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: UBL4A

Gene summary for UBL4A

Gene summary.

Gene information	Species	Human
	Gene symbol	UBL4A
	Gene ID	8266
	Gene name	ubiquitin like 4A
	Gene Alias	DX254E
	Cytomap	Xq28
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	P11441

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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
8266	UBL4A	LZE4T	Human	Esophagus	ESCC	1.76e-05	1.47e-01	0.0811
8266	UBL4A	LZE7T	Human	Esophagus	ESCC	2.21e-07	4.11e-01	0.0667
8266	UBL4A	LZE20T	Human	Esophagus	ESCC	2.53e-03	1.21e-01	0.0662
8266	UBL4A	LZE22T	Human	Esophagus	ESCC	1.67e-04	3.24e-01	0.068
8266	UBL4A	LZE24T	Human	Esophagus	ESCC	4.31e-18	4.52e-01	0.0596
8266	UBL4A	LZE6T	Human	Esophagus	ESCC	3.91e-06	3.03e-01	0.0845
8266	UBL4A	P1T-E	Human	Esophagus	ESCC	1.53e-10	6.32e-01	0.0875
8266	UBL4A	P2T-E	Human	Esophagus	ESCC	6.48e-32	6.33e-01	0.1177
8266	UBL4A	P4T-E	Human	Esophagus	ESCC	3.44e-19	4.16e-01	0.1323
8266	UBL4A	P5T-E	Human	Esophagus	ESCC	2.05e-23	4.75e-01	0.1327
8266	UBL4A	P8T-E	Human	Esophagus	ESCC	1.84e-22	2.36e-01	0.0889
8266	UBL4A	P9T-E	Human	Esophagus	ESCC	1.66e-17	3.76e-01	0.1131
8266	UBL4A	P10T-E	Human	Esophagus	ESCC	3.69e-39	6.09e-01	0.116
8266	UBL4A	P11T-E	Human	Esophagus	ESCC	6.89e-12	5.76e-01	0.1426
8266	UBL4A	P12T-E	Human	Esophagus	ESCC	1.40e-32	5.51e-01	0.1122
8266	UBL4A	P15T-E	Human	Esophagus	ESCC	4.42e-11	3.35e-01	0.1149
8266	UBL4A	P16T-E	Human	Esophagus	ESCC	2.43e-22	2.67e-01	0.1153
8266	UBL4A	P17T-E	Human	Esophagus	ESCC	1.30e-14	5.56e-01	0.1278
8266	UBL4A	P19T-E	Human	Esophagus	ESCC	2.25e-11	1.15e+00	0.1662
8266	UBL4A	P20T-E	Human	Esophagus	ESCC	7.26e-22	3.57e-01	0.1124

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:0090150110	Esophagus	ESCC	establishment of protein localization to membrane	182/8552	260/18723	1.27e-15	8.19e-14	182
GO:000702914	Esophagus	ESCC	endoplasmic reticulum organization	65/8552	87/18723	3.28e-08	6.08e-07	65
GO:005120515	Esophagus	ESCC	protein insertion into membrane	46/8552	57/18723	5.90e-08	1.04e-06	46
GO:004504812	Esophagus	ESCC	protein insertion into ER membrane	21/8552	22/18723	8.75e-07	1.13e-05	21
GO:007181611	Esophagus	ESCC	tail-anchored membrane protein insertion into ER membrane	17/8552	17/18723	1.63e-06	1.95e-05	17
GO:009015012	Liver	HCC	establishment of protein localization to membrane	168/7958	260/18723	4.07e-13	2.13e-11	168
GO:000702911	Liver	HCC	endoplasmic reticulum organization	64/7958	87/18723	3.92e-09	1.04e-07	64
GO:005120511	Liver	HCC	protein insertion into membrane	41/7958	57/18723	6.42e-06	7.83e-05	41
GO:0071816	Liver	HCC	tail-anchored membrane protein insertion into ER membrane	15/7958	17/18723	1.31e-04	1.07e-03	15
GO:00450481	Liver	HCC	protein insertion into ER membrane	18/7958	22/18723	1.91e-04	1.49e-03	18
GO:009015018	Oral cavity	OSCC	establishment of protein localization to membrane	163/7305	260/18723	7.13e-15	4.47e-13	163
GO:00070294	Oral cavity	OSCC	endoplasmic reticulum organization	58/7305	87/18723	1.59e-07	2.61e-06	58
GO:00512056	Oral cavity	OSCC	protein insertion into membrane	40/7305	57/18723	1.81e-06	2.34e-05	40
GO:00450482	Oral cavity	OSCC	protein insertion into ER membrane	17/7305	22/18723	2.99e-04	1.87e-03	17
GO:00718162	Oral cavity	OSCC	tail-anchored membrane protein insertion into ER membrane	14/7305	17/18723	3.31e-04	2.04e-03	14
GO:009015019	Oral cavity	LP	establishment of protein localization to membrane	128/4623	260/18723	7.19e-18	1.19e-15	128
GO:005120514	Oral cavity	LP	protein insertion into membrane	35/4623	57/18723	4.38e-09	1.86e-07	35
GO:000702913	Oral cavity	LP	endoplasmic reticulum organization	41/4623	87/18723	4.49e-06	9.16e-05	41
GO:004504811	Oral cavity	LP	protein insertion into ER membrane	15/4623	22/18723	2.08e-05	3.44e-04	15
GO:00718161	Oral cavity	LP	tail-anchored membrane protein insertion into ER membrane	12/4623	17/18723	8.70e-05	1.10e-03	12

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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

UBL4A

insertion

Frame_Shift_Ins

novel

c.385_386insCAATCATTTTG

p.Arg129ProfsTer6

p.R129Pfs*6

P11441

protein_coding

TCGA-E9-A1NI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

UBL4A

SNV

Missense_Mutation

rs141549549

c.422N>A

p.Arg141His

p.R141H

P11441

protein_coding

tolerated(0.39)

probably_damaging(0.991)

TCGA-HM-A4S6-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

UBL4A

SNV

Missense_Mutation

c.255N>T

p.Gln85His

p.Q85H

P11441

protein_coding

tolerated(0.39)

benign(0)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

UBL4A

SNV

Missense_Mutation

c.331N>T

p.Asp111Tyr

p.D111Y

P11441

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

UBL4A

SNV

Missense_Mutation

rs782395991

c.326N>T

p.Ala109Val

p.A109V

P11441

protein_coding

deleterious(0.05)

benign(0)

TCGA-B5-A0K4-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

UBL4A

SNV

Missense_Mutation

rs782531758

c.170N>T

p.Ser57Leu

p.S57L

P11441

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-B5-A0K9-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

UBL4A

SNV

Missense_Mutation

rs782283486

c.265G>A

p.Asp89Asn

p.D89N

P11441

protein_coding

tolerated(0.35)

benign(0.054)

TCGA-BK-A0CC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Chemotherapy

taxol

UBL4A

SNV

Missense_Mutation

c.362N>T

p.Arg121Met

p.R121M

P11441

protein_coding

deleterious(0)

possibly_damaging(0.781)

TCGA-D1-A0ZO-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

UBL4A

SNV

Missense_Mutation

c.282N>T

p.Gln94His

p.Q94H

P11441

protein_coding

tolerated(0.11)

benign(0.001)

TCGA-D1-A0ZO-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

UBL4A

SNV

Missense_Mutation

novel

c.427N>A

p.Leu143Met

p.L143M

P11441

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-EY-A1GI-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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