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: ZNF451

Gene summary for ZNF451

Gene summary.

Gene information	Species	Human
	Gene symbol	ZNF451
	Gene ID	26036
	Gene name	zinc finger protein 451
	Gene Alias	COASTER
	Cytomap	6p12.1
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	Q96JY2

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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
26036	ZNF451	LZE2T	Human	Esophagus	ESCC	9.68e-06	5.80e-01	0.082
26036	ZNF451	LZE4T	Human	Esophagus	ESCC	7.60e-15	3.42e-01	0.0811
26036	ZNF451	LZE7T	Human	Esophagus	ESCC	3.13e-20	1.11e+00	0.0667
26036	ZNF451	LZE20T	Human	Esophagus	ESCC	5.76e-07	2.17e-01	0.0662
26036	ZNF451	LZE22T	Human	Esophagus	ESCC	3.16e-02	1.65e-01	0.068
26036	ZNF451	LZE24T	Human	Esophagus	ESCC	1.00e-09	2.70e-01	0.0596
26036	ZNF451	LZE6T	Human	Esophagus	ESCC	4.05e-02	1.96e-01	0.0845
26036	ZNF451	P1T-E	Human	Esophagus	ESCC	4.05e-08	3.48e-01	0.0875
26036	ZNF451	P2T-E	Human	Esophagus	ESCC	1.31e-20	2.55e-01	0.1177
26036	ZNF451	P4T-E	Human	Esophagus	ESCC	5.30e-16	3.87e-01	0.1323
26036	ZNF451	P5T-E	Human	Esophagus	ESCC	4.64e-16	2.05e-01	0.1327
26036	ZNF451	P8T-E	Human	Esophagus	ESCC	2.81e-18	2.91e-01	0.0889
26036	ZNF451	P9T-E	Human	Esophagus	ESCC	1.98e-18	3.04e-01	0.1131
26036	ZNF451	P10T-E	Human	Esophagus	ESCC	1.07e-22	3.38e-01	0.116
26036	ZNF451	P11T-E	Human	Esophagus	ESCC	1.43e-07	4.81e-01	0.1426
26036	ZNF451	P12T-E	Human	Esophagus	ESCC	6.51e-26	4.31e-01	0.1122
26036	ZNF451	P15T-E	Human	Esophagus	ESCC	1.89e-18	1.80e-01	0.1149
26036	ZNF451	P16T-E	Human	Esophagus	ESCC	6.39e-27	3.59e-01	0.1153
26036	ZNF451	P17T-E	Human	Esophagus	ESCC	4.01e-08	3.68e-01	0.1278
26036	ZNF451	P19T-E	Human	Esophagus	ESCC	8.68e-03	3.19e-01	0.1662

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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
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
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:19038443	Liver	NAFLD	regulation of cellular response to transforming growth factor beta stimulus	23/1882	131/18723	5.62e-03	4.29e-02	23
GO:00064731	Liver	Cirrhotic	protein acetylation	84/4634	201/18723	7.50e-08	2.25e-06	84
GO:00183941	Liver	Cirrhotic	peptidyl-lysine acetylation	73/4634	169/18723	1.08e-07	3.07e-06	73
GO:00435431	Liver	Cirrhotic	protein acylation	95/4634	243/18723	4.73e-07	1.07e-05	95
GO:00182051	Liver	Cirrhotic	peptidyl-lysine modification	134/4634	376/18723	1.29e-06	2.59e-05	134
GO:007155911	Liver	Cirrhotic	response to transforming growth factor beta	96/4634	256/18723	3.55e-06	6.09e-05	96
GO:00064751	Liver	Cirrhotic	internal protein amino acid acetylation	65/4634	160/18723	6.66e-06	1.04e-04	65
GO:007156011	Liver	Cirrhotic	cellular response to transforming growth factor beta stimulus	93/4634	250/18723	7.34e-06	1.13e-04	93
GO:00183931	Liver	Cirrhotic	internal peptidyl-lysine acetylation	64/4634	158/18723	8.75e-06	1.29e-04	64
GO:001657011	Liver	Cirrhotic	histone modification	154/4634	463/18723	1.92e-05	2.57e-04	154
GO:00165731	Liver	Cirrhotic	histone acetylation	61/4634	152/18723	1.97e-05	2.62e-04	61
GO:2000756	Liver	Cirrhotic	regulation of peptidyl-lysine acetylation	30/4634	63/18723	6.83e-05	7.74e-04	30
GO:003105611	Liver	Cirrhotic	regulation of histone modification	59/4634	152/18723	8.28e-05	9.02e-04	59
GO:1901983	Liver	Cirrhotic	regulation of protein acetylation	34/4634	77/18723	1.53e-04	1.46e-03	34
GO:000717911	Liver	Cirrhotic	transforming growth factor beta receptor signaling pathway	71/4634	198/18723	3.02e-04	2.65e-03	71
GO:19019841	Liver	Cirrhotic	negative regulation of protein acetylation	13/4634	24/18723	1.89e-03	1.19e-02	13
GO:0006367	Liver	Cirrhotic	transcription initiation from RNA polymerase II promoter	31/4634	77/18723	1.91e-03	1.20e-02	31
GO:190384411	Liver	Cirrhotic	regulation of cellular response to transforming growth factor beta stimulus	47/4634	131/18723	2.87e-03	1.65e-02	47
GO:000717811	Liver	Cirrhotic	transmembrane receptor protein serine/threonine kinase signaling pathway	111/4634	355/18723	2.98e-03	1.70e-02	111
GO:0035065	Liver	Cirrhotic	regulation of histone acetylation	23/4634	54/18723	3.02e-03	1.72e-02	23

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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

ZNF451

SNV

Missense_Mutation

rs750718545

c.2891N>A

p.Arg964His

p.R964H

Q9Y4E5

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-B6-A1KI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ZNF451

SNV

Missense_Mutation

novel

c.992N>T

p.Thr331Ile

p.T331I

Q9Y4E5

protein_coding

deleterious(0)

possibly_damaging(0.845)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

ZNF451

SNV

Missense_Mutation

novel

c.1715N>T

p.Pro572Leu

p.P572L

Q9Y4E5

protein_coding

deleterious(0.02)

benign(0.322)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

ZNF451

SNV

Missense_Mutation

c.2824N>C

p.Phe942Leu

p.F942L

Q9Y4E5

protein_coding

deleterious(0)

probably_damaging(0.971)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ZNF451

SNV

Missense_Mutation

c.1215N>A

p.Ser405Arg

p.S405R

Q9Y4E5

protein_coding

tolerated(0.14)

benign(0.06)

TCGA-D8-A1JE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamicin

ZNF451

SNV

Missense_Mutation

c.877N>T

p.Pro293Ser

p.P293S

Q9Y4E5

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-E9-A1RH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

ZNF451

insertion

Frame_Shift_Ins

novel

c.1829_1830insAGGCAGAAGAGCC

p.Cys611GlyfsTer6

p.C611Gfs*6

Q9Y4E5

protein_coding

TCGA-B6-A0IA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ZNF451

SNV

Missense_Mutation

novel

c.2642A>G

p.Tyr881Cys

p.Y881C

Q9Y4E5

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.635)

TCGA-5M-AAT6-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Unknown

ZNF451

SNV

Missense_Mutation

c.899N>T

p.Ala300Val

p.A300V

Q9Y4E5

protein_coding

tolerated(0.12)

probably_damaging(0.971)

TCGA-A6-6141-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

5-fu

ZNF451

SNV

Missense_Mutation

novel

c.1910N>C

p.Ser637Thr

p.S637T

Q9Y4E5

protein_coding

tolerated(0.31)

benign(0.084)

TCGA-AA-3845-01

Colorectum

colon adenocarcinoma

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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