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: PC

Gene summary for PC

Gene summary.

Gene information	Species	Human
	Gene symbol	PC
	Gene ID	5091
	Gene name	pyruvate carboxylase
	Gene Alias	PCB
	Cytomap	11q13.2
	Gene Type	protein-coding
	GO ID	GO:0005975
	UniProtAcc	A0A024R5C5

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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
5091	PC	LZE4T	Human	Esophagus	ESCC	1.99e-06	2.40e-01	0.0811
5091	PC	LZE24T	Human	Esophagus	ESCC	1.99e-06	8.82e-02	0.0596
5091	PC	LZE21T	Human	Esophagus	ESCC	2.38e-03	3.68e-01	0.0655
5091	PC	P2T-E	Human	Esophagus	ESCC	3.22e-06	6.93e-02	0.1177
5091	PC	P4T-E	Human	Esophagus	ESCC	1.05e-09	1.10e-01	0.1323
5091	PC	P5T-E	Human	Esophagus	ESCC	4.85e-02	4.69e-02	0.1327
5091	PC	P8T-E	Human	Esophagus	ESCC	4.74e-04	9.31e-02	0.0889
5091	PC	P9T-E	Human	Esophagus	ESCC	3.79e-14	2.80e-01	0.1131
5091	PC	P10T-E	Human	Esophagus	ESCC	1.41e-03	6.28e-02	0.116
5091	PC	P11T-E	Human	Esophagus	ESCC	3.75e-04	1.97e-01	0.1426
5091	PC	P15T-E	Human	Esophagus	ESCC	5.49e-28	6.82e-01	0.1149
5091	PC	P16T-E	Human	Esophagus	ESCC	6.55e-09	1.18e-01	0.1153
5091	PC	P20T-E	Human	Esophagus	ESCC	8.95e-07	1.32e-01	0.1124
5091	PC	P21T-E	Human	Esophagus	ESCC	3.28e-19	5.13e-01	0.1617
5091	PC	P22T-E	Human	Esophagus	ESCC	1.04e-02	3.64e-02	0.1236
5091	PC	P23T-E	Human	Esophagus	ESCC	3.45e-02	4.02e-02	0.108
5091	PC	P24T-E	Human	Esophagus	ESCC	7.89e-05	9.29e-02	0.1287
5091	PC	P26T-E	Human	Esophagus	ESCC	2.23e-03	2.30e-02	0.1276
5091	PC	P27T-E	Human	Esophagus	ESCC	1.89e-04	1.33e-01	0.1055
5091	PC	P28T-E	Human	Esophagus	ESCC	4.82e-06	1.58e-01	0.1149

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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

∗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:00226139	Breast	Precancer	ribonucleoprotein complex biogenesis	79/1080	463/18723	2.11e-18	1.03e-15	79
GO:00718269	Breast	Precancer	ribonucleoprotein complex subunit organization	48/1080	227/18723	2.68e-15	8.45e-13	48
GO:00226189	Breast	Precancer	ribonucleoprotein complex assembly	47/1080	220/18723	3.47e-15	1.03e-12	47
GO:00069799	Breast	Precancer	response to oxidative stress	70/1080	446/18723	1.59e-14	4.26e-12	70
GO:00083809	Breast	Precancer	RNA splicing	65/1080	434/18723	1.27e-12	2.53e-10	65
GO:00064179	Breast	Precancer	regulation of translation	67/1080	468/18723	4.71e-12	7.64e-10	67
GO:00457279	Breast	Precancer	positive regulation of translation	32/1080	136/18723	5.89e-12	9.27e-10	32
GO:00003759	Breast	Precancer	RNA splicing, via transesterification reactions	52/1080	324/18723	1.74e-11	2.22e-09	52
GO:00485459	Breast	Precancer	response to steroid hormone	53/1080	339/18723	3.07e-11	3.66e-09	53
GO:00003779	Breast	Precancer	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	51/1080	320/18723	3.55e-11	4.04e-09	51
GO:00003989	Breast	Precancer	mRNA splicing, via spliceosome	51/1080	320/18723	3.55e-11	4.04e-09	51
GO:00342509	Breast	Precancer	positive regulation of cellular amide metabolic process	33/1080	162/18723	1.72e-10	1.77e-08	33
GO:00621979	Breast	Precancer	cellular response to chemical stress	51/1080	337/18723	2.40e-10	2.34e-08	51
GO:00160329	Breast	Precancer	viral process	58/1080	415/18723	3.42e-10	3.16e-08	58
GO:00003029	Breast	Precancer	response to reactive oxygen species	38/1080	222/18723	1.47e-09	1.23e-07	38
GO:00190589	Breast	Precancer	viral life cycle	47/1080	317/18723	2.42e-09	1.99e-07	47
GO:00458619	Breast	Precancer	negative regulation of proteolysis	50/1080	351/18723	2.99e-09	2.39e-07	50
GO:00319608	Breast	Precancer	response to corticosteroid	30/1080	167/18723	2.50e-08	1.65e-06	30
GO:00345999	Breast	Precancer	cellular response to oxidative stress	42/1080	288/18723	2.78e-08	1.79e-06	42
GO:00104989	Breast	Precancer	proteasomal protein catabolic process	58/1080	490/18723	1.54e-07	8.05e-06	58

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0002014	Esophagus	ESCC	Citrate cycle (TCA cycle)	27/4205	30/8465	3.48e-06	1.94e-05	9.95e-06	27
hsa0120023	Esophagus	ESCC	Carbon metabolism	79/4205	115/8465	2.50e-05	1.21e-04	6.22e-05	79
hsa0123023	Esophagus	ESCC	Biosynthesis of amino acids	49/4205	75/8465	4.35e-03	1.12e-02	5.74e-03	49
hsa0062023	Esophagus	ESCC	Pyruvate metabolism	32/4205	47/8465	8.11e-03	1.94e-02	9.94e-03	32
hsa0002015	Esophagus	ESCC	Citrate cycle (TCA cycle)	27/4205	30/8465	3.48e-06	1.94e-05	9.95e-06	27
hsa0120033	Esophagus	ESCC	Carbon metabolism	79/4205	115/8465	2.50e-05	1.21e-04	6.22e-05	79
hsa0123033	Esophagus	ESCC	Biosynthesis of amino acids	49/4205	75/8465	4.35e-03	1.12e-02	5.74e-03	49
hsa0062033	Esophagus	ESCC	Pyruvate metabolism	32/4205	47/8465	8.11e-03	1.94e-02	9.94e-03	32
hsa0120010	Liver	NAFLD	Carbon metabolism	26/1043	115/8465	1.39e-03	1.71e-02	1.38e-02	26
hsa0120011	Liver	NAFLD	Carbon metabolism	26/1043	115/8465	1.39e-03	1.71e-02	1.38e-02	26
hsa0120021	Liver	Cirrhotic	Carbon metabolism	64/2530	115/8465	6.37e-09	1.18e-07	7.26e-08	64
hsa006208	Liver	Cirrhotic	Pyruvate metabolism	29/2530	47/8465	5.90e-06	5.95e-05	3.67e-05	29
hsa0002010	Liver	Cirrhotic	Citrate cycle (TCA cycle)	21/2530	30/8465	6.56e-06	6.24e-05	3.84e-05	21
hsa012304	Liver	Cirrhotic	Biosynthesis of amino acids	35/2530	75/8465	1.54e-03	7.83e-03	4.83e-03	35
hsa0120031	Liver	Cirrhotic	Carbon metabolism	64/2530	115/8465	6.37e-09	1.18e-07	7.26e-08	64
hsa0062011	Liver	Cirrhotic	Pyruvate metabolism	29/2530	47/8465	5.90e-06	5.95e-05	3.67e-05	29
hsa0002011	Liver	Cirrhotic	Citrate cycle (TCA cycle)	21/2530	30/8465	6.56e-06	6.24e-05	3.84e-05	21
hsa0123011	Liver	Cirrhotic	Biosynthesis of amino acids	35/2530	75/8465	1.54e-03	7.83e-03	4.83e-03	35
hsa0120041	Liver	HCC	Carbon metabolism	89/4020	115/8465	3.92e-11	6.56e-10	3.65e-10	89
hsa0002021	Liver	HCC	Citrate cycle (TCA cycle)	28/4020	30/8465	1.08e-07	1.44e-06	8.02e-07	28

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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

SNV

Missense_Mutation

novel

c.1378N>A

p.Ala460Thr

p.A460T

P11498

protein_coding

deleterious(0.01)

benign(0.108)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SNV

Missense_Mutation

novel

c.1726N>G

p.Ser576Ala

p.S576A

P11498

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AR-A256-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

SNV

Missense_Mutation

c.619N>C

p.Val207Leu

p.V207L

P11498

protein_coding

deleterious(0.01)

possibly_damaging(0.822)

TCGA-B6-A0I6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SNV

Missense_Mutation

c.584C>T

p.Ala195Val

p.A195V

P11498

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-B6-A0IB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

SNV

Missense_Mutation

rs119103242

c.1748N>A

p.Arg583His

p.R583H

P11498

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SNV

Missense_Mutation

c.1217G>A

p.Arg406His

p.R406H

P11498

protein_coding

deleterious(0)

probably_damaging(0.985)

TCGA-C8-A138-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

SNV

Missense_Mutation

c.730N>T

p.His244Tyr

p.H244Y

P11498

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SNV

Missense_Mutation

c.1848N>A

p.Met616Ile

p.M616I

P11498

protein_coding

deleterious(0.01)

benign(0.059)

TCGA-EW-A1PD-01

Breast

breast invasive carcinoma

Male

<65

I/II

Chemotherapy

docetaxel

SNV

Missense_Mutation

novel

c.151N>A

p.Arg51Ser

p.R51S

P11498

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-EW-A6SC-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

aromatase

SNV

Missense_Mutation

c.2395N>A

p.Asp799Asn

p.D799N

P11498

protein_coding

tolerated(0.18)

probably_damaging(0.967)

TCGA-DS-A0VK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

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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
5091	PC	ENZYME, CLINICALLY ACTIONABLE		AMPHOTERICIN B		2015823
5091	PC	ENZYME, CLINICALLY ACTIONABLE		CORTISOL	HYDROCORTISONE	942746

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