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: URI1

Gene summary for URI1

Gene summary.

Gene information	Species	Human
	Gene symbol	URI1
	Gene ID	8725
	Gene name	URI1 prefoldin like chaperone
	Gene Alias	C19orf2
	Cytomap	19q12
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	O94763

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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
8725	URI1	P82T-E	Human	Esophagus	ESCC	1.18e-11	4.49e-01	0.1072
8725	URI1	P83T-E	Human	Esophagus	ESCC	3.39e-18	5.71e-01	0.1738
8725	URI1	P84T-E	Human	Esophagus	ESCC	2.90e-04	1.32e-01	0.0933
8725	URI1	P89T-E	Human	Esophagus	ESCC	3.34e-08	5.24e-01	0.1752
8725	URI1	P91T-E	Human	Esophagus	ESCC	9.96e-05	8.93e-01	0.1828
8725	URI1	P104T-E	Human	Esophagus	ESCC	4.27e-02	1.24e-01	0.0931
8725	URI1	P107T-E	Human	Esophagus	ESCC	9.21e-18	4.58e-01	0.171
8725	URI1	P126T-E	Human	Esophagus	ESCC	1.43e-03	8.80e-01	0.1125
8725	URI1	P127T-E	Human	Esophagus	ESCC	3.16e-21	3.88e-01	0.0826
8725	URI1	P128T-E	Human	Esophagus	ESCC	9.94e-22	8.23e-01	0.1241
8725	URI1	P130T-E	Human	Esophagus	ESCC	3.38e-46	1.01e+00	0.1676
8725	URI1	NAFLD1	Human	Liver	NAFLD	9.55e-06	5.59e-01	-0.04
8725	URI1	HCC1_Meng	Human	Liver	HCC	2.42e-77	2.94e-01	0.0246
8725	URI1	HCC2_Meng	Human	Liver	HCC	1.35e-30	2.44e-01	0.0107
8725	URI1	HCC1	Human	Liver	HCC	1.23e-02	3.52e+00	0.5336
8725	URI1	HCC2	Human	Liver	HCC	1.83e-15	4.40e+00	0.5341
8725	URI1	Pt13.b	Human	Liver	HCC	5.99e-05	8.90e-02	0.0251
8725	URI1	S014	Human	Liver	HCC	9.03e-03	3.39e-01	0.2254
8725	URI1	S015	Human	Liver	HCC	8.32e-09	5.69e-01	0.2375
8725	URI1	S016	Human	Liver	HCC	1.26e-02	3.50e-01	0.2243

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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
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
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:009719310	Cervix	CC	intrinsic apoptotic signaling pathway	85/2311	288/18723	4.56e-15	6.46e-12	85
GO:200123310	Cervix	CC	regulation of apoptotic signaling pathway	96/2311	356/18723	4.08e-14	3.05e-11	96
GO:200124210	Cervix	CC	regulation of intrinsic apoptotic signaling pathway	52/2311	164/18723	5.06e-11	1.01e-08	52
GO:200123410	Cervix	CC	negative regulation of apoptotic signaling pathway	56/2311	224/18723	1.39e-07	6.70e-06	56
GO:00513469	Cervix	CC	negative regulation of hydrolase activity	81/2311	379/18723	4.27e-07	1.67e-05	81
GO:004854510	Cervix	CC	response to steroid hormone	74/2311	339/18723	5.71e-07	2.09e-05	74
GO:004593610	Cervix	CC	negative regulation of phosphate metabolic process	88/2311	441/18723	2.92e-06	8.27e-05	88
GO:001056310	Cervix	CC	negative regulation of phosphorus metabolic process	88/2311	442/18723	3.21e-06	8.77e-05	88
GO:00160498	Cervix	CC	cell growth	92/2311	482/18723	1.16e-05	2.49e-04	92
GO:200124310	Cervix	CC	negative regulation of intrinsic apoptotic signaling pathway	28/2311	98/18723	1.31e-05	2.66e-04	28
GO:00096158	Cervix	CC	response to virus	73/2311	367/18723	2.22e-05	3.95e-04	73
GO:00015588	Cervix	CC	regulation of cell growth	77/2311	414/18723	1.40e-04	1.70e-03	77
GO:003530310	Cervix	CC	regulation of dephosphorylation	31/2311	128/18723	1.52e-04	1.83e-03	31
GO:00109218	Cervix	CC	regulation of phosphatase activity	22/2311	84/18723	4.18e-04	4.23e-03	22
GO:00163117	Cervix	CC	dephosphorylation	73/2311	417/18723	1.23e-03	9.87e-03	73
GO:00713839	Cervix	CC	cellular response to steroid hormone stimulus	40/2311	204/18723	1.93e-03	1.42e-02	40
GO:0097193	Colorectum	AD	intrinsic apoptotic signaling pathway	108/3918	288/18723	6.25e-11	6.41e-09	108
GO:2001242	Colorectum	AD	regulation of intrinsic apoptotic signaling pathway	67/3918	164/18723	4.94e-09	3.16e-07	67
GO:2001233	Colorectum	AD	regulation of apoptotic signaling pathway	119/3918	356/18723	2.14e-08	1.21e-06	119
GO:0071383	Colorectum	AD	cellular response to steroid hormone stimulus	73/3918	204/18723	6.31e-07	2.24e-05	73

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

URI1

SNV

Missense_Mutation

novel

c.508N>A

p.Glu170Lys

p.E170K

O94763

protein_coding

tolerated(0.13)

benign(0.099)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

URI1

SNV

Missense_Mutation

c.1546N>A

p.Ser516Thr

p.S516T

O94763

protein_coding

tolerated(0.15)

benign(0.156)

TCGA-AN-A0XU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

URI1

SNV

Missense_Mutation

c.828A>T

p.Glu276Asp

p.E276D

O94763

protein_coding

tolerated_low_confidence(0.24)

benign(0)

TCGA-AO-A03R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

URI1

deletion

Frame_Shift_Del

novel

c.1607delN

p.Ter536TrpfsTer14

p.*536Wfs*14

O94763

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

URI1

SNV

Missense_Mutation

novel

c.1516C>A

p.Pro506Thr

p.P506T

O94763

protein_coding

deleterious_low_confidence(0.03)

possibly_damaging(0.674)

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

URI1

SNV

Missense_Mutation

rs769475335

c.638G>A

p.Arg213Gln

p.R213Q

O94763

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

URI1

SNV

Missense_Mutation

novel

c.878C>A

p.Ser293Tyr

p.S293Y

O94763

protein_coding

deleterious(0)

possibly_damaging(0.483)

TCGA-VS-A9UR-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

URI1

SNV

Missense_Mutation

rs138648155

c.770N>T

p.Ala257Val

p.A257V

O94763

protein_coding

tolerated(0.64)

benign(0)

TCGA-AA-3821-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

URI1

SNV

Missense_Mutation

c.747N>T

p.Glu249Asp

p.E249D

O94763

protein_coding

tolerated(0.11)

probably_damaging(0.978)

TCGA-AD-6899-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Unknown

URI1

SNV

Missense_Mutation

novel

c.287N>C

p.Val96Ala

p.V96A

O94763

protein_coding

deleterious(0)

probably_damaging(0.913)

TCGA-AZ-4315-01

Colorectum

colon adenocarcinoma

Male

<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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