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: PHKG2

Gene summary for PHKG2

Gene summary.

Gene information	Species	Human
	Gene symbol	PHKG2
	Gene ID	5261
	Gene name	phosphorylase kinase catalytic subunit gamma 2
	Gene Alias	GSD9C
	Cytomap	16p11.2
	Gene Type	protein-coding
	GO ID	GO:0000271
	UniProtAcc	P15735

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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
5261	PHKG2	LZE4T	Human	Esophagus	ESCC	1.20e-10	2.78e-01	0.0811
5261	PHKG2	LZE7T	Human	Esophagus	ESCC	3.58e-09	5.80e-01	0.0667
5261	PHKG2	LZE8T	Human	Esophagus	ESCC	5.63e-12	2.97e-01	0.067
5261	PHKG2	LZE20T	Human	Esophagus	ESCC	1.83e-04	1.47e-01	0.0662
5261	PHKG2	LZE24D1	Human	Esophagus	HGIN	1.14e-02	6.38e-01	0.054
5261	PHKG2	LZE24T	Human	Esophagus	ESCC	4.43e-41	1.25e+00	0.0596
5261	PHKG2	LZE21T	Human	Esophagus	ESCC	3.67e-06	4.89e-01	0.0655
5261	PHKG2	LZE6T	Human	Esophagus	ESCC	2.06e-08	4.77e-01	0.0845
5261	PHKG2	P1T-E	Human	Esophagus	ESCC	1.06e-13	6.16e-01	0.0875
5261	PHKG2	P2T-E	Human	Esophagus	ESCC	6.43e-44	7.80e-01	0.1177
5261	PHKG2	P4T-E	Human	Esophagus	ESCC	1.40e-16	4.68e-01	0.1323
5261	PHKG2	P5T-E	Human	Esophagus	ESCC	3.23e-16	3.17e-01	0.1327
5261	PHKG2	P8T-E	Human	Esophagus	ESCC	2.80e-23	4.63e-01	0.0889
5261	PHKG2	P9T-E	Human	Esophagus	ESCC	6.55e-08	1.49e-01	0.1131
5261	PHKG2	P10T-E	Human	Esophagus	ESCC	1.20e-22	3.78e-01	0.116
5261	PHKG2	P11T-E	Human	Esophagus	ESCC	1.43e-11	4.75e-01	0.1426
5261	PHKG2	P12T-E	Human	Esophagus	ESCC	2.42e-36	7.01e-01	0.1122
5261	PHKG2	P15T-E	Human	Esophagus	ESCC	2.86e-15	2.81e-01	0.1149
5261	PHKG2	P16T-E	Human	Esophagus	ESCC	7.71e-16	3.46e-01	0.1153
5261	PHKG2	P17T-E	Human	Esophagus	ESCC	2.20e-05	2.90e-01	0.1278

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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:0006091110	Esophagus	ESCC	generation of precursor metabolites and energy	331/8552	490/18723	3.86e-23	8.45e-21	331
GO:0009896111	Esophagus	ESCC	positive regulation of catabolic process	332/8552	492/18723	4.36e-23	9.22e-21	332
GO:0031331111	Esophagus	ESCC	positive regulation of cellular catabolic process	292/8552	427/18723	8.67e-22	1.53e-19	292
GO:0015980110	Esophagus	ESCC	energy derivation by oxidation of organic compounds	220/8552	318/18723	1.20e-17	1.09e-15	220
GO:00059969	Esophagus	ESCC	monosaccharide metabolic process	159/8552	257/18723	1.11e-07	1.81e-06	159
GO:00193189	Esophagus	ESCC	hexose metabolic process	147/8552	237/18723	2.63e-07	3.94e-06	147
GO:00060069	Esophagus	ESCC	glucose metabolic process	119/8552	196/18723	1.51e-05	1.36e-04	119
GO:004346719	Esophagus	ESCC	regulation of generation of precursor metabolites and energy	81/8552	130/18723	9.58e-05	6.81e-04	81
GO:00442626	Esophagus	ESCC	cellular carbohydrate metabolic process	160/8552	283/18723	1.43e-04	9.66e-04	160
GO:00160514	Esophagus	ESCC	carbohydrate biosynthetic process	117/8552	202/18723	2.96e-04	1.79e-03	117
GO:00620129	Esophagus	ESCC	regulation of small molecule metabolic process	184/8552	334/18723	3.11e-04	1.85e-03	184
GO:001605216	Esophagus	ESCC	carbohydrate catabolic process	91/8552	154/18723	5.39e-04	2.97e-03	91
GO:00434713	Esophagus	ESCC	regulation of cellular carbohydrate catabolic process	11/8552	12/18723	1.26e-03	6.06e-03	11
GO:00109065	Esophagus	ESCC	regulation of glucose metabolic process	71/8552	119/18723	1.46e-03	6.92e-03	71
GO:00061096	Esophagus	ESCC	regulation of carbohydrate metabolic process	101/8552	178/18723	1.89e-03	8.52e-03	101
GO:00106755	Esophagus	ESCC	regulation of cellular carbohydrate metabolic process	83/8552	146/18723	4.24e-03	1.69e-02	83
GO:00442751	Esophagus	ESCC	cellular carbohydrate catabolic process	27/8552	40/18723	4.39e-03	1.73e-02	27
GO:004347010	Esophagus	ESCC	regulation of carbohydrate catabolic process	35/8552	56/18723	8.30e-03	2.94e-02	35
GO:00346372	Esophagus	ESCC	cellular carbohydrate biosynthetic process	46/8552	78/18723	1.24e-02	4.13e-02	46
GO:000609122	Liver	HCC	generation of precursor metabolites and energy	340/7958	490/18723	4.04e-34	2.85e-31	340

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa049109	Esophagus	ESCC	Insulin signaling pathway	89/4205	137/8465	1.97e-04	7.32e-04	3.75e-04	89
hsa0492214	Esophagus	ESCC	Glucagon signaling pathway	64/4205	107/8465	2.18e-02	4.80e-02	2.46e-02	64
hsa0491014	Esophagus	ESCC	Insulin signaling pathway	89/4205	137/8465	1.97e-04	7.32e-04	3.75e-04	89
hsa0492215	Esophagus	ESCC	Glucagon signaling pathway	64/4205	107/8465	2.18e-02	4.80e-02	2.46e-02	64
hsa0491041	Liver	HCC	Insulin signaling pathway	95/4020	137/8465	1.53e-07	1.97e-06	1.10e-06	95
hsa0492241	Liver	HCC	Glucagon signaling pathway	64/4020	107/8465	6.70e-03	1.87e-02	1.04e-02	64
hsa0491051	Liver	HCC	Insulin signaling pathway	95/4020	137/8465	1.53e-07	1.97e-06	1.10e-06	95
hsa0492251	Liver	HCC	Glucagon signaling pathway	64/4020	107/8465	6.70e-03	1.87e-02	1.04e-02	64
hsa049108	Oral cavity	OSCC	Insulin signaling pathway	83/3704	137/8465	4.83e-05	2.00e-04	1.02e-04	83
hsa0491013	Oral cavity	OSCC	Insulin signaling pathway	83/3704	137/8465	4.83e-05	2.00e-04	1.02e-04	83

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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

PHKG2

SNV

Missense_Mutation

c.55N>A

p.Glu19Lys

p.E19K

P15735

protein_coding

tolerated(0.07)

benign(0.38)

TCGA-A1-A0SN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

PHKG2

insertion

Frame_Shift_Ins

novel

c.470_471insT

p.Glu157AspfsTer7

p.E157Dfs*7

P15735

protein_coding

TCGA-A8-A08G-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

PHKG2

insertion

In_Frame_Ins

novel

c.471_472insCAGAGATCTATCTTTAGTGGCCTCTTCCAC

p.Glu157_Asn158insGlnArgSerIlePheSerGlyLeuPheHis

p.E157_N158insQRSIFSGLFH

P15735

protein_coding

TCGA-A8-A08G-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

PHKG2

insertion

Frame_Shift_Ins

novel

c.948_949insCTCCCCTTCCCCCA

p.Ala317LeufsTer12

p.A317Lfs*12

P15735

protein_coding

TCGA-BH-A0AY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

PHKG2

insertion

Frame_Shift_Ins

novel

c.949_950insGTCCATCATGCGGTCT

p.Ala317GlyfsTer77

p.A317Gfs*77

P15735

protein_coding

TCGA-BH-A0AY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

PHKG2

SNV

Missense_Mutation

c.455G>A

p.Arg152Gln

p.R152Q

P15735

protein_coding

deleterious(0.01)

probably_damaging(0.991)

TCGA-C5-A1BK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

PHKG2

SNV

Missense_Mutation

rs532137455

c.1031N>A

p.Arg344Gln

p.R344Q

P15735

protein_coding

deleterious(0.01)

benign(0.371)

TCGA-AA-3864-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

PHKG2

SNV

Missense_Mutation

rs756052327

c.211N>T

p.Arg71Trp

p.R71W

P15735

protein_coding

deleterious(0.02)

probably_damaging(0.993)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

PHKG2

SNV

Missense_Mutation

c.455N>A

p.Arg152Gln

p.R152Q

P15735

protein_coding

deleterious(0.01)

probably_damaging(0.991)

TCGA-AZ-4315-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

PHKG2

SNV

Missense_Mutation

rs373732367

c.116N>A

p.Arg39His

p.R39H

P15735

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-G4-6320-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Chemotherapy

oxaliplatin

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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
5261	PHKG2	DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE, KINASE		SP-600125	SP-600125
5261	PHKG2	DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE, KINASE		ALSTERPAULLONE	ALSTERPAULLONE
5261	PHKG2	DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE, KINASE		GEFITINIB	GEFITINIB
5261	PHKG2	DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE, KINASE	inhibitor	135652717	STAUROSPORINE
5261	PHKG2	DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE, KINASE		TAE-684	TAE-684
5261	PHKG2	DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE, KINASE		GW441756X	GW441756X
5261	PHKG2	DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE, KINASE		RG-1530	RG-1530
5261	PHKG2	DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE, KINASE	inhibitor	249565818
5261	PHKG2	DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE, KINASE	inhibitor	HESPERADIN	HESPERADIN	19035792
5261	PHKG2	DRUGGABLE GENOME, ENZYME, SERINE THREONINE KINASE, KINASE		OSI-632	OSI-632

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