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: PFKP

Gene summary for PFKP

Gene summary.

Gene information	Species	Human
	Gene symbol	PFKP
	Gene ID	5214
	Gene name	phosphofructokinase, platelet
	Gene Alias	ATP-PFK
	Cytomap	10p15.2
	Gene Type	protein-coding
	GO ID	GO:0005975
	UniProtAcc	Q01813

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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
5214	PFKP	HTA11_2487_2000001011	Human	Colorectum	SER	4.81e-04	4.21e-01	-0.1808
5214	PFKP	HTA11_1938_2000001011	Human	Colorectum	AD	7.19e-05	3.93e-01	-0.0811
5214	PFKP	HTA11_2112_2000001011	Human	Colorectum	SER	2.81e-03	6.94e-01	-0.2196
5214	PFKP	HTA11_3361_2000001011	Human	Colorectum	AD	5.35e-03	3.23e-01	-0.1207
5214	PFKP	HTA11_696_2000001011	Human	Colorectum	AD	7.72e-03	3.05e-01	-0.1464
5214	PFKP	HTA11_1391_2000001011	Human	Colorectum	AD	1.10e-07	4.42e-01	-0.059
5214	PFKP	HTA11_99999965062_69753	Human	Colorectum	MSI-H	7.22e-04	9.50e-01	0.3487
5214	PFKP	A015-C-203	Human	Colorectum	FAP	1.62e-02	-1.31e-01	-0.1294
5214	PFKP	A002-C-205	Human	Colorectum	FAP	5.90e-03	-1.74e-01	-0.1236
5214	PFKP	A015-C-104	Human	Colorectum	FAP	4.16e-02	-1.12e-01	-0.1899
5214	PFKP	A002-C-016	Human	Colorectum	FAP	4.86e-02	-1.11e-01	0.0521
5214	PFKP	A002-C-116	Human	Colorectum	FAP	1.05e-02	-1.14e-01	-0.0452
5214	PFKP	AEH-subject1	Human	Endometrium	AEH	1.61e-08	4.27e-01	-0.3059
5214	PFKP	AEH-subject2	Human	Endometrium	AEH	5.96e-10	4.24e-01	-0.2525
5214	PFKP	AEH-subject4	Human	Endometrium	AEH	2.10e-03	2.84e-01	-0.2657
5214	PFKP	EEC-subject1	Human	Endometrium	EEC	1.94e-03	3.39e-01	-0.2682
5214	PFKP	EEC-subject2	Human	Endometrium	EEC	1.12e-13	5.96e-01	-0.2607
5214	PFKP	GSM5276937	Human	Endometrium	EEC	8.69e-09	3.45e-01	-0.0897
5214	PFKP	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	1.12e-11	5.32e-01	-0.1869
5214	PFKP	GSM6177620_NYU_UCEC1_lib2_lib2	Human	Endometrium	EEC	1.41e-08	4.56e-01	-0.1875

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
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:000599614	Thyroid	PTC	monosaccharide metabolic process	115/5968	257/18723	9.36e-06	1.05e-04	115
GO:000600615	Thyroid	PTC	glucose metabolic process	90/5968	196/18723	2.54e-05	2.50e-04	90
GO:0046939110	Thyroid	PTC	nucleotide phosphorylation	52/5968	101/18723	3.25e-05	3.08e-04	52
GO:0006165110	Thyroid	PTC	nucleoside diphosphate phosphorylation	50/5968	99/18723	8.68e-05	7.22e-04	50
GO:0006096110	Thyroid	PTC	glycolytic process	42/5968	81/18723	1.47e-04	1.13e-03	42
GO:0006757110	Thyroid	PTC	ATP generation from ADP	42/5968	82/18723	2.08e-04	1.54e-03	42
GO:001605218	Thyroid	PTC	carbohydrate catabolic process	70/5968	154/18723	2.77e-04	1.97e-03	70
GO:000609020	Thyroid	PTC	pyruvate metabolic process	51/5968	106/18723	3.47e-04	2.39e-03	51
GO:00616204	Thyroid	PTC	glycolytic process through glucose-6-phosphate	9/5968	12/18723	2.72e-03	1.36e-02	9
GO:00616152	Thyroid	PTC	glycolytic process through fructose-6-phosphate	9/5968	13/18723	6.33e-03	2.79e-02	9
GO:199082310	Thyroid	PTC	response to leukemia inhibitory factor	42/5968	95/18723	7.69e-03	3.27e-02	42
GO:199083010	Thyroid	PTC	cellular response to leukemia inhibitory factor	41/5968	94/18723	1.10e-02	4.38e-02	41
GO:004603434	Thyroid	ATC	ATP metabolic process	167/6293	277/18723	5.60e-20	8.64e-18	167
GO:000609134	Thyroid	ATC	generation of precursor metabolites and energy	256/6293	490/18723	6.55e-18	7.69e-16	256
GO:001969328	Thyroid	ATC	ribose phosphate metabolic process	184/6293	396/18723	5.87e-08	1.05e-06	184
GO:000915029	Thyroid	ATC	purine ribonucleotide metabolic process	172/6293	368/18723	9.58e-08	1.64e-06	172
GO:000925928	Thyroid	ATC	ribonucleotide metabolic process	178/6293	385/18723	1.47e-07	2.39e-06	178
GO:007252128	Thyroid	ATC	purine-containing compound metabolic process	189/6293	416/18723	2.83e-07	4.29e-06	189
GO:0006753111	Thyroid	ATC	nucleoside phosphate metabolic process	219/6293	497/18723	5.92e-07	8.29e-06	219
GO:0009117112	Thyroid	ATC	nucleotide metabolic process	215/6293	489/18723	9.09e-07	1.20e-05	215

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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
hsa00010	Colorectum	AD	Glycolysis / Gluconeogenesis	34/2092	67/8465	3.63e-06	4.34e-05	2.77e-05	34
hsa04066	Colorectum	AD	HIF-1 signaling pathway	48/2092	109/8465	7.25e-06	7.84e-05	5.00e-05	48
hsa04919	Colorectum	AD	Thyroid hormone signaling pathway	51/2092	121/8465	1.71e-05	1.73e-04	1.10e-04	51
hsa05230	Colorectum	AD	Central carbon metabolism in cancer	33/2092	70/8465	3.61e-05	3.19e-04	2.03e-04	33
hsa04152	Colorectum	AD	AMPK signaling pathway	47/2092	121/8465	3.74e-04	2.82e-03	1.80e-03	47
hsa04922	Colorectum	AD	Glucagon signaling pathway	41/2092	107/8465	1.18e-03	7.75e-03	4.94e-03	41
hsa00051	Colorectum	AD	Fructose and mannose metabolism	17/2092	34/8465	1.25e-03	8.02e-03	5.12e-03	17
hsa01230	Colorectum	AD	Biosynthesis of amino acids	28/2092	75/8465	9.99e-03	3.89e-02	2.48e-02	28
hsa012001	Colorectum	AD	Carbon metabolism	55/2092	115/8465	5.53e-08	8.42e-07	5.37e-07	55
hsa000101	Colorectum	AD	Glycolysis / Gluconeogenesis	34/2092	67/8465	3.63e-06	4.34e-05	2.77e-05	34
hsa040661	Colorectum	AD	HIF-1 signaling pathway	48/2092	109/8465	7.25e-06	7.84e-05	5.00e-05	48
hsa049191	Colorectum	AD	Thyroid hormone signaling pathway	51/2092	121/8465	1.71e-05	1.73e-04	1.10e-04	51
hsa052301	Colorectum	AD	Central carbon metabolism in cancer	33/2092	70/8465	3.61e-05	3.19e-04	2.03e-04	33
hsa041521	Colorectum	AD	AMPK signaling pathway	47/2092	121/8465	3.74e-04	2.82e-03	1.80e-03	47
hsa049221	Colorectum	AD	Glucagon signaling pathway	41/2092	107/8465	1.18e-03	7.75e-03	4.94e-03	41
hsa000511	Colorectum	AD	Fructose and mannose metabolism	17/2092	34/8465	1.25e-03	8.02e-03	5.12e-03	17
hsa012301	Colorectum	AD	Biosynthesis of amino acids	28/2092	75/8465	9.99e-03	3.89e-02	2.48e-02	28
hsa049222	Colorectum	SER	Glucagon signaling pathway	38/1580	107/8465	2.57e-05	3.28e-04	2.38e-04	38
hsa012002	Colorectum	SER	Carbon metabolism	40/1580	115/8465	2.77e-05	3.41e-04	2.47e-04	40

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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

PFKP

SNV

Missense_Mutation

c.1994G>T

p.Arg665Met

p.R665M

Q01813

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PFKP

SNV

Missense_Mutation

novel

c.2048G>A

p.Arg683Lys

p.R683K

Q01813

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PFKP

SNV

Missense_Mutation

novel

c.1909A>G

p.Arg637Gly

p.R637G

Q01813

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PFKP

SNV

Missense_Mutation

c.176N>A

p.Phe59Tyr

p.F59Y

Q01813

protein_coding

tolerated(0.07)

probably_damaging(0.983)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PFKP

SNV

Missense_Mutation

rs199868194

c.2216N>T

p.Thr739Met

p.T739M

Q01813

protein_coding

deleterious(0.02)

probably_damaging(0.996)

TCGA-E2-A14R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

PFKP

SNV

Missense_Mutation

c.856N>A

p.Glu286Lys

p.E286K

Q01813

protein_coding

deleterious(0.03)

benign(0.303)

TCGA-E2-A1IN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

PFKP

SNV

Missense_Mutation

novel

c.1858N>C

p.Glu620Gln

p.E620Q

Q01813

protein_coding

tolerated(0.22)

benign(0.022)

TCGA-E9-A22E-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphane

PFKP

deletion

Frame_Shift_Del

novel

c.1598delT

p.Val533AlafsTer24

p.V533Afs*24

Q01813

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

PFKP

SNV

Missense_Mutation

novel

c.946G>A

p.Ala316Thr

p.A316T

Q01813

protein_coding

deleterious(0)

probably_damaging(0.977)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PFKP

SNV

Missense_Mutation

rs753541438

c.1333G>A

p.Ala445Thr

p.A445T

Q01813

protein_coding

tolerated(0.08)

probably_damaging(0.941)

TCGA-2W-A8YY-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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