53e-08	8.42e-07	5.37e-07	55
hsa006401	Colorectum	AD	Propanoate metabolism	18/2092	32/8465	1.33e-04	1.11e-03	7.08e-04	18
hsa006301	Colorectum	AD	Glyoxylate and dicarboxylate metabolism	14/2092	30/8465	7.25e-03	2.97e-02	1.89e-02	14
hsa006302	Colorectum	MSI-H	Glyoxylate and dicarboxylate metabolism	8/797	30/8465	5.34e-03	4.94e-02	4.14e-02	8
hsa006303	Colorectum	MSI-H	Glyoxylate and dicarboxylate metabolism	8/797	30/8465	5.34e-03	4.94e-02	4.14e-02	8
hsa012006	Colorectum	FAP	Carbon metabolism	38/1404	115/8465	1.04e-05	1.44e-04	8.76e-05	38
hsa012007	Colorectum	FAP	Carbon metabolism	38/1404	115/8465	1.04e-05	1.44e-04	8.76e-05	38
hsa0120016	Esophagus	HGIN	Carbon metabolism	31/1383	115/8465	2.51e-03	2.10e-02	1.67e-02	31
hsa0120017	Esophagus	HGIN	Carbon metabolism	31/1383	115/8465	2.51e-03	2.10e-02	1.67e-02	31
hsa0120023	Esophagus	ESCC	Carbon metabolism	79/4205	115/8465	2.50e-05	1.21e-04	6.22e-05	79
hsa002809	Esophagus	ESCC	Valine, leucine and isoleucine degradation	34/4205	48/8465	2.34e-03	6.54e-03	3.35e-03	34
hsa006306	Esophagus	ESCC	Glyoxylate and dicarboxylate metabolism	21/4205	30/8465	1.95e-02	4.35e-02	2.23e-02	21
hsa0120033	Esophagus	ESCC	Carbon metabolism	79/4205	115/8465	2.50e-05	1.21e-04	6.22e-05	79
hsa0028014	Esophagus	ESCC	Valine, leucine and isoleucine degradation	34/4205	48/8465	2.34e-03	6.54e-03	3.35e-03	34
hsa0063013	Esophagus	ESCC	Glyoxylate and dicarboxylate metabolism	21/4205	30/8465	1.95e-02	4.35e-02	2.23e-02	21
hsa0064010	Liver	NAFLD	Propanoate metabolism	12/1043	32/8465	2.44e-04	4.45e-03	3.58e-03	12
hsa0120010	Liver	NAFLD	Carbon metabolism	26/1043	115/8465	1.39e-03	1.71e-02	1.38e-02	26

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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

PCCB

SNV

Missense_Mutation

c.1156N>G

p.Leu386Val

p.L386V

P05166

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.999)

TCGA-AN-A0AT-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PCCB

insertion

Frame_Shift_Ins

novel

c.1341_1342insCCTCAAGTGGTCTGCCTGCCCG

p.Thr448ProfsTer20

p.T448Pfs*20

P05166

protein_coding

TCGA-A8-A07J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

PCCB

insertion

Frame_Shift_Ins

novel

c.1343_1344insCTCCCAA

p.Val449SerfsTer14

p.V449Sfs*14

P05166

protein_coding

TCGA-A8-A07J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

PCCB

SNV

Missense_Mutation

c.979N>A

p.Pro327Thr

p.P327T

P05166

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-AA-3710-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

PCCB

SNV

Missense_Mutation

c.166N>A

p.Asp56Asn

p.D56N

P05166

protein_coding

deleterious_low_confidence(0.03)

benign(0.007)

TCGA-D5-6532-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

PCCB

SNV

Missense_Mutation

novel

c.1250N>G

p.Phe417Cys

p.F417C

P05166

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-AG-A00Y-01

Colorectum

rectum adenocarcinoma

Male

>=65

I/II

Unknown

PCCB

SNV

Missense_Mutation

novel

c.245N>A

p.Ser82Asn

p.S82N

P05166

protein_coding

deleterious_low_confidence(0.04)

benign(0.21)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

PCCB

SNV

Missense_Mutation

novel

c.714N>T

p.Lys238Asn

p.K238N

P05166

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.589)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PCCB

SNV

Missense_Mutation

rs764697873

c.1595N>A

p.Arg532His

p.R532H

P05166

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PCCB

SNV

Missense_Mutation

novel

c.415N>A

p.Ala139Thr

p.A139T

P05166

protein_coding

tolerated_low_confidence(0.38)

unknown(0)

TCGA-AJ-A23O-01

Endometrium

uterine corpus endometrioid carcinoma

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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