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: PFKM

Gene summary for PFKM

Gene summary.

Gene information	Species	Human
	Gene symbol	PFKM
	Gene ID	5213
	Gene name	phosphofructokinase, muscle
	Gene Alias	ATP-PFK
	Cytomap	12q13.11
	Gene Type	protein-coding
	GO ID	GO:0000272
	UniProtAcc	A0A024R0Y5

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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
5213	PFKM	LZE24T	Human	Esophagus	ESCC	1.46e-08	9.04e-02	0.0596
5213	PFKM	P1T-E	Human	Esophagus	ESCC	4.95e-02	1.14e-01	0.0875
5213	PFKM	P2T-E	Human	Esophagus	ESCC	7.87e-20	3.88e-01	0.1177
5213	PFKM	P4T-E	Human	Esophagus	ESCC	9.75e-11	2.02e-01	0.1323
5213	PFKM	P5T-E	Human	Esophagus	ESCC	3.61e-05	-2.13e-02	0.1327
5213	PFKM	P8T-E	Human	Esophagus	ESCC	6.26e-16	1.51e-01	0.0889
5213	PFKM	P9T-E	Human	Esophagus	ESCC	3.47e-03	-1.41e-02	0.1131
5213	PFKM	P10T-E	Human	Esophagus	ESCC	1.52e-14	2.89e-01	0.116
5213	PFKM	P11T-E	Human	Esophagus	ESCC	3.94e-03	9.95e-02	0.1426
5213	PFKM	P12T-E	Human	Esophagus	ESCC	7.32e-21	2.74e-01	0.1122
5213	PFKM	P15T-E	Human	Esophagus	ESCC	3.39e-14	2.18e-01	0.1149
5213	PFKM	P16T-E	Human	Esophagus	ESCC	4.71e-25	4.05e-01	0.1153
5213	PFKM	P17T-E	Human	Esophagus	ESCC	5.77e-10	3.07e-01	0.1278
5213	PFKM	P19T-E	Human	Esophagus	ESCC	1.62e-03	2.06e-01	0.1662
5213	PFKM	P21T-E	Human	Esophagus	ESCC	9.37e-10	2.90e-01	0.1617
5213	PFKM	P22T-E	Human	Esophagus	ESCC	4.19e-21	2.42e-01	0.1236
5213	PFKM	P23T-E	Human	Esophagus	ESCC	7.15e-09	3.35e-01	0.108
5213	PFKM	P24T-E	Human	Esophagus	ESCC	2.31e-13	3.97e-01	0.1287
5213	PFKM	P26T-E	Human	Esophagus	ESCC	9.42e-25	5.44e-01	0.1276
5213	PFKM	P27T-E	Human	Esophagus	ESCC	3.43e-15	2.70e-01	0.1055

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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
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:000917920	Esophagus	ESCC	purine ribonucleoside diphosphate metabolic process	63/8552	103/18723	1.10e-03	5.52e-03	63
GO:00442827	Esophagus	ESCC	small molecule catabolic process	201/8552	376/18723	1.35e-03	6.41e-03	201
GO:004693919	Esophagus	ESCC	nucleotide phosphorylation	61/8552	101/18723	2.03e-03	9.08e-03	61
GO:004603119	Esophagus	ESCC	ADP metabolic process	55/8552	90/18723	2.27e-03	9.99e-03	55
GO:000609019	Esophagus	ESCC	pyruvate metabolic process	63/8552	106/18723	2.98e-03	1.24e-02	63
GO:000930617	Esophagus	ESCC	protein secretion	190/8552	359/18723	3.22e-03	1.34e-02	190
GO:000616519	Esophagus	ESCC	nucleoside diphosphate phosphorylation	59/8552	99/18723	3.65e-03	1.49e-02	59
GO:003559217	Esophagus	ESCC	establishment of protein localization to extracellular region	190/8552	360/18723	3.77e-03	1.53e-02	190
GO:00442751	Esophagus	ESCC	cellular carbohydrate catabolic process	27/8552	40/18723	4.39e-03	1.73e-02	27
GO:007169210	Esophagus	ESCC	protein localization to extracellular region	193/8552	368/18723	5.01e-03	1.92e-02	193
GO:00616203	Esophagus	ESCC	glycolytic process through glucose-6-phosphate	10/8552	12/18723	8.94e-03	3.12e-02	10
GO:005070810	Esophagus	ESCC	regulation of protein secretion	142/8552	268/18723	9.31e-03	3.24e-02	142
GO:000609620	Esophagus	ESCC	glycolytic process	48/8552	81/18723	9.54e-03	3.30e-02	48
GO:000675720	Esophagus	ESCC	ATP generation from ADP	48/8552	82/18723	1.29e-02	4.27e-02	48
GO:005071416	Esophagus	ESCC	positive regulation of protein secretion	76/8552	137/18723	1.32e-02	4.31e-02	76
GO:000609118	Oral cavity	OSCC	generation of precursor metabolites and energy	286/7305	490/18723	1.45e-18	1.71e-16	286
GO:190495119	Oral cavity	OSCC	positive regulation of establishment of protein localization	196/7305	319/18723	2.89e-16	2.20e-14	196
GO:005122219	Oral cavity	OSCC	positive regulation of protein transport	187/7305	303/18723	7.37e-16	5.49e-14	187
GO:001598018	Oral cavity	OSCC	energy derivation by oxidation of organic compounds	190/7305	318/18723	4.10e-14	2.26e-12	190
GO:004603420	Oral cavity	OSCC	ATP metabolic process	166/7305	277/18723	1.16e-12	5.12e-11	166

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0120023	Esophagus	ESCC	Carbon metabolism	79/4205	115/8465	2.50e-05	1.21e-04	6.22e-05	79
hsa0406629	Esophagus	ESCC	HIF-1 signaling pathway	75/4205	109/8465	3.66e-05	1.68e-04	8.60e-05	75
hsa0523018	Esophagus	ESCC	Central carbon metabolism in cancer	50/4205	70/8465	1.70e-04	6.62e-04	3.39e-04	50
hsa0415210	Esophagus	ESCC	AMPK signaling pathway	80/4205	121/8465	1.73e-04	6.67e-04	3.42e-04	80
hsa0491928	Esophagus	ESCC	Thyroid hormone signaling pathway	78/4205	121/8465	6.79e-04	2.23e-03	1.14e-03	78
hsa0123023	Esophagus	ESCC	Biosynthesis of amino acids	49/4205	75/8465	4.35e-03	1.12e-02	5.74e-03	49
hsa0001016	Esophagus	ESCC	Glycolysis / Gluconeogenesis	42/4205	67/8465	2.15e-02	4.78e-02	2.45e-02	42
hsa0492214	Esophagus	ESCC	Glucagon signaling pathway	64/4205	107/8465	2.18e-02	4.80e-02	2.46e-02	64
hsa0120033	Esophagus	ESCC	Carbon metabolism	79/4205	115/8465	2.50e-05	1.21e-04	6.22e-05	79
hsa04066113	Esophagus	ESCC	HIF-1 signaling pathway	75/4205	109/8465	3.66e-05	1.68e-04	8.60e-05	75
hsa0523019	Esophagus	ESCC	Central carbon metabolism in cancer	50/4205	70/8465	1.70e-04	6.62e-04	3.39e-04	50
hsa0415213	Esophagus	ESCC	AMPK signaling pathway	80/4205	121/8465	1.73e-04	6.67e-04	3.42e-04	80
hsa04919113	Esophagus	ESCC	Thyroid hormone signaling pathway	78/4205	121/8465	6.79e-04	2.23e-03	1.14e-03	78
hsa0123033	Esophagus	ESCC	Biosynthesis of amino acids	49/4205	75/8465	4.35e-03	1.12e-02	5.74e-03	49
hsa0001017	Esophagus	ESCC	Glycolysis / Gluconeogenesis	42/4205	67/8465	2.15e-02	4.78e-02	2.45e-02	42
hsa0492215	Esophagus	ESCC	Glucagon signaling pathway	64/4205	107/8465	2.18e-02	4.80e-02	2.46e-02	64
hsa030189	Oral cavity	OSCC	RNA degradation	59/3704	79/8465	2.05e-08	1.91e-07	9.70e-08	59
hsa0120014	Oral cavity	OSCC	Carbon metabolism	74/3704	115/8465	6.10e-06	3.05e-05	1.55e-05	74
hsa0523016	Oral cavity	OSCC	Central carbon metabolism in cancer	49/3704	70/8465	7.57e-06	3.59e-05	1.83e-05	49
hsa0406627	Oral cavity	OSCC	HIF-1 signaling pathway	68/3704	109/8465	6.30e-05	2.48e-04	1.26e-04	68

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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

PFKM

SNV

Missense_Mutation

c.2353C>T

p.Arg785Cys

p.R785C

P08237

protein_coding

deleterious(0.04)

probably_damaging(0.999)

TCGA-A8-A081-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PFKM

SNV

Missense_Mutation

c.1580N>C

p.Val527Ala

p.V527A

P08237

protein_coding

deleterious(0.04)

benign(0.316)

TCGA-B6-A0IH-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

PFKM

insertion

Nonsense_Mutation

novel

c.1536_1537insCTCTCATTCATTGTATAATAATGATATCTGAGATGGGGGACAGCA

p.Glu512_Gly513insLeuSerPheIleValTerTerTerTyrLeuArgTrpGlyThrAla

p.E512_G513insLSFIV***YLRWGTA

P08237

protein_coding

TCGA-AN-A0FN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PFKM

insertion

Frame_Shift_Ins

novel

c.2395_2396insGCTGT

p.Asp799GlyfsTer18

p.D799Gfs*18

P08237

protein_coding

TCGA-AN-A0FV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PFKM

insertion

Frame_Shift_Ins

novel

c.2396_2397insAGCCTGGGGC

p.Asp799GlufsTer9

p.D799Efs*9

P08237

protein_coding

TCGA-AN-A0FV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PFKM

insertion

Frame_Shift_Ins

novel

c.1601_1602insGGTCGTCACTTTT

p.Gly535ValfsTer7

p.G535Vfs*7

P08237

protein_coding

TCGA-AO-A0JF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

PFKM

SNV

Missense_Mutation

novel

c.1444N>T

p.Pro482Ser

p.P482S

P08237

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-IR-A3LK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

PFKM

SNV

Missense_Mutation

rs121918196

c.2271G>T

p.Trp757Cys

p.W757C

P08237

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AA-3854-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

PFKM

SNV

Missense_Mutation

c.506N>A

p.Arg169Gln

p.R169Q

P08237

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-AA-3977-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

PFKM

SNV

Missense_Mutation

c.842G>A

p.Arg281His

p.R281H

P08237

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AZ-6598-01

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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