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: ZC3H18

Gene summary for ZC3H18

Gene summary.

Gene information	Species	Human
	Gene symbol	ZC3H18
	Gene ID	124245
	Gene name	zinc finger CCCH-type containing 18
	Gene Alias	NHN1
	Cytomap	16q24.2
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	B4DTK7

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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
124245	ZC3H18	LZE4T	Human	Esophagus	ESCC	2.67e-06	2.97e-01	0.0811
124245	ZC3H18	LZE7T	Human	Esophagus	ESCC	1.49e-06	3.78e-01	0.0667
124245	ZC3H18	LZE8T	Human	Esophagus	ESCC	7.56e-04	1.28e-01	0.067
124245	ZC3H18	LZE22T	Human	Esophagus	ESCC	2.08e-05	3.31e-01	0.068
124245	ZC3H18	LZE24T	Human	Esophagus	ESCC	2.90e-15	2.52e-01	0.0596
124245	ZC3H18	LZE21T	Human	Esophagus	ESCC	3.19e-03	1.93e-01	0.0655
124245	ZC3H18	P1T-E	Human	Esophagus	ESCC	1.83e-10	6.13e-01	0.0875
124245	ZC3H18	P2T-E	Human	Esophagus	ESCC	4.07e-22	4.64e-01	0.1177
124245	ZC3H18	P4T-E	Human	Esophagus	ESCC	6.44e-10	2.56e-01	0.1323
124245	ZC3H18	P5T-E	Human	Esophagus	ESCC	2.49e-12	2.19e-01	0.1327
124245	ZC3H18	P8T-E	Human	Esophagus	ESCC	3.10e-17	3.68e-01	0.0889
124245	ZC3H18	P9T-E	Human	Esophagus	ESCC	2.35e-06	1.57e-01	0.1131
124245	ZC3H18	P10T-E	Human	Esophagus	ESCC	1.46e-20	3.85e-01	0.116
124245	ZC3H18	P11T-E	Human	Esophagus	ESCC	7.78e-09	3.31e-01	0.1426
124245	ZC3H18	P12T-E	Human	Esophagus	ESCC	2.45e-20	4.59e-01	0.1122
124245	ZC3H18	P15T-E	Human	Esophagus	ESCC	2.36e-19	4.20e-01	0.1149
124245	ZC3H18	P16T-E	Human	Esophagus	ESCC	1.20e-13	2.39e-01	0.1153
124245	ZC3H18	P17T-E	Human	Esophagus	ESCC	2.20e-04	2.60e-01	0.1278
124245	ZC3H18	P19T-E	Human	Esophagus	ESCC	1.57e-02	2.31e-01	0.1662
124245	ZC3H18	P20T-E	Human	Esophagus	ESCC	2.16e-12	3.23e-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
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:0009896113	Thyroid	PTC	positive regulation of catabolic process	278/5968	492/18723	3.35e-30	2.64e-27	278
GO:0031331113	Thyroid	PTC	positive regulation of cellular catabolic process	249/5968	427/18723	5.28e-30	3.58e-27	249
GO:0006401112	Thyroid	PTC	RNA catabolic process	163/5968	278/18723	2.13e-20	3.27e-18	163
GO:0034655112	Thyroid	PTC	nucleobase-containing compound catabolic process	211/5968	407/18723	2.72e-17	2.52e-15	211
GO:0046700111	Thyroid	PTC	heterocycle catabolic process	221/5968	445/18723	2.43e-15	1.72e-13	221
GO:0044270111	Thyroid	PTC	cellular nitrogen compound catabolic process	223/5968	451/18723	3.34e-15	2.31e-13	223
GO:0019439111	Thyroid	PTC	aromatic compound catabolic process	225/5968	467/18723	8.51e-14	4.71e-12	225
GO:1901361111	Thyroid	PTC	organic cyclic compound catabolic process	231/5968	495/18723	2.55e-12	1.12e-10	231
GO:0043487111	Thyroid	PTC	regulation of RNA stability	97/5968	170/18723	9.51e-12	3.97e-10	97
GO:005077919	Thyroid	PTC	RNA destabilization	53/5968	88/18723	3.91e-08	8.51e-07	53
GO:0009896210	Thyroid	ATC	positive regulation of catabolic process	290/6293	492/18723	2.15e-31	1.94e-28	290
GO:0031331210	Thyroid	ATC	positive regulation of cellular catabolic process	258/6293	427/18723	2.09e-30	1.65e-27	258
GO:000640127	Thyroid	ATC	RNA catabolic process	165/6293	278/18723	8.45e-19	1.14e-16	165
GO:003465525	Thyroid	ATC	nucleobase-containing compound catabolic process	217/6293	407/18723	1.20e-16	1.04e-14	217
GO:004670024	Thyroid	ATC	heterocycle catabolic process	228/6293	445/18723	7.26e-15	4.50e-13	228
GO:004427025	Thyroid	ATC	cellular nitrogen compound catabolic process	229/6293	451/18723	2.25e-14	1.27e-12	229
GO:001943924	Thyroid	ATC	aromatic compound catabolic process	232/6293	467/18723	3.05e-13	1.44e-11	232
GO:190136124	Thyroid	ATC	organic cyclic compound catabolic process	238/6293	495/18723	1.12e-11	4.12e-10	238
GO:004348725	Thyroid	ATC	regulation of RNA stability	97/6293	170/18723	2.68e-10	7.70e-09	97
GO:0050779110	Thyroid	ATC	RNA destabilization	53/6293	88/18723	2.75e-07	4.20e-06	53

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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

ZC3H18

SNV

Missense_Mutation

novel

c.1645N>T

p.Pro549Ser

p.P549S

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.998)

TCGA-A2-A3XW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamyicin

ZC3H18

SNV

Missense_Mutation

novel

c.2774N>G

p.Lys925Arg

p.K925R

protein_coding

deleterious_low_confidence(0.03)

probably_damaging(0.991)

TCGA-BH-A0B7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

ZC3H18

SNV

Missense_Mutation

rs749335369

c.2657N>T

p.Ser886Leu

p.S886L

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.725)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

ZC3H18

insertion

Frame_Shift_Ins

novel

c.1480_1481insTTCATGTCTCTCAGGCATCTCCCCATTCACATGCTTCATGTCAG

p.Arg494LeufsTer55

p.R494Lfs*55

protein_coding

TCGA-AO-A0J5-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate

zoledronic

ZC3H18

insertion

In_Frame_Ins

novel

c.2306_2307insAGCAGCATATGGGCAGGGCAGACTCAGGTGCCAGTCCTGTGT

p.Arg769_Ser770insAlaAlaTyrGlyGlnGlyArgLeuArgCysGlnSerCysVal

p.R769_S770insAAYGQGRLRCQSCV

protein_coding

TCGA-BH-A0H7-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

ZC3H18

SNV

Missense_Mutation

novel

c.1696C>T

p.Arg566Trp

p.R566W

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.984)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ZC3H18

SNV

Missense_Mutation

novel

c.2908C>T

p.Arg970Trp

p.R970W

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.997)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ZC3H18

SNV

Missense_Mutation

rs267604676

c.1133G>A

p.Arg378Gln

p.R378Q

protein_coding

tolerated_low_confidence(0.05)

possibly_damaging(0.67)

TCGA-FU-A3TQ-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

ZC3H18

SNV

Missense_Mutation

c.2752N>T

p.Pro918Ser

p.P918S

protein_coding

deleterious_low_confidence(0.05)

probably_damaging(0.998)

TCGA-JX-A3Q0-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

ZC3H18

SNV

Missense_Mutation

rs201777324

c.1550N>A

p.Arg517His

p.R517H

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.966)

TCGA-LP-A7HU-01

Cervix

cervical & endocervical cancer

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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