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: UBXN2A

Gene summary for UBXN2A

Gene summary.

Gene information	Species	Human
	Gene symbol	UBXN2A
	Gene ID	165324
	Gene name	UBX domain protein 2A
	Gene Alias	UBXD4
	Cytomap	2p23.3
	Gene Type	protein-coding
	GO ID	GO:0000045
	UniProtAcc	P68543

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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
165324	UBXN2A	CCI_1	Human	Cervix	CC	5.24e-04	8.87e-01	0.528
165324	UBXN2A	CCI_2	Human	Cervix	CC	8.74e-03	5.26e-01	0.5249
165324	UBXN2A	LZE2T	Human	Esophagus	ESCC	6.08e-03	4.96e-01	0.082
165324	UBXN2A	LZE4T	Human	Esophagus	ESCC	3.22e-22	5.79e-01	0.0811
165324	UBXN2A	LZE7T	Human	Esophagus	ESCC	2.28e-10	4.26e-01	0.0667
165324	UBXN2A	LZE8T	Human	Esophagus	ESCC	1.06e-06	3.01e-01	0.067
165324	UBXN2A	LZE20T	Human	Esophagus	ESCC	9.74e-05	1.64e-01	0.0662
165324	UBXN2A	LZE21D1	Human	Esophagus	HGIN	3.57e-02	3.60e-01	0.0632
165324	UBXN2A	LZE22D1	Human	Esophagus	HGIN	3.15e-03	1.35e-01	0.0595
165324	UBXN2A	LZE24T	Human	Esophagus	ESCC	1.23e-18	4.74e-01	0.0596
165324	UBXN2A	LZE21T	Human	Esophagus	ESCC	1.99e-09	5.19e-01	0.0655
165324	UBXN2A	LZE6T	Human	Esophagus	ESCC	3.24e-02	9.00e-02	0.0845
165324	UBXN2A	P1T-E	Human	Esophagus	ESCC	3.76e-22	6.84e-01	0.0875
165324	UBXN2A	P2T-E	Human	Esophagus	ESCC	1.95e-69	1.09e+00	0.1177
165324	UBXN2A	P4T-E	Human	Esophagus	ESCC	1.71e-30	6.11e-01	0.1323
165324	UBXN2A	P5T-E	Human	Esophagus	ESCC	1.74e-24	4.27e-01	0.1327
165324	UBXN2A	P8T-E	Human	Esophagus	ESCC	2.67e-28	4.06e-01	0.0889
165324	UBXN2A	P9T-E	Human	Esophagus	ESCC	1.43e-26	4.92e-01	0.1131
165324	UBXN2A	P10T-E	Human	Esophagus	ESCC	1.17e-29	3.93e-01	0.116
165324	UBXN2A	P11T-E	Human	Esophagus	ESCC	9.25e-27	9.26e-01	0.1426

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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
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
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:004217610	Cervix	CC	regulation of protein catabolic process	104/2311	391/18723	9.39e-15	9.36e-12	104
GO:001049810	Cervix	CC	proteasomal protein catabolic process	111/2311	490/18723	8.98e-11	1.58e-08	111
GO:190332010	Cervix	CC	regulation of protein modification by small protein conjugation or removal	66/2311	242/18723	2.31e-10	3.46e-08	66
GO:003139610	Cervix	CC	regulation of protein ubiquitination	59/2311	210/18723	5.90e-10	7.51e-08	59
GO:004316110	Cervix	CC	proteasome-mediated ubiquitin-dependent protein catabolic process	91/2311	412/18723	1.65e-08	1.25e-06	91
GO:00162367	Cervix	CC	macroautophagy	58/2311	291/18723	1.40e-04	1.70e-03	58
GO:19908234	Cervix	CC	response to leukemia inhibitory factor	22/2311	95/18723	2.40e-03	1.70e-02	22
GO:00070304	Cervix	CC	Golgi organization	32/2311	157/18723	2.78e-03	1.87e-02	32
GO:19908304	Cervix	CC	cellular response to leukemia inhibitory factor	21/2311	94/18723	4.68e-03	2.82e-02	21
GO:00000452	Cervix	CC	autophagosome assembly	21/2311	99/18723	8.67e-03	4.46e-02	21
GO:004217627	Esophagus	HGIN	regulation of protein catabolic process	119/2587	391/18723	8.09e-18	2.43e-15	119
GO:001049826	Esophagus	HGIN	proteasomal protein catabolic process	139/2587	490/18723	1.20e-17	3.41e-15	139
GO:004316126	Esophagus	HGIN	proteasome-mediated ubiquitin-dependent protein catabolic process	114/2587	412/18723	7.00e-14	1.20e-11	114
GO:190332027	Esophagus	HGIN	regulation of protein modification by small protein conjugation or removal	78/2587	242/18723	1.40e-13	2.26e-11	78
GO:003139627	Esophagus	HGIN	regulation of protein ubiquitination	64/2587	210/18723	3.02e-10	2.71e-08	64
GO:001623616	Esophagus	HGIN	macroautophagy	77/2587	291/18723	7.15e-09	4.61e-07	77
GO:00070336	Esophagus	HGIN	vacuole organization	44/2587	180/18723	8.97e-05	1.96e-03	44
GO:00069975	Esophagus	HGIN	nucleus organization	34/2587	133/18723	2.20e-04	4.00e-03	34
GO:19050375	Esophagus	HGIN	autophagosome organization	28/2587	103/18723	2.58e-04	4.53e-03	28
GO:00000455	Esophagus	HGIN	autophagosome assembly	26/2587	99/18723	7.45e-04	9.90e-03	26

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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
hsa0414139	Esophagus	HGIN	Protein processing in endoplasmic reticulum	67/1383	174/8465	1.06e-12	2.16e-11	1.72e-11	67
hsa04141114	Esophagus	HGIN	Protein processing in endoplasmic reticulum	67/1383	174/8465	1.06e-12	2.16e-11	1.72e-11	67
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
hsa0414114	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114
hsa0414115	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114
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
hsa0414130	Oral cavity	OSCC	Protein processing in endoplasmic reticulum	143/3704	174/8465	6.82e-26	2.28e-23	1.16e-23	143
hsa04141113	Oral cavity	OSCC	Protein processing in endoplasmic reticulum	143/3704	174/8465	6.82e-26	2.28e-23	1.16e-23	143
hsa0414145	Oral cavity	EOLP	Protein processing in endoplasmic reticulum	70/1218	174/8465	2.84e-17	3.06e-15	1.81e-15	70
hsa0414155	Oral cavity	EOLP	Protein processing in endoplasmic reticulum	70/1218	174/8465	2.84e-17	3.06e-15	1.81e-15	70
hsa0414162	Oral cavity	NEOLP	Protein processing in endoplasmic reticulum	49/1112	174/8465	9.02e-08	1.37e-06	8.59e-07	49
hsa0414172	Oral cavity	NEOLP	Protein processing in endoplasmic reticulum	49/1112	174/8465	9.02e-08	1.37e-06	8.59e-07	49

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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

UBXN2A

SNV

Missense_Mutation

novel

c.34N>A

p.Glu12Lys

p.E12K

P68543

protein_coding

tolerated(0.22)

benign(0.001)

TCGA-5L-AAT0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

UBXN2A

SNV

Missense_Mutation

novel

c.301N>A

p.Glu101Lys

p.E101K

P68543

protein_coding

deleterious(0.01)

probably_damaging(0.952)

TCGA-A2-A0CR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

UBXN2A

SNV

Missense_Mutation

c.83A>G

p.Asn28Ser

p.N28S

P68543

protein_coding

tolerated(0.82)

benign(0)

TCGA-AR-A250-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

UBXN2A

insertion

In_Frame_Ins

novel

c.557_558insATCCTCCTGCCTCAGCCCCTCTAGTAGCTGGGA

p.Ile186_Val187insSerSerCysLeuSerProSerSerSerTrpAsp

p.I186_V187insSSCLSPSSSWD

P68543

protein_coding

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

UBXN2A

deletion

Frame_Shift_Del

c.209delA

p.Asn70ThrfsTer21

p.N70Tfs*21

P68543

protein_coding

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UBXN2A

SNV

Missense_Mutation

rs753336862

c.703N>A

p.Glu235Lys

p.E235K

P68543

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-VS-A8EL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

UBXN2A

SNV

Missense_Mutation

rs13386425

c.220G>A

p.Val74Ile

p.V74I

P68543

protein_coding

tolerated(0.09)

possibly_damaging(0.66)

TCGA-AA-3947-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

UBXN2A

SNV

Missense_Mutation

novel

c.626N>T

p.Ser209Phe

p.S209F

P68543

protein_coding

tolerated(0.18)

benign(0.024)

TCGA-AA-A02R-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

UBXN2A

insertion

Frame_Shift_Ins

rs780605417

c.742_743insA

p.Thr250AsnfsTer5

p.T250Nfs*5

P68543

protein_coding

TCGA-AA-3672-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

UBXN2A

SNV

Missense_Mutation

novel

c.512N>T

p.Glu171Val

p.E171V

P68543

protein_coding

deleterious(0.03)

possibly_damaging(0.867)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

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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