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: ZDHHC5

Gene summary for ZDHHC5

Gene summary.

Gene information	Species	Human
	Gene symbol	ZDHHC5
	Gene ID	25921
	Gene name	zinc finger DHHC-type palmitoyltransferase 5
	Gene Alias	DHHC5
	Cytomap	11q12.1
	Gene Type	protein-coding
	GO ID	GO:0002221
	UniProtAcc	A0A024R546

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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
25921	ZDHHC5	HTA11_2487_2000001011	Human	Colorectum	SER	6.54e-06	3.58e-01	-0.1808
25921	ZDHHC5	HTA11_1938_2000001011	Human	Colorectum	AD	8.27e-10	4.71e-01	-0.0811
25921	ZDHHC5	HTA11_347_2000001011	Human	Colorectum	AD	9.77e-15	4.42e-01	-0.1954
25921	ZDHHC5	HTA11_3361_2000001011	Human	Colorectum	AD	1.39e-03	1.98e-01	-0.1207
25921	ZDHHC5	HTA11_696_2000001011	Human	Colorectum	AD	1.37e-04	3.79e-01	-0.1464
25921	ZDHHC5	HTA11_1391_2000001011	Human	Colorectum	AD	9.20e-09	4.78e-01	-0.059
25921	ZDHHC5	HTA11_546_2000001011	Human	Colorectum	AD	5.88e-04	2.66e-01	-0.0842
25921	ZDHHC5	HTA11_10711_2000001011	Human	Colorectum	AD	7.71e-03	1.69e-02	0.0338
25921	ZDHHC5	HTA11_99999965104_69814	Human	Colorectum	MSS	1.63e-05	3.30e-01	0.281
25921	ZDHHC5	A015-C-203	Human	Colorectum	FAP	1.08e-06	-1.71e-01	-0.1294
25921	ZDHHC5	A015-C-104	Human	Colorectum	FAP	2.83e-08	-1.99e-01	-0.1899
25921	ZDHHC5	A001-C-014	Human	Colorectum	FAP	1.24e-02	-1.48e-01	0.0135
25921	ZDHHC5	A002-C-116	Human	Colorectum	FAP	1.43e-06	-1.24e-01	-0.0452
25921	ZDHHC5	F034	Human	Colorectum	FAP	4.42e-05	-1.10e-01	-0.0665
25921	ZDHHC5	F072B	Human	Colorectum	FAP	2.79e-04	-1.73e-01	0.257
25921	ZDHHC5	LZE2T	Human	Esophagus	ESCC	3.14e-04	4.06e-01	0.082
25921	ZDHHC5	LZE7T	Human	Esophagus	ESCC	2.13e-02	1.04e-01	0.0667
25921	ZDHHC5	LZE22T	Human	Esophagus	ESCC	4.19e-04	2.27e-01	0.068
25921	ZDHHC5	LZE24T	Human	Esophagus	ESCC	1.29e-11	3.41e-01	0.0596
25921	ZDHHC5	P1T-E	Human	Esophagus	ESCC	3.83e-07	2.73e-01	0.0875

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
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:0072659	Colorectum	AD	protein localization to plasma membrane	122/3918	284/18723	2.86e-17	1.49e-14	122
GO:1990778	Colorectum	AD	protein localization to cell periphery	129/3918	333/18723	5.51e-14	1.15e-11	129
GO:1903829	Colorectum	AD	positive regulation of cellular protein localization	110/3918	276/18723	4.58e-13	8.44e-11	110
GO:1905475	Colorectum	AD	regulation of protein localization to membrane	73/3918	175/18723	3.37e-10	2.93e-08	73
GO:1903076	Colorectum	AD	regulation of protein localization to plasma membrane	48/3918	104/18723	7.17e-09	4.36e-07	48
GO:1904375	Colorectum	AD	regulation of protein localization to cell periphery	54/3918	125/18723	1.52e-08	9.00e-07	54
GO:1905477	Colorectum	AD	positive regulation of protein localization to membrane	46/3918	106/18723	1.47e-07	6.64e-06	46
GO:1903078	Colorectum	AD	positive regulation of protein localization to plasma membrane	28/3918	62/18723	1.57e-05	3.34e-04	28
GO:1904377	Colorectum	AD	positive regulation of protein localization to cell periphery	30/3918	69/18723	1.98e-05	4.05e-04	30
GO:00726591	Colorectum	SER	protein localization to plasma membrane	92/2897	284/18723	6.36e-13	1.86e-10	92
GO:19038291	Colorectum	SER	positive regulation of cellular protein localization	86/2897	276/18723	3.61e-11	6.11e-09	86
GO:19907781	Colorectum	SER	protein localization to cell periphery	98/2897	333/18723	6.09e-11	9.57e-09	98
GO:19030761	Colorectum	SER	regulation of protein localization to plasma membrane	36/2897	104/18723	1.12e-06	5.18e-05	36
GO:19054751	Colorectum	SER	regulation of protein localization to membrane	52/2897	175/18723	1.31e-06	6.04e-05	52
GO:19043751	Colorectum	SER	regulation of protein localization to cell periphery	40/2897	125/18723	2.85e-06	1.16e-04	40
GO:19054771	Colorectum	SER	positive regulation of protein localization to membrane	33/2897	106/18723	3.83e-05	9.82e-04	33
GO:19030781	Colorectum	SER	positive regulation of protein localization to plasma membrane	22/2897	62/18723	8.58e-05	1.88e-03	22
GO:19043771	Colorectum	SER	positive regulation of protein localization to cell periphery	23/2897	69/18723	1.78e-04	3.30e-03	23
GO:00726592	Colorectum	MSS	protein localization to plasma membrane	113/3467	284/18723	3.23e-17	1.55e-14	113
GO:19907782	Colorectum	MSS	protein localization to cell periphery	120/3467	333/18723	2.02e-14	5.47e-12	120

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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

ZDHHC5

SNV

Missense_Mutation

rs766814291

c.2087C>T

p.Thr696Met

p.T696M

Q9C0B5

protein_coding

deleterious(0.03)

probably_damaging(0.912)

TCGA-A2-A0YH-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

ZDHHC5

SNV

Missense_Mutation

c.1519N>A

p.Ala507Thr

p.A507T

Q9C0B5

protein_coding

tolerated(0.14)

benign(0.031)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ZDHHC5

SNV

Missense_Mutation

c.1917N>G

p.Ser639Arg

p.S639R

Q9C0B5

protein_coding

tolerated(0.15)

probably_damaging(0.924)

TCGA-E2-A1B1-01

Breast

breast invasive carcinoma

Female

<65

I/II

Other, specify in notesbiphosphonate

zoledronic

ZDHHC5

SNV

Missense_Mutation

novel

c.1226N>G

p.Ser409Cys

p.S409C

Q9C0B5

protein_coding

deleterious(0.01)

probably_damaging(0.912)

TCGA-OL-A5DA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ZDHHC5

SNV

Missense_Mutation

c.2122N>T

p.Gly708Cys

p.G708C

Q9C0B5

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-OL-A5RZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

ZDHHC5

insertion

Frame_Shift_Ins

novel

c.964_965insCTCCATCTCTAAAACAGACTAAAATAAAAAATAGAAAAATTTTCTG

p.Arg322ProfsTer29

p.R322Pfs*29

Q9C0B5

protein_coding

TCGA-AN-A0FX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ZDHHC5

insertion

Frame_Shift_Ins

novel

c.225_226insGGAAAACATGTGGCAAGATCCACAG

p.Ala76GlyfsTer10

p.A76Gfs*10

Q9C0B5

protein_coding

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

ZDHHC5

SNV

Missense_Mutation

novel

c.1147N>C

p.Glu383Gln

p.E383Q

Q9C0B5

protein_coding

tolerated(0.33)

benign(0.015)

TCGA-EX-A1H6-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

ZDHHC5

SNV

Missense_Mutation

c.1508C>T

p.Ser503Leu

p.S503L

Q9C0B5

protein_coding

deleterious(0.01)

possibly_damaging(0.459)

TCGA-IR-A3LL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ZDHHC5

SNV

Missense_Mutation

c.1249N>G

p.His417Asp

p.H417D

Q9C0B5

protein_coding

tolerated(0.18)

benign(0.04)

TCGA-LP-A4AV-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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