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: UGGT2

Gene summary for UGGT2

Gene summary.

Gene information	Species	Human
	Gene symbol	UGGT2
	Gene ID	55757
	Gene name	UDP-glucose glycoprotein glucosyltransferase 2
	Gene Alias	HUGT2
	Cytomap	13q32.1
	Gene Type	protein-coding
	GO ID	GO:0006011
	UniProtAcc	Q05D90

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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
55757	UGGT2	CCI_1	Human	Cervix	CC	5.38e-03	5.53e-01	0.528
55757	UGGT2	CCI_2	Human	Cervix	CC	5.90e-05	7.11e-01	0.5249
55757	UGGT2	CCI_3	Human	Cervix	CC	1.08e-10	7.11e-01	0.516
55757	UGGT2	HTA11_3410_2000001011	Human	Colorectum	AD	2.51e-21	-6.73e-01	0.0155
55757	UGGT2	HTA11_2487_2000001011	Human	Colorectum	SER	3.22e-12	-6.66e-01	-0.1808
55757	UGGT2	HTA11_1938_2000001011	Human	Colorectum	AD	6.20e-04	-4.60e-01	-0.0811
55757	UGGT2	HTA11_3361_2000001011	Human	Colorectum	AD	1.20e-07	-5.72e-01	-0.1207
55757	UGGT2	HTA11_83_2000001011	Human	Colorectum	SER	1.22e-03	-5.35e-01	-0.1526
55757	UGGT2	HTA11_696_2000001011	Human	Colorectum	AD	1.11e-13	-5.27e-01	-0.1464
55757	UGGT2	HTA11_866_2000001011	Human	Colorectum	AD	4.82e-08	-4.36e-01	-0.1001
55757	UGGT2	HTA11_5212_2000001011	Human	Colorectum	AD	2.92e-04	-6.66e-01	-0.2061
55757	UGGT2	HTA11_546_2000001011	Human	Colorectum	AD	8.50e-06	-6.36e-01	-0.0842
55757	UGGT2	HTA11_7862_2000001011	Human	Colorectum	AD	4.48e-04	-5.76e-01	-0.0179
55757	UGGT2	HTA11_866_3004761011	Human	Colorectum	AD	2.37e-12	-5.88e-01	0.096
55757	UGGT2	HTA11_9408_2000001011	Human	Colorectum	AD	7.95e-04	-8.40e-01	0.0451
55757	UGGT2	HTA11_8622_2000001021	Human	Colorectum	SER	2.77e-02	-5.55e-01	0.0528
55757	UGGT2	HTA11_10711_2000001011	Human	Colorectum	AD	1.28e-05	-5.02e-01	0.0338
55757	UGGT2	HTA11_7696_3000711011	Human	Colorectum	AD	7.72e-11	-4.28e-01	0.0674
55757	UGGT2	HTA11_99999970781_79442	Human	Colorectum	MSS	4.33e-07	-4.22e-01	0.294
55757	UGGT2	HTA11_99999965104_69814	Human	Colorectum	MSS	4.86e-05	6.65e-01	0.281

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
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:001049810	Cervix	CC	proteasomal protein catabolic process	111/2311	490/18723	8.98e-11	1.58e-08	111
GO:003497610	Cervix	CC	response to endoplasmic reticulum stress	57/2311	256/18723	5.81e-06	1.42e-04	57
GO:003596610	Cervix	CC	response to topologically incorrect protein	39/2311	159/18723	1.68e-05	3.22e-04	39
GO:003596710	Cervix	CC	cellular response to topologically incorrect protein	29/2311	116/18723	1.35e-04	1.66e-03	29
GO:0010498	Colorectum	AD	proteasomal protein catabolic process	174/3918	490/18723	3.18e-14	7.66e-12	174
GO:0034976	Colorectum	AD	response to endoplasmic reticulum stress	90/3918	256/18723	8.48e-08	4.28e-06	90
GO:0018279	Colorectum	AD	protein N-linked glycosylation via asparagine	15/3918	23/18723	5.47e-06	1.40e-04	15
GO:0018196	Colorectum	AD	peptidyl-asparagine modification	15/3918	24/18723	1.18e-05	2.62e-04	15
GO:0035966	Colorectum	AD	response to topologically incorrect protein	54/3918	159/18723	8.85e-05	1.36e-03	54
GO:0035967	Colorectum	AD	cellular response to topologically incorrect protein	42/3918	116/18723	1.04e-04	1.56e-03	42
GO:0006515	Colorectum	AD	protein quality control for misfolded or incompletely synthesized proteins	14/3918	28/18723	6.01e-04	6.33e-03	14
GO:0006487	Colorectum	AD	protein N-linked glycosylation	25/3918	65/18723	9.12e-04	8.71e-03	25
GO:0009225	Colorectum	AD	nucleotide-sugar metabolic process	16/3918	36/18723	1.27e-03	1.12e-02	16
GO:0006486	Colorectum	AD	protein glycosylation	64/3918	226/18723	4.86e-03	3.27e-02	64
GO:0043413	Colorectum	AD	macromolecule glycosylation	64/3918	226/18723	4.86e-03	3.27e-02	64
GO:0071712	Colorectum	AD	ER-associated misfolded protein catabolic process	7/3918	12/18723	5.09e-03	3.38e-02	7
GO:0036503	Colorectum	AD	ERAD pathway	34/3918	107/18723	5.57e-03	3.63e-02	34
GO:0070085	Colorectum	AD	glycosylation	67/3918	240/18723	5.78e-03	3.67e-02	67
GO:00104981	Colorectum	SER	proteasomal protein catabolic process	132/2897	490/18723	3.08e-11	5.55e-09	132
GO:00349761	Colorectum	SER	response to endoplasmic reticulum stress	74/2897	256/18723	3.01e-08	2.05e-06	74

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0414120	Cervix	CC	Protein processing in endoplasmic reticulum	55/1267	174/8465	1.74e-08	2.68e-07	1.58e-07	55
hsa04141110	Cervix	CC	Protein processing in endoplasmic reticulum	55/1267	174/8465	1.74e-08	2.68e-07	1.58e-07	55
hsa04141	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa041411	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa041412	Colorectum	SER	Protein processing in endoplasmic reticulum	60/1580	174/8465	4.20e-07	7.33e-06	5.32e-06	60
hsa041413	Colorectum	SER	Protein processing in endoplasmic reticulum	60/1580	174/8465	4.20e-07	7.33e-06	5.32e-06	60
hsa041414	Colorectum	MSS	Protein processing in endoplasmic reticulum	75/1875	174/8465	3.78e-10	8.44e-09	5.17e-09	75
hsa041415	Colorectum	MSS	Protein processing in endoplasmic reticulum	75/1875	174/8465	3.78e-10	8.44e-09	5.17e-09	75
hsa041418	Colorectum	FAP	Protein processing in endoplasmic reticulum	50/1404	174/8465	3.64e-05	3.68e-04	2.24e-04	50
hsa041419	Colorectum	FAP	Protein processing in endoplasmic reticulum	50/1404	174/8465	3.64e-05	3.68e-04	2.24e-04	50
hsa0414126	Endometrium	AEH	Protein processing in endoplasmic reticulum	62/1197	174/8465	5.97e-13	1.39e-11	1.01e-11	62
hsa04141111	Endometrium	AEH	Protein processing in endoplasmic reticulum	62/1197	174/8465	5.97e-13	1.39e-11	1.01e-11	62
hsa0414127	Endometrium	EEC	Protein processing in endoplasmic reticulum	64/1237	174/8465	2.17e-13	5.09e-12	3.80e-12	64
hsa0414136	Endometrium	EEC	Protein processing in endoplasmic reticulum	64/1237	174/8465	2.17e-13	5.09e-12	3.80e-12	64
hsa04141211	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa04141310	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa0414122	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0414132	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0414123	Lung	AIS	Protein processing in endoplasmic reticulum	35/961	174/8465	4.88e-04	4.39e-03	2.81e-03	35
hsa0414133	Lung	AIS	Protein processing in endoplasmic reticulum	35/961	174/8465	4.88e-04	4.39e-03	2.81e-03	35

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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

UGGT2

SNV

Missense_Mutation

c.1064T>C

p.Met355Thr

p.M355T

Q9NYU1

protein_coding

deleterious(0)

possibly_damaging(0.521)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UGGT2

SNV

Missense_Mutation

c.4382N>C

p.Arg1461Thr

p.R1461T

Q9NYU1

protein_coding

tolerated(0.23)

benign(0.028)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UGGT2

SNV

Missense_Mutation

rs763999611

c.3946N>A

p.Leu1316Ile

p.L1316I

Q9NYU1

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UGGT2

SNV

Missense_Mutation

novel

c.2272N>A

p.Leu758Ile

p.L758I

Q9NYU1

protein_coding

tolerated(0.05)

benign(0.023)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UGGT2

SNV

Missense_Mutation

novel

c.4330N>T

p.Pro1444Ser

p.P1444S

Q9NYU1

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AR-A2LE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

UGGT2

SNV

Missense_Mutation

c.2320N>T

p.Gly774Trp

p.G774W

Q9NYU1

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-B6-A0WY-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

UGGT2

SNV

Missense_Mutation

novel

c.808N>A

p.Gly270Arg

p.G270R

Q9NYU1

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-BH-A0B8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

UGGT2

SNV

Missense_Mutation

c.1899N>A

p.Met633Ile

p.M633I

Q9NYU1

protein_coding

tolerated(0.15)

benign(0)

TCGA-BH-A0DZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

UGGT2

SNV

Missense_Mutation

c.3423G>C

p.Trp1141Cys

p.W1141C

Q9NYU1

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-BH-A18I-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

UGGT2

SNV

Missense_Mutation

c.3202N>C

p.Asp1068His

p.D1068H

Q9NYU1

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A18Q-01

Breast

breast invasive carcinoma

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
55757	UGGT2	NA		hydrochlorothiazide	HYDROCHLOROTHIAZIDE

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