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: UACA

Gene summary for UACA

Gene summary.

Gene information	Species	Human
	Gene symbol	UACA
	Gene ID	55075
	Gene name	uveal autoantigen with coiled-coil domains and ankyrin repeats
	Gene Alias	NUCLING
	Cytomap	15q23
	Gene Type	protein-coding
	GO ID	GO:0006508
	UniProtAcc	Q9BZF9

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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
55075	UACA	LZE2T	Human	Esophagus	ESCC	1.87e-03	2.90e-01	0.082
55075	UACA	LZE4T	Human	Esophagus	ESCC	1.87e-06	1.30e-01	0.0811
55075	UACA	LZE7T	Human	Esophagus	ESCC	1.77e-02	1.77e-01	0.0667
55075	UACA	LZE22T	Human	Esophagus	ESCC	2.28e-04	3.68e-01	0.068
55075	UACA	LZE24T	Human	Esophagus	ESCC	5.57e-18	2.76e-01	0.0596
55075	UACA	LZE21T	Human	Esophagus	ESCC	5.27e-03	2.04e-01	0.0655
55075	UACA	P1T-E	Human	Esophagus	ESCC	4.22e-04	5.97e-01	0.0875
55075	UACA	P2T-E	Human	Esophagus	ESCC	1.04e-35	6.67e-01	0.1177
55075	UACA	P4T-E	Human	Esophagus	ESCC	2.02e-17	4.87e-01	0.1323
55075	UACA	P8T-E	Human	Esophagus	ESCC	4.44e-29	5.90e-01	0.0889
55075	UACA	P9T-E	Human	Esophagus	ESCC	2.82e-15	4.95e-01	0.1131
55075	UACA	P10T-E	Human	Esophagus	ESCC	2.46e-30	6.30e-01	0.116
55075	UACA	P11T-E	Human	Esophagus	ESCC	1.63e-11	4.89e-01	0.1426
55075	UACA	P12T-E	Human	Esophagus	ESCC	7.03e-29	6.40e-01	0.1122
55075	UACA	P15T-E	Human	Esophagus	ESCC	1.86e-15	3.81e-01	0.1149
55075	UACA	P16T-E	Human	Esophagus	ESCC	9.48e-27	4.73e-01	0.1153
55075	UACA	P17T-E	Human	Esophagus	ESCC	8.32e-04	2.27e-01	0.1278
55075	UACA	P19T-E	Human	Esophagus	ESCC	2.91e-02	3.91e-01	0.1662
55075	UACA	P20T-E	Human	Esophagus	ESCC	2.56e-04	2.41e-01	0.1124
55075	UACA	P21T-E	Human	Esophagus	ESCC	4.46e-05	2.38e-01	0.1617

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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
Prostate		BPH: Benign Prostatic Hyperplasia
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:0045862111	Esophagus	ESCC	positive regulation of proteolysis	256/8552	372/18723	7.88e-20	9.43e-18	256
GO:2000116111	Esophagus	ESCC	regulation of cysteine-type endopeptidase activity	158/8552	235/18723	1.67e-11	5.90e-10	158
GO:0043281111	Esophagus	ESCC	regulation of cysteine-type endopeptidase activity involved in apoptotic process	143/8552	209/18723	2.12e-11	7.31e-10	143
GO:0010952111	Esophagus	ESCC	positive regulation of peptidase activity	133/8552	197/18723	4.31e-10	1.14e-08	133
GO:0052547111	Esophagus	ESCC	regulation of peptidase activity	275/8552	461/18723	7.54e-10	1.88e-08	275
GO:0052548111	Esophagus	ESCC	regulation of endopeptidase activity	253/8552	432/18723	3.68e-08	6.78e-07	253
GO:0010950111	Esophagus	ESCC	positive regulation of endopeptidase activity	116/8552	179/18723	1.77e-07	2.79e-06	116
GO:0043280110	Esophagus	ESCC	positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	84/8552	129/18723	6.38e-06	6.55e-05	84
GO:2001056110	Esophagus	ESCC	positive regulation of cysteine-type endopeptidase activity	94/8552	148/18723	8.87e-06	8.59e-05	94
GO:00380615	Esophagus	ESCC	NIK/NF-kappaB signaling	81/8552	143/18723	5.33e-03	2.00e-02	81
GO:00458627	Liver	NAFLD	positive regulation of proteolysis	65/1882	372/18723	6.58e-06	2.29e-04	65
GO:00525477	Liver	NAFLD	regulation of peptidase activity	72/1882	461/18723	1.03e-04	2.03e-03	72
GO:00525487	Liver	NAFLD	regulation of endopeptidase activity	67/1882	432/18723	2.17e-04	3.70e-03	67
GO:004586222	Liver	HCC	positive regulation of proteolysis	232/7958	372/18723	5.66e-15	3.98e-13	232
GO:004328112	Liver	HCC	regulation of cysteine-type endopeptidase activity involved in apoptotic process	125/7958	209/18723	3.12e-07	5.42e-06	125
GO:200011612	Liver	HCC	regulation of cysteine-type endopeptidase activity	137/7958	235/18723	6.91e-07	1.08e-05	137
GO:005254722	Liver	HCC	regulation of peptidase activity	247/7958	461/18723	8.28e-07	1.27e-05	247
GO:005254822	Liver	HCC	regulation of endopeptidase activity	230/7958	432/18723	3.58e-06	4.68e-05	230
GO:001095212	Liver	HCC	positive regulation of peptidase activity	110/7958	197/18723	1.04e-04	8.98e-04	110
GO:001095012	Liver	HCC	positive regulation of endopeptidase activity	96/7958	179/18723	1.68e-03	8.79e-03	96

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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

UACA

SNV

Missense_Mutation

c.1948T>A

p.Leu650Ile

p.L650I

Q9BZF9

protein_coding

tolerated(0.18)

benign(0.017)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UACA

SNV

Missense_Mutation

rs143107777

c.2314N>G

p.Thr772Ala

p.T772A

Q9BZF9

protein_coding

deleterious(0.03)

possibly_damaging(0.839)

TCGA-AC-A2QI-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cytoxan

UACA

SNV

Missense_Mutation

rs753763851

c.2704G>T

p.Asp902Tyr

p.D902Y

Q9BZF9

protein_coding

deleterious(0)

benign(0.219)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UACA

SNV

Missense_Mutation

novel

c.2408T>G

p.Phe803Cys

p.F803C

Q9BZF9

protein_coding

tolerated(0.08)

possibly_damaging(0.619)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UACA

SNV

Missense_Mutation

c.2173G>A

p.Asp725Asn

p.D725N

Q9BZF9

protein_coding

deleterious(0)

possibly_damaging(0.905)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UACA

SNV

Missense_Mutation

c.3154N>C

p.Glu1052Gln

p.E1052Q

Q9BZF9

protein_coding

deleterious(0.01)

probably_damaging(0.998)

TCGA-AN-A0XW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

UACA

SNV

Missense_Mutation

c.844N>T

p.Asp282Tyr

p.D282Y

Q9BZF9

protein_coding

deleterious(0.02)

possibly_damaging(0.526)

TCGA-BH-A0B4-01

Breast

breast invasive carcinoma

Male

>=65

III/IV

Hormone Therapy

tamoxiphen

UACA

SNV

Missense_Mutation

c.4181N>T

p.Gly1394Val

p.G1394V

Q9BZF9

protein_coding

deleterious(0)

possibly_damaging(0.875)

TCGA-BH-A0HX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adrimycin

UACA

SNV

Missense_Mutation

c.3480G>C

p.Lys1160Asn

p.K1160N

Q9BZF9

protein_coding

deleterious(0)

possibly_damaging(0.776)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UACA

SNV

Missense_Mutation

rs201992560

c.3758A>C

p.Lys1253Thr

p.K1253T

Q9BZF9

protein_coding

deleterious(0)

probably_damaging(0.962)

TCGA-E2-A14S-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

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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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