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: GUSB

Gene summary for GUSB

Gene summary.

Gene information	Species	Human
	Gene symbol	GUSB
	Gene ID	2990
	Gene name	glucuronidase beta
	Gene Alias	BG
	Cytomap	7q11.21
	Gene Type	protein-coding
	GO ID	GO:0005975
	UniProtAcc	P08236

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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
2990	GUSB	LZE4T	Human	Esophagus	ESCC	1.02e-05	5.06e-02	0.0811
2990	GUSB	LZE7T	Human	Esophagus	ESCC	9.69e-09	5.23e-01	0.0667
2990	GUSB	LZE8T	Human	Esophagus	ESCC	2.88e-07	1.86e-01	0.067
2990	GUSB	LZE24T	Human	Esophagus	ESCC	1.01e-15	4.15e-01	0.0596
2990	GUSB	LZE6T	Human	Esophagus	ESCC	1.16e-05	2.12e-01	0.0845
2990	GUSB	P1T-E	Human	Esophagus	ESCC	1.08e-14	6.94e-01	0.0875
2990	GUSB	P2T-E	Human	Esophagus	ESCC	3.20e-21	4.13e-01	0.1177
2990	GUSB	P4T-E	Human	Esophagus	ESCC	8.51e-20	4.48e-01	0.1323
2990	GUSB	P5T-E	Human	Esophagus	ESCC	9.48e-15	9.23e-02	0.1327
2990	GUSB	P8T-E	Human	Esophagus	ESCC	2.18e-28	3.56e-01	0.0889
2990	GUSB	P9T-E	Human	Esophagus	ESCC	3.08e-15	3.08e-01	0.1131
2990	GUSB	P10T-E	Human	Esophagus	ESCC	2.10e-36	6.21e-01	0.116
2990	GUSB	P11T-E	Human	Esophagus	ESCC	1.44e-11	6.07e-01	0.1426
2990	GUSB	P12T-E	Human	Esophagus	ESCC	4.28e-57	1.01e+00	0.1122
2990	GUSB	P15T-E	Human	Esophagus	ESCC	5.58e-24	6.62e-01	0.1149
2990	GUSB	P16T-E	Human	Esophagus	ESCC	6.45e-49	9.71e-01	0.1153
2990	GUSB	P17T-E	Human	Esophagus	ESCC	3.59e-05	3.21e-01	0.1278
2990	GUSB	P19T-E	Human	Esophagus	ESCC	4.47e-05	4.82e-01	0.1662
2990	GUSB	P20T-E	Human	Esophagus	ESCC	1.94e-14	1.94e-01	0.1124
2990	GUSB	P21T-E	Human	Esophagus	ESCC	2.20e-35	7.22e-01	0.1617

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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
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:00442626	Esophagus	ESCC	cellular carbohydrate metabolic process	160/8552	283/18723	1.43e-04	9.66e-04	160
GO:19016574	Esophagus	ESCC	glycosyl compound metabolic process	57/8552	88/18723	2.32e-04	1.44e-03	57
GO:001605216	Esophagus	ESCC	carbohydrate catabolic process	91/8552	154/18723	5.39e-04	2.97e-03	91
GO:19011362	Esophagus	ESCC	carbohydrate derivative catabolic process	99/8552	172/18723	1.11e-03	5.54e-03	99
GO:00442751	Esophagus	ESCC	cellular carbohydrate catabolic process	27/8552	40/18723	4.39e-03	1.73e-02	27
GO:00161373	Esophagus	ESCC	glycoside metabolic process	16/8552	22/18723	9.46e-03	3.28e-02	16
GO:001605212	Liver	Cirrhotic	carbohydrate catabolic process	66/4634	154/18723	6.10e-07	1.32e-05	66
GO:004426211	Liver	Cirrhotic	cellular carbohydrate metabolic process	97/4634	283/18723	1.89e-04	1.76e-03	97
GO:19016572	Liver	Cirrhotic	glycosyl compound metabolic process	37/4634	88/18723	2.70e-04	2.40e-03	37
GO:0016137	Liver	Cirrhotic	glycoside metabolic process	11/4634	22/18723	9.18e-03	4.21e-02	11
GO:001605222	Liver	HCC	carbohydrate catabolic process	99/7958	154/18723	3.79e-08	8.30e-07	99
GO:004426221	Liver	HCC	cellular carbohydrate metabolic process	153/7958	283/18723	5.27e-05	5.00e-04	153
GO:1901136	Liver	HCC	carbohydrate derivative catabolic process	98/7958	172/18723	8.71e-05	7.62e-04	98
GO:19016571	Liver	HCC	glycosyl compound metabolic process	55/7958	88/18723	1.20e-04	1.01e-03	55
GO:00161371	Liver	HCC	glycoside metabolic process	16/7958	22/18723	4.03e-03	1.76e-02	16
GO:19016573	Oral cavity	OSCC	glycosyl compound metabolic process	52/7305	88/18723	1.06e-04	7.84e-04	52
GO:19011361	Oral cavity	OSCC	carbohydrate derivative catabolic process	89/7305	172/18723	4.52e-04	2.73e-03	89
GO:001605210	Oral cavity	OSCC	carbohydrate catabolic process	76/7305	154/18723	5.67e-03	2.18e-02	76
GO:00442625	Oral cavity	OSCC	cellular carbohydrate metabolic process	130/7305	283/18723	9.98e-03	3.49e-02	130
GO:190165711	Oral cavity	LP	glycosyl compound metabolic process	43/4623	88/18723	7.80e-07	2.05e-05	43

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0414222	Esophagus	ESCC	Lysosome	102/4205	132/8465	5.11e-11	7.13e-10	3.65e-10	102
hsa012405	Esophagus	ESCC	Biosynthesis of cofactors	97/4205	153/8465	3.88e-04	1.35e-03	6.94e-04	97
hsa0414232	Esophagus	ESCC	Lysosome	102/4205	132/8465	5.11e-11	7.13e-10	3.65e-10	102
hsa0124012	Esophagus	ESCC	Biosynthesis of cofactors	97/4205	153/8465	3.88e-04	1.35e-03	6.94e-04	97
hsa041424	Liver	Cirrhotic	Lysosome	68/2530	132/8465	1.34e-07	1.97e-06	1.21e-06	68
hsa01240	Liver	Cirrhotic	Biosynthesis of cofactors	66/2530	153/8465	3.11e-04	1.99e-03	1.23e-03	66
hsa00983	Liver	Cirrhotic	Drug metabolism - other enzymes	34/2530	80/8465	1.08e-02	3.57e-02	2.20e-02	34
hsa0414211	Liver	Cirrhotic	Lysosome	68/2530	132/8465	1.34e-07	1.97e-06	1.21e-06	68
hsa012401	Liver	Cirrhotic	Biosynthesis of cofactors	66/2530	153/8465	3.11e-04	1.99e-03	1.23e-03	66
hsa009831	Liver	Cirrhotic	Drug metabolism - other enzymes	34/2530	80/8465	1.08e-02	3.57e-02	2.20e-02	34
hsa041422	Liver	HCC	Lysosome	100/4020	132/8465	2.32e-11	4.31e-10	2.40e-10	100
hsa012402	Liver	HCC	Biosynthesis of cofactors	103/4020	153/8465	4.67e-07	5.05e-06	2.81e-06	103
hsa009832	Liver	HCC	Drug metabolism - other enzymes	54/4020	80/8465	2.25e-04	1.09e-03	6.08e-04	54
hsa041423	Liver	HCC	Lysosome	100/4020	132/8465	2.32e-11	4.31e-10	2.40e-10	100
hsa012403	Liver	HCC	Biosynthesis of cofactors	103/4020	153/8465	4.67e-07	5.05e-06	2.81e-06	103
hsa009833	Liver	HCC	Drug metabolism - other enzymes	54/4020	80/8465	2.25e-04	1.09e-03	6.08e-04	54
hsa041425	Oral cavity	OSCC	Lysosome	87/3704	132/8465	1.97e-07	1.35e-06	6.86e-07	87
hsa012404	Oral cavity	OSCC	Biosynthesis of cofactors	88/3704	153/8465	3.84e-04	1.20e-03	6.12e-04	88
hsa0414212	Oral cavity	OSCC	Lysosome	87/3704	132/8465	1.97e-07	1.35e-06	6.86e-07	87
hsa0124011	Oral cavity	OSCC	Biosynthesis of cofactors	88/3704	153/8465	3.84e-04	1.20e-03	6.12e-04	88

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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

GUSB

SNV

Missense_Mutation

rs759010501

c.1163N>G

p.Tyr388Cys

p.Y388C

P08236

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A8-A09I-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

GUSB

SNV

Missense_Mutation

c.627N>G

p.Phe209Leu

p.F209L

P08236

protein_coding

deleterious(0.02)

possibly_damaging(0.797)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GUSB

SNV

Missense_Mutation

c.1070N>A

p.Arg357Gln

p.R357Q

P08236

protein_coding

deleterious(0)

possibly_damaging(0.626)

TCGA-D8-A1XY-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

tamoxiphen

GUSB

SNV

Missense_Mutation

c.286N>A

p.Val96Ile

p.V96I

P08236

protein_coding

tolerated(0.59)

benign(0.007)

TCGA-D8-A27T-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicine+cyclophosphamide

GUSB

SNV

Missense_Mutation

c.959A>G

p.Tyr320Cys

p.Y320C

P08236

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-OL-A5RX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

GUSB

insertion

Nonsense_Mutation

novel

c.1565_1566insTCCTCCAGCCTGACCTGCGCCCA

p.Thr523ProfsTer4

p.T523Pfs*4

P08236

protein_coding

TCGA-A8-A07J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

GUSB

SNV

Missense_Mutation

rs771629102

c.1091N>T

p.Pro364Leu

p.P364L

P08236

protein_coding

deleterious(0.02)

benign(0.028)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

GUSB

SNV

Missense_Mutation

c.1190N>G

p.Asp397Gly

p.D397G

P08236

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-EK-A2R8-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

GUSB

SNV

Missense_Mutation

c.1054N>A

p.Glu352Lys

p.E352K

P08236

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

GUSB

SNV

Missense_Mutation

novel

c.178G>C

p.Glu60Gln

p.E60Q

P08236

protein_coding

tolerated(0.22)

benign(0.124)

TCGA-VS-A9U7-01

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
2990	GUSB	DRUGGABLE GENOME, ENZYME		PerioPatch
2990	GUSB	DRUGGABLE GENOME, ENZYME		Vestronidase alfa

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