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: ZFAND2A

Gene summary for ZFAND2A

Gene summary.

Gene information	Species	Human
	Gene symbol	ZFAND2A
	Gene ID	90637
	Gene name	zinc finger AN1-type containing 2A
	Gene Alias	AIRAP
	Cytomap	7p22.3
	Gene Type	protein-coding
	GO ID	GO:0006508
	UniProtAcc	Q8N6M9

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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
90637	ZFAND2A	sample1	Human	Cervix	CC	7.81e-26	1.07e+00	0.0959
90637	ZFAND2A	T1	Human	Cervix	CC	1.33e-33	9.42e-01	0.0918
90637	ZFAND2A	LZE4T	Human	Esophagus	ESCC	4.45e-32	3.04e+00	0.0811
90637	ZFAND2A	LZE7T	Human	Esophagus	ESCC	8.72e-04	7.52e-02	0.0667
90637	ZFAND2A	LZE8T	Human	Esophagus	ESCC	9.65e-04	-2.00e-01	0.067
90637	ZFAND2A	LZE20T	Human	Esophagus	ESCC	4.22e-07	9.66e-01	0.0662
90637	ZFAND2A	LZE22T	Human	Esophagus	ESCC	4.85e-05	2.92e+00	0.068
90637	ZFAND2A	LZE24T	Human	Esophagus	ESCC	6.15e-05	5.51e-01	0.0596
90637	ZFAND2A	LZE6T	Human	Esophagus	ESCC	5.37e-07	1.15e+00	0.0845
90637	ZFAND2A	P2T-E	Human	Esophagus	ESCC	3.34e-23	6.96e-01	0.1177
90637	ZFAND2A	P4T-E	Human	Esophagus	ESCC	2.76e-56	3.74e+00	0.1323
90637	ZFAND2A	P5T-E	Human	Esophagus	ESCC	3.87e-72	3.76e+00	0.1327
90637	ZFAND2A	P8T-E	Human	Esophagus	ESCC	4.11e-07	7.48e-02	0.0889
90637	ZFAND2A	P9T-E	Human	Esophagus	ESCC	1.49e-07	6.45e-01	0.1131
90637	ZFAND2A	P10T-E	Human	Esophagus	ESCC	1.70e-10	1.83e-01	0.116
90637	ZFAND2A	P11T-E	Human	Esophagus	ESCC	7.10e-32	4.47e+00	0.1426
90637	ZFAND2A	P12T-E	Human	Esophagus	ESCC	1.85e-43	2.32e+00	0.1122
90637	ZFAND2A	P15T-E	Human	Esophagus	ESCC	1.12e-17	1.07e+00	0.1149
90637	ZFAND2A	P16T-E	Human	Esophagus	ESCC	1.61e-30	1.54e+00	0.1153
90637	ZFAND2A	P17T-E	Human	Esophagus	ESCC	3.77e-03	4.88e-01	0.1278

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
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:004217610	Cervix	CC	regulation of protein catabolic process	104/2311	391/18723	9.39e-15	9.36e-12	104
GO:004586210	Cervix	CC	positive regulation of proteolysis	95/2311	372/18723	1.84e-12	6.86e-10	95
GO:190336210	Cervix	CC	regulation of cellular protein catabolic process	72/2311	255/18723	5.98e-12	2.10e-09	72
GO:004573210	Cervix	CC	positive regulation of protein catabolic process	65/2311	231/18723	7.44e-11	1.39e-08	65
GO:001049810	Cervix	CC	proteasomal protein catabolic process	111/2311	490/18723	8.98e-11	1.58e-08	111
GO:00725949	Cervix	CC	establishment of protein localization to organelle	99/2311	422/18723	1.23e-10	2.11e-08	99
GO:000989610	Cervix	CC	positive regulation of catabolic process	109/2311	492/18723	5.26e-10	6.99e-08	109
GO:190305010	Cervix	CC	regulation of proteolysis involved in cellular protein catabolic process	60/2311	221/18723	1.82e-09	1.98e-07	60
GO:200005810	Cervix	CC	regulation of ubiquitin-dependent protein catabolic process	47/2311	164/18723	1.63e-08	1.25e-06	47
GO:004316110	Cervix	CC	proteasome-mediated ubiquitin-dependent protein catabolic process	91/2311	412/18723	1.65e-08	1.25e-06	91
GO:003133110	Cervix	CC	positive regulation of cellular catabolic process	91/2311	427/18723	9.64e-08	5.25e-06	91
GO:190336410	Cervix	CC	positive regulation of cellular protein catabolic process	43/2311	155/18723	1.80e-07	8.28e-06	43
GO:006113610	Cervix	CC	regulation of proteasomal protein catabolic process	48/2311	187/18723	4.63e-07	1.77e-05	48
GO:003243410	Cervix	CC	regulation of proteasomal ubiquitin-dependent protein catabolic process	38/2311	134/18723	4.99e-07	1.88e-05	38
GO:000660510	Cervix	CC	protein targeting	68/2311	314/18723	2.17e-06	6.55e-05	68
GO:19030528	Cervix	CC	positive regulation of proteolysis involved in cellular protein catabolic process	34/2311	133/18723	2.28e-05	4.01e-04	34
GO:200006010	Cervix	CC	positive regulation of ubiquitin-dependent protein catabolic process	29/2311	107/18723	2.77e-05	4.62e-04	29
GO:00324369	Cervix	CC	positive regulation of proteasomal ubiquitin-dependent protein catabolic process	25/2311	90/18723	6.22e-05	8.90e-04	25
GO:19018008	Cervix	CC	positive regulation of proteasomal protein catabolic process	29/2311	114/18723	9.71e-05	1.27e-03	29
GO:00709726	Cervix	CC	protein localization to endoplasmic reticulum	21/2311	74/18723	1.69e-04	2.00e-03	21

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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

ZFAND2A

SNV

Missense_Mutation

novel

c.157N>T

p.His53Tyr

p.H53Y

Q8N6M9

protein_coding

deleterious(0.02)

benign(0)

TCGA-C5-A8XJ-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

ZFAND2A

SNV

Missense_Mutation

c.283N>T

p.Ile95Phe

p.I95F

Q8N6M9

protein_coding

deleterious(0)

possibly_damaging(0.643)

TCGA-AZ-6608-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Unknown

ZFAND2A

SNV

Missense_Mutation

novel

c.196G>T

p.Val66Leu

p.V66L

Q8N6M9

protein_coding

tolerated(0.09)

benign(0.003)

TCGA-A5-A0G1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

ZFAND2A

SNV

Missense_Mutation

novel

c.196N>T

p.Val66Leu

p.V66L

Q8N6M9

protein_coding

tolerated(0.09)

benign(0.003)

TCGA-A5-A0GG-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

ZFAND2A

SNV

Missense_Mutation

novel

c.413G>A

p.Ser138Asn

p.S138N

Q8N6M9

protein_coding

tolerated(0.08)

benign(0.013)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

ZFAND2A

SNV

Missense_Mutation

novel

c.26N>G

p.His9Arg

p.H9R

Q8N6M9

protein_coding

deleterious(0.02)

possibly_damaging(0.703)

TCGA-AJ-A3BG-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

carboplatin

ZFAND2A

SNV

Missense_Mutation

c.91G>T

p.Asp31Tyr

p.D31Y

Q8N6M9

protein_coding

deleterious(0.02)

possibly_damaging(0.454)

TCGA-AX-A05Z-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

ZFAND2A

SNV

Missense_Mutation

novel

c.380G>T

p.Arg127Ile

p.R127I

Q8N6M9

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

ZFAND2A

SNV

Missense_Mutation

rs748607914

c.295N>T

p.Arg99Cys

p.R99C

Q8N6M9

protein_coding

deleterious(0)

probably_damaging(0.915)

TCGA-DF-A2KU-01

Endometrium

uterine corpus endometrioid carcinoma

Female

Unknown

I/II

Unknown

ZFAND2A

insertion

Frame_Shift_Ins

novel

c.129_130insCCAATCAGGAAGGCAGTAAATACGCTTATTGATTTGAATAACTGCA

p.Cys44ProfsTer33

p.C44Pfs*33

Q8N6M9

protein_coding

TCGA-A5-A0GW-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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