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: ZCCHC17

Gene summary for ZCCHC17

Gene summary.

Gene information	Species	Human
	Gene symbol	ZCCHC17
	Gene ID	51538
	Gene name	zinc finger CCHC-type containing 17
	Gene Alias	HSPC251
	Cytomap	1p35.2
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	A0A087WXF8

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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
51538	ZCCHC17	LZE4T	Human	Esophagus	ESCC	1.49e-13	2.20e-01	0.0811
51538	ZCCHC17	LZE7T	Human	Esophagus	ESCC	1.54e-03	3.78e-01	0.0667
51538	ZCCHC17	LZE8T	Human	Esophagus	ESCC	4.56e-06	1.01e-01	0.067
51538	ZCCHC17	LZE20T	Human	Esophagus	ESCC	6.90e-06	2.75e-01	0.0662
51538	ZCCHC17	LZE24D1	Human	Esophagus	HGIN	1.05e-02	5.35e-01	0.054
51538	ZCCHC17	LZE24T	Human	Esophagus	ESCC	1.44e-14	5.01e-01	0.0596
51538	ZCCHC17	LZE6T	Human	Esophagus	ESCC	1.08e-07	3.48e-01	0.0845
51538	ZCCHC17	P1T-E	Human	Esophagus	ESCC	1.38e-05	4.42e-01	0.0875
51538	ZCCHC17	P2T-E	Human	Esophagus	ESCC	1.77e-39	7.43e-01	0.1177
51538	ZCCHC17	P4T-E	Human	Esophagus	ESCC	3.23e-26	6.30e-01	0.1323
51538	ZCCHC17	P5T-E	Human	Esophagus	ESCC	5.71e-19	4.81e-01	0.1327
51538	ZCCHC17	P8T-E	Human	Esophagus	ESCC	1.09e-25	4.14e-01	0.0889
51538	ZCCHC17	P9T-E	Human	Esophagus	ESCC	6.48e-16	1.72e-01	0.1131
51538	ZCCHC17	P10T-E	Human	Esophagus	ESCC	7.36e-35	6.94e-01	0.116
51538	ZCCHC17	P11T-E	Human	Esophagus	ESCC	1.97e-13	6.05e-01	0.1426
51538	ZCCHC17	P12T-E	Human	Esophagus	ESCC	1.84e-18	3.26e-01	0.1122
51538	ZCCHC17	P15T-E	Human	Esophagus	ESCC	1.39e-14	4.23e-01	0.1149
51538	ZCCHC17	P16T-E	Human	Esophagus	ESCC	2.40e-23	3.81e-01	0.1153
51538	ZCCHC17	P17T-E	Human	Esophagus	ESCC	3.23e-09	4.42e-01	0.1278
51538	ZCCHC17	P19T-E	Human	Esophagus	ESCC	2.09e-04	7.56e-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
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:0006401110	Esophagus	ESCC	RNA catabolic process	204/8552	278/18723	3.39e-21	5.66e-19	204
GO:0034655110	Esophagus	ESCC	nucleobase-containing compound catabolic process	272/8552	407/18723	2.92e-18	2.90e-16	272
GO:004670018	Esophagus	ESCC	heterocycle catabolic process	286/8552	445/18723	1.12e-15	7.47e-14	286
GO:004427019	Esophagus	ESCC	cellular nitrogen compound catabolic process	288/8552	451/18723	3.03e-15	1.79e-13	288
GO:001943918	Esophagus	ESCC	aromatic compound catabolic process	295/8552	467/18723	1.09e-14	5.98e-13	295
GO:190136118	Esophagus	ESCC	organic cyclic compound catabolic process	307/8552	495/18723	9.99e-14	4.80e-12	307
GO:0009895111	Esophagus	ESCC	negative regulation of catabolic process	201/8552	320/18723	3.88e-10	1.05e-08	201
GO:004348719	Esophagus	ESCC	regulation of RNA stability	117/8552	170/18723	7.91e-10	1.94e-08	117
GO:0031330111	Esophagus	ESCC	negative regulation of cellular catabolic process	166/8552	262/18723	5.17e-09	1.08e-07	166
GO:190236916	Esophagus	ESCC	negative regulation of RNA catabolic process	46/8552	75/18723	4.54e-03	1.78e-02	46
GO:190136111	Liver	Cirrhotic	organic cyclic compound catabolic process	213/4634	495/18723	1.58e-19	3.67e-17	213
GO:001943911	Liver	Cirrhotic	aromatic compound catabolic process	202/4634	467/18723	6.93e-19	1.28e-16	202
GO:004427011	Liver	Cirrhotic	cellular nitrogen compound catabolic process	195/4634	451/18723	2.99e-18	4.94e-16	195
GO:004670011	Liver	Cirrhotic	heterocycle catabolic process	192/4634	445/18723	7.17e-18	1.12e-15	192
GO:003465511	Liver	Cirrhotic	nucleobase-containing compound catabolic process	171/4634	407/18723	9.07e-15	9.33e-13	171
GO:000640111	Liver	Cirrhotic	RNA catabolic process	126/4634	278/18723	4.64e-14	4.10e-12	126
GO:000989512	Liver	Cirrhotic	negative regulation of catabolic process	121/4634	320/18723	1.21e-07	3.39e-06	121
GO:004348711	Liver	Cirrhotic	regulation of RNA stability	73/4634	170/18723	1.44e-07	3.87e-06	73
GO:003133012	Liver	Cirrhotic	negative regulation of cellular catabolic process	101/4634	262/18723	4.57e-07	1.05e-05	101
GO:190236911	Liver	Cirrhotic	negative regulation of RNA catabolic process	29/4634	75/18723	5.24e-03	2.69e-02	29

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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

ZCCHC17

SNV

Missense_Mutation

c.617N>C

p.Arg206Thr

p.R206T

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.634)

TCGA-IR-A3LA-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ZCCHC17

SNV

Missense_Mutation

novel

c.323N>G

p.Ser108Cys

p.S108C

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-VS-A9UH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ZCCHC17

SNV

Missense_Mutation

novel

c.214T>C

p.Ser72Pro

p.S72P

protein_coding

deleterious(0)

probably_damaging(0.956)

TCGA-AZ-4315-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

ZCCHC17

SNV

Missense_Mutation

rs762726112

c.203N>A

p.Arg68Gln

p.R68Q

protein_coding

tolerated(0.33)

benign(0.024)

TCGA-EI-6917-01

Colorectum

rectum adenocarcinoma

Male

<65

III/IV

Chemotherapy

5fluorouracil+oxaciplatina+l-folinian

ZCCHC17

SNV

Missense_Mutation

novel

c.782N>G

p.His261Arg

p.H261R

protein_coding

deleterious_low_confidence(0)

benign(0)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

ZCCHC17

SNV

Missense_Mutation

c.226N>C

p.Val76Leu

p.V76L

protein_coding

tolerated(0.08)

possibly_damaging(0.749)

TCGA-A5-A0GI-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

ZCCHC17

SNV

Missense_Mutation

rs762726112

c.203N>A

p.Arg68Gln

p.R68Q

protein_coding

tolerated(0.33)

benign(0.024)

TCGA-AX-A05Z-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

ZCCHC17

SNV

Missense_Mutation

rs762726112

c.203N>A

p.Arg68Gln

p.R68Q

protein_coding

tolerated(0.33)

benign(0.024)

TCGA-BS-A0UV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

ZCCHC17

SNV

Missense_Mutation

novel

c.329N>C

p.Lys110Thr

p.K110T

protein_coding

deleterious(0)

probably_damaging(0.987)

TCGA-EO-A22R-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

ZCCHC17

SNV

Missense_Mutation

rs776735412

c.194N>C

p.Leu65Pro

p.L65P

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-EY-A215-01

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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