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: USP34

Gene summary for USP34

Gene summary.

Gene information	Species	Human
	Gene symbol	USP34
	Gene ID	9736
	Gene name	ubiquitin specific peptidase 34
	Gene Alias	USP34
	Cytomap	2p15
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	Q70CQ2

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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
9736	USP34	CA_HPV_1	Human	Cervix	CC	4.95e-02	-5.58e-02	0.0264
9736	USP34	CCI_1	Human	Cervix	CC	1.89e-03	1.36e+00	0.528
9736	USP34	CCI_2	Human	Cervix	CC	5.57e-12	1.59e+00	0.5249
9736	USP34	CCI_3	Human	Cervix	CC	6.87e-16	1.24e+00	0.516
9736	USP34	HTA11_3410_2000001011	Human	Colorectum	AD	6.89e-11	-5.44e-01	0.0155
9736	USP34	HTA11_2951_2000001011	Human	Colorectum	AD	1.35e-04	-7.23e-01	0.0216
9736	USP34	HTA11_347_2000001011	Human	Colorectum	AD	3.15e-03	3.33e-01	-0.1954
9736	USP34	HTA11_83_2000001011	Human	Colorectum	SER	1.13e-02	-2.69e-01	-0.1526
9736	USP34	HTA11_7862_2000001011	Human	Colorectum	AD	1.35e-03	-4.18e-01	-0.0179
9736	USP34	HTA11_866_3004761011	Human	Colorectum	AD	4.83e-11	-6.28e-01	0.096
9736	USP34	HTA11_8622_2000001021	Human	Colorectum	SER	3.19e-02	-6.28e-01	0.0528
9736	USP34	HTA11_10711_2000001011	Human	Colorectum	AD	1.14e-03	-4.33e-01	0.0338
9736	USP34	HTA11_7696_3000711011	Human	Colorectum	AD	3.87e-13	-5.25e-01	0.0674
9736	USP34	HTA11_7469_2000001011	Human	Colorectum	AD	5.74e-05	-7.54e-01	-0.0124
9736	USP34	HTA11_99999971662_82457	Human	Colorectum	MSS	1.05e-05	-3.26e-01	0.3859
9736	USP34	HTA11_99999973899_84307	Human	Colorectum	MSS	1.24e-03	-6.04e-01	0.2585
9736	USP34	HTA11_99999974143_84620	Human	Colorectum	MSS	7.26e-07	-4.02e-01	0.3005
9736	USP34	F007	Human	Colorectum	FAP	2.47e-04	-3.79e-01	0.1176
9736	USP34	A001-C-207	Human	Colorectum	FAP	5.76e-05	-1.82e-01	0.1278
9736	USP34	A015-C-203	Human	Colorectum	FAP	1.81e-36	-4.60e-01	-0.1294

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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
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:01987386	Lung	IAC	cell-cell signaling by wnt	95/2061	446/18723	1.46e-10	3.48e-08	95
GO:00301116	Lung	IAC	regulation of Wnt signaling pathway	74/2061	328/18723	1.14e-09	2.05e-07	74
GO:00608286	Lung	IAC	regulation of canonical Wnt signaling pathway	54/2061	253/18723	1.25e-06	6.46e-05	54
GO:00600706	Lung	IAC	canonical Wnt signaling pathway	61/2061	303/18723	2.09e-06	9.45e-05	61
GO:00301775	Lung	IAC	positive regulation of Wnt signaling pathway	32/2061	140/18723	4.34e-05	1.03e-03	32
GO:00902635	Lung	IAC	positive regulation of canonical Wnt signaling pathway	24/2061	106/18723	4.33e-04	6.43e-03	24
GO:001605512	Lung	AIS	Wnt signaling pathway	91/1849	444/18723	9.38e-12	5.47e-09	91
GO:019873812	Lung	AIS	cell-cell signaling by wnt	91/1849	446/18723	1.22e-11	6.13e-09	91
GO:003011112	Lung	AIS	regulation of Wnt signaling pathway	70/1849	328/18723	3.81e-10	8.87e-08	70
GO:006082812	Lung	AIS	regulation of canonical Wnt signaling pathway	52/1849	253/18723	2.40e-07	2.22e-05	52
GO:006007012	Lung	AIS	canonical Wnt signaling pathway	59/1849	303/18723	2.73e-07	2.37e-05	59
GO:003017712	Lung	AIS	positive regulation of Wnt signaling pathway	29/1849	140/18723	9.01e-05	2.21e-03	29
GO:009026312	Lung	AIS	positive regulation of canonical Wnt signaling pathway	22/1849	106/18723	5.91e-04	9.03e-03	22
GO:001605522	Lung	AAH	Wnt signaling pathway	28/613	444/18723	7.63e-04	2.63e-02	28
GO:019873822	Lung	AAH	cell-cell signaling by wnt	28/613	446/18723	8.18e-04	2.75e-02	28
GO:003011122	Lung	MIAC	regulation of Wnt signaling pathway	41/967	328/18723	1.51e-07	3.69e-05	41
GO:001605531	Lung	MIAC	Wnt signaling pathway	50/967	444/18723	1.88e-07	4.02e-05	50
GO:019873831	Lung	MIAC	cell-cell signaling by wnt	50/967	446/18723	2.16e-07	4.11e-05	50
GO:006082822	Lung	MIAC	regulation of canonical Wnt signaling pathway	28/967	253/18723	1.23e-04	5.10e-03	28
GO:006007022	Lung	MIAC	canonical Wnt signaling pathway	31/967	303/18723	2.31e-04	7.86e-03	31

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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

USP34

SNV

Missense_Mutation

novel

c.6466C>G

p.His2156Asp

p.H2156D

Q70CQ2

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

USP34

SNV

Missense_Mutation

c.4522N>G

p.Pro1508Ala

p.P1508A

Q70CQ2

protein_coding

tolerated(0.14)

benign(0.052)

TCGA-A7-A0DA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

USP34

SNV

Missense_Mutation

novel

c.4429N>A

p.Val1477Met

p.V1477M

Q70CQ2

protein_coding

tolerated(0.17)

benign(0)

TCGA-A7-A26I-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

USP34

SNV

Missense_Mutation

novel

c.6077N>G

p.Glu2026Gly

p.E2026G

Q70CQ2

protein_coding

deleterious(0)

probably_damaging(0.96)

TCGA-A7-A3RF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

USP34

SNV

Missense_Mutation

c.3980N>A

p.Pro1327Gln

p.P1327Q

Q70CQ2

protein_coding

deleterious(0)

probably_damaging(0.991)

TCGA-A8-A06X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

USP34

SNV

Missense_Mutation

c.9940N>G

p.Pro3314Ala

p.P3314A

Q70CQ2

protein_coding

tolerated(0.19)

benign(0.046)

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

USP34

SNV

Missense_Mutation

novel

c.6561N>A

p.Asn2187Lys

p.N2187K

Q70CQ2

protein_coding

deleterious(0)

probably_damaging(0.989)

TCGA-AC-A3YJ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

USP34

SNV

Missense_Mutation

novel

c.1503N>T

p.Lys501Asn

p.K501N

Q70CQ2

protein_coding

tolerated(0.07)

probably_damaging(0.966)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

USP34

SNV

Missense_Mutation

c.6764C>T

p.Ser2255Leu

p.S2255L

Q70CQ2

protein_coding

tolerated(0.09)

benign(0)

TCGA-AR-A0TX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

USP34

SNV

Missense_Mutation

c.4745N>T

p.Thr1582Ile

p.T1582I

Q70CQ2

protein_coding

deleterious(0.01)

probably_damaging(0.969)

TCGA-AR-A256-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

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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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