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: UBXN1

Gene summary for UBXN1

Gene summary.

Gene information	Species	Human
	Gene symbol	UBXN1
	Gene ID	51035
	Gene name	UBX domain protein 1
	Gene Alias	2B28
	Cytomap	11q12.3
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	A0A024R598

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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
51035	UBXN1	GSM4909281	Human	Breast	IDC	4.51e-10	-3.26e-01	0.21
51035	UBXN1	GSM4909282	Human	Breast	IDC	3.78e-12	-3.91e-01	-0.0288
51035	UBXN1	GSM4909286	Human	Breast	IDC	4.09e-15	-2.57e-01	0.1081
51035	UBXN1	GSM4909287	Human	Breast	IDC	4.30e-09	-3.90e-01	0.2057
51035	UBXN1	GSM4909290	Human	Breast	IDC	2.95e-02	-3.07e-01	0.2096
51035	UBXN1	GSM4909293	Human	Breast	IDC	7.94e-08	-3.30e-01	0.1581
51035	UBXN1	GSM4909294	Human	Breast	IDC	7.91e-17	-3.64e-01	0.2022
51035	UBXN1	GSM4909296	Human	Breast	IDC	1.46e-17	-2.14e-01	0.1524
51035	UBXN1	GSM4909297	Human	Breast	IDC	1.07e-26	-3.44e-01	0.1517
51035	UBXN1	GSM4909298	Human	Breast	IDC	9.19e-05	-2.32e-01	0.1551
51035	UBXN1	GSM4909302	Human	Breast	IDC	4.67e-05	-2.79e-01	0.1545
51035	UBXN1	GSM4909304	Human	Breast	IDC	2.29e-10	-3.62e-01	0.1636
51035	UBXN1	GSM4909309	Human	Breast	IDC	4.94e-03	2.23e-02	0.0483
51035	UBXN1	GSM4909311	Human	Breast	IDC	2.41e-46	-3.74e-01	0.1534
51035	UBXN1	GSM4909312	Human	Breast	IDC	3.39e-17	-2.04e-01	0.1552
51035	UBXN1	GSM4909315	Human	Breast	IDC	5.32e-14	-4.72e-01	0.21
51035	UBXN1	GSM4909316	Human	Breast	IDC	7.03e-06	-5.36e-01	0.21
51035	UBXN1	GSM4909319	Human	Breast	IDC	5.73e-59	-5.16e-01	0.1563
51035	UBXN1	GSM4909320	Human	Breast	IDC	6.50e-07	-3.36e-01	0.1575
51035	UBXN1	GSM4909321	Human	Breast	IDC	8.85e-18	9.16e-04	0.1559

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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
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:200005910	Cervix	CC	negative regulation of ubiquitin-dependent protein catabolic process	16/2311	48/18723	1.27e-04	1.58e-03	16
GO:00324356	Cervix	CC	negative regulation of proteasomal ubiquitin-dependent protein catabolic process	11/2311	35/18723	2.43e-03	1.71e-02	11
GO:19017995	Cervix	CC	negative regulation of proteasomal protein catabolic process	13/2311	49/18723	5.34e-03	3.10e-02	13
GO:00711083	Cervix	CC	protein K48-linked deubiquitination	10/2311	35/18723	7.99e-03	4.18e-02	10
GO:0042176	Colorectum	AD	regulation of protein catabolic process	160/3918	391/18723	1.06e-19	7.34e-17	160
GO:1903362	Colorectum	AD	regulation of cellular protein catabolic process	109/3918	255/18723	2.14e-15	6.08e-13	109
GO:0010498	Colorectum	AD	proteasomal protein catabolic process	174/3918	490/18723	3.18e-14	7.66e-12	174
GO:0009895	Colorectum	AD	negative regulation of catabolic process	124/3918	320/18723	1.66e-13	3.35e-11	124
GO:1903050	Colorectum	AD	regulation of proteolysis involved in cellular protein catabolic process	92/3918	221/18723	2.04e-12	3.19e-10	92
GO:0031330	Colorectum	AD	negative regulation of cellular catabolic process	104/3918	262/18723	2.66e-12	3.96e-10	104
GO:0043161	Colorectum	AD	proteasome-mediated ubiquitin-dependent protein catabolic process	141/3918	412/18723	1.77e-10	1.68e-08	141
GO:0042177	Colorectum	AD	negative regulation of protein catabolic process	55/3918	121/18723	1.19e-09	8.85e-08	55
GO:0061136	Colorectum	AD	regulation of proteasomal protein catabolic process	75/3918	187/18723	1.65e-09	1.20e-07	75
GO:2000058	Colorectum	AD	regulation of ubiquitin-dependent protein catabolic process	68/3918	164/18723	1.82e-09	1.31e-07	68
GO:1903363	Colorectum	AD	negative regulation of cellular protein catabolic process	39/3918	75/18723	2.69e-09	1.87e-07	39
GO:0034976	Colorectum	AD	response to endoplasmic reticulum stress	90/3918	256/18723	8.48e-08	4.28e-06	90
GO:1903320	Colorectum	AD	regulation of protein modification by small protein conjugation or removal	86/3918	242/18723	9.43e-08	4.65e-06	86
GO:0032434	Colorectum	AD	regulation of proteasomal ubiquitin-dependent protein catabolic process	54/3918	134/18723	2.51e-07	1.02e-05	54
GO:1903051	Colorectum	AD	negative regulation of proteolysis involved in cellular protein catabolic process	31/3918	64/18723	8.71e-07	2.98e-05	31
GO:0052547	Colorectum	AD	regulation of peptidase activity	137/3918	461/18723	4.12e-06	1.12e-04	137

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0414124	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36
hsa0414134	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36
hsa0414143	Breast	DCIS	Protein processing in endoplasmic reticulum	36/846	174/8465	1.60e-05	1.91e-04	1.41e-04	36
hsa0414153	Breast	DCIS	Protein processing in endoplasmic reticulum	36/846	174/8465	1.60e-05	1.91e-04	1.41e-04	36
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
hsa041416	Colorectum	MSI-H	Protein processing in endoplasmic reticulum	46/797	174/8465	4.53e-11	9.78e-10	8.19e-10	46
hsa041417	Colorectum	MSI-H	Protein processing in endoplasmic reticulum	46/797	174/8465	4.53e-11	9.78e-10	8.19e-10	46
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

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
UBXN1	PLA	Lung	Healthy	STK17B,RIPK3,SELK, etc.	7.36e-02

∗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

UBXN1

SNV

Missense_Mutation

c.7G>A

p.Glu3Lys

p.E3K

Q04323

protein_coding

deleterious(0.01)

probably_damaging(0.946)

TCGA-AC-A2B8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

chemo

UBXN1

SNV

Missense_Mutation

rs752020123

c.370N>G

p.Arg124Gly

p.R124G

Q04323

protein_coding

deleterious(0.02)

probably_damaging(0.998)

TCGA-D8-A1Y1-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

UBXN1

SNV

Missense_Mutation

rs752020123

c.370N>G

p.Arg124Gly

p.R124G

Q04323

protein_coding

deleterious(0.02)

probably_damaging(0.998)

TCGA-E9-A22A-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

UBXN1

SNV

Missense_Mutation

c.904N>A

p.Gly302Arg

p.G302R

Q04323

protein_coding

tolerated_low_confidence(0.92)

benign(0.003)

TCGA-DG-A2KM-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

UBXN1

SNV

Missense_Mutation

novel

c.355N>A

p.Glu119Lys

p.E119K

Q04323

protein_coding

deleterious(0.01)

probably_damaging(0.994)

TCGA-DG-A2KM-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

UBXN1

SNV

Missense_Mutation

rs546476489

c.740G>A

p.Arg247His

p.R247H

Q04323

protein_coding

deleterious(0.02)

benign(0.228)

TCGA-G4-6628-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

UBXN1

SNV

Missense_Mutation

novel

c.781C>A

p.Leu261Ile

p.L261I

Q04323

protein_coding

tolerated(0.17)

benign(0.022)

TCGA-EI-6917-01

Colorectum

rectum adenocarcinoma

Male

<65

III/IV

Chemotherapy

5fluorouracil+oxaciplatina+l-folinian

UBXN1

deletion

Frame_Shift_Del

c.461delN

p.Lys154ArgfsTer5

p.K154Rfs*5

Q04323

protein_coding

TCGA-WS-AB45-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

UBXN1

SNV

Missense_Mutation

novel

c.343N>T

p.Arg115Trp

p.R115W

Q04323

protein_coding

deleterious(0.01)

probably_damaging(0.978)

TCGA-AJ-A8CT-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

UBXN1

SNV

Missense_Mutation

novel

c.197N>A

p.Ser66Tyr

p.S66Y

Q04323

protein_coding

deleterious(0.03)

benign(0)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid 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

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