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: ZFAND5

Gene summary for ZFAND5

Gene summary.

Gene information	Species	Human
	Gene symbol	ZFAND5
	Gene ID	7763
	Gene name	zinc finger AN1-type containing 5
	Gene Alias	ZA20D2
	Cytomap	9q21.13
	Gene Type	protein-coding
	GO ID	GO:0001501
	UniProtAcc	A0A024R219

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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
7763	ZFAND5	GSM4909285	Human	Breast	IDC	1.04e-03	-4.66e-02	0.21
7763	ZFAND5	GSM4909286	Human	Breast	IDC	2.01e-11	-2.59e-01	0.1081
7763	ZFAND5	GSM4909290	Human	Breast	IDC	2.83e-04	-3.96e-01	0.2096
7763	ZFAND5	GSM4909291	Human	Breast	IDC	5.92e-03	3.70e-01	0.1753
7763	ZFAND5	GSM4909294	Human	Breast	IDC	4.58e-09	-3.92e-01	0.2022
7763	ZFAND5	GSM4909296	Human	Breast	IDC	2.91e-34	-5.49e-01	0.1524
7763	ZFAND5	GSM4909297	Human	Breast	IDC	1.17e-23	-3.90e-01	0.1517
7763	ZFAND5	GSM4909298	Human	Breast	IDC	1.66e-08	-2.54e-01	0.1551
7763	ZFAND5	GSM4909301	Human	Breast	IDC	2.94e-11	-3.57e-01	0.1577
7763	ZFAND5	GSM4909302	Human	Breast	IDC	5.01e-14	-5.32e-01	0.1545
7763	ZFAND5	GSM4909304	Human	Breast	IDC	5.07e-23	-5.19e-01	0.1636
7763	ZFAND5	GSM4909306	Human	Breast	IDC	3.28e-05	-3.11e-01	0.1564
7763	ZFAND5	GSM4909307	Human	Breast	IDC	1.05e-09	-3.52e-01	0.1569
7763	ZFAND5	GSM4909309	Human	Breast	IDC	1.52e-02	-3.29e-01	0.0483
7763	ZFAND5	GSM4909311	Human	Breast	IDC	4.27e-42	-5.84e-01	0.1534
7763	ZFAND5	GSM4909312	Human	Breast	IDC	2.73e-20	-4.13e-01	0.1552
7763	ZFAND5	GSM4909315	Human	Breast	IDC	4.21e-03	-2.36e-01	0.21
7763	ZFAND5	GSM4909316	Human	Breast	IDC	6.49e-04	-5.38e-01	0.21
7763	ZFAND5	GSM4909319	Human	Breast	IDC	2.29e-46	-6.55e-01	0.1563
7763	ZFAND5	GSM4909320	Human	Breast	IDC	8.26e-13	-6.79e-01	0.1575

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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
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:00016678	Breast	Precancer	ameboidal-type cell migration	47/1080	475/18723	2.19e-04	3.35e-03	47
GO:00017017	Breast	Precancer	in utero embryonic development	35/1080	367/18723	2.47e-03	2.27e-02	35
GO:00605374	Breast	Precancer	muscle tissue development	37/1080	403/18723	3.60e-03	2.98e-02	37
GO:000166714	Breast	IDC	ameboidal-type cell migration	64/1434	475/18723	6.65e-06	2.05e-04	64
GO:006053711	Breast	IDC	muscle tissue development	50/1434	403/18723	4.91e-04	6.45e-03	50
GO:000170113	Breast	IDC	in utero embryonic development	42/1434	367/18723	5.85e-03	4.24e-02	42
GO:000166723	Breast	DCIS	ameboidal-type cell migration	62/1390	475/18723	9.60e-06	2.56e-04	62
GO:006053721	Breast	DCIS	muscle tissue development	50/1390	403/18723	2.39e-04	3.74e-03	50
GO:000170122	Breast	DCIS	in utero embryonic development	41/1390	367/18723	5.74e-03	4.13e-02	41
GO:00605376	Endometrium	AEH	muscle tissue development	83/2100	403/18723	2.57e-08	1.50e-06	83
GO:000166710	Endometrium	AEH	ameboidal-type cell migration	90/2100	475/18723	3.73e-07	1.57e-05	90
GO:00017019	Endometrium	AEH	in utero embryonic development	73/2100	367/18723	7.18e-07	2.63e-05	73
GO:00107616	Endometrium	AEH	fibroblast migration	14/2100	47/18723	4.51e-04	4.76e-03	14
GO:006053713	Endometrium	EEC	muscle tissue development	82/2168	403/18723	2.14e-07	9.38e-06	82
GO:000170114	Endometrium	EEC	in utero embryonic development	75/2168	367/18723	5.86e-07	2.16e-05	75
GO:000166716	Endometrium	EEC	ameboidal-type cell migration	91/2168	475/18723	7.87e-07	2.80e-05	91
GO:001076112	Endometrium	EEC	fibroblast migration	14/2168	47/18723	6.25e-04	6.14e-03	14
GO:000170119	Esophagus	ESCC	in utero embryonic development	243/8552	367/18723	1.00e-15	6.86e-14	243
GO:00480087	Esophagus	ESCC	platelet-derived growth factor receptor signaling pathway	42/8552	56/18723	7.62e-06	7.54e-05	42
GO:00603242	Esophagus	ESCC	face development	34/8552	44/18723	1.90e-05	1.67e-04	34

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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

ZFAND5

SNV

Missense_Mutation

c.359C>T

p.Ser120Leu

p.S120L

O76080

protein_coding

tolerated(0.37)

benign(0)

TCGA-GM-A2DO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

ZFAND5

SNV

Missense_Mutation

novel

c.545A>T

p.Asp182Val

p.D182V

O76080

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-S3-AA10-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

ZFAND5

SNV

Missense_Mutation

c.465N>A

p.Phe155Leu

p.F155L

O76080

protein_coding

deleterious(0.03)

probably_damaging(0.982)

TCGA-C5-A1M6-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ZFAND5

SNV

Missense_Mutation

c.397N>A

p.Gln133Lys

p.Q133K

O76080

protein_coding

tolerated(0.54)

benign(0.014)

TCGA-C5-A7XC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

ZFAND5

SNV

Missense_Mutation

novel

c.333N>C

p.Lys111Asn

p.K111N

O76080

protein_coding

tolerated(0.54)

benign(0.01)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

ZFAND5

SNV

Missense_Mutation

novel

c.314N>T

p.Ser105Ile

p.S105I

O76080

protein_coding

deleterious(0.02)

benign(0.204)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

ZFAND5

SNV

Missense_Mutation

c.468N>A

p.Met156Ile

p.M156I

O76080

protein_coding

tolerated(0.28)

benign(0.026)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

ZFAND5

SNV

Missense_Mutation

c.120N>T

p.Arg40Ser

p.R40S

O76080

protein_coding

deleterious(0)

probably_damaging(0.972)

TCGA-B5-A0JY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

ZFAND5

SNV

Missense_Mutation

novel

c.23C>T

p.Thr8Ile

p.T8I

O76080

protein_coding

deleterious(0)

probably_damaging(0.921)

TCGA-B5-A3FC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

ZFAND5

SNV

Missense_Mutation

c.79A>C

p.Asn27His

p.N27H

O76080

protein_coding

deleterious(0.02)

probably_damaging(0.983)

TCGA-D1-A103-01

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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