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: ZFP36

Gene summary for ZFP36

Gene summary.

Gene information	Species	Human
	Gene symbol	ZFP36
	Gene ID	7538
	Gene name	ZFP36 ring finger protein
	Gene Alias	G0S24
	Cytomap	19q13.2
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	M0QY76

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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
7538	ZFP36	GSM4909280	Human	Breast	Precancer	7.69e-15	9.31e-01	0.0305
7538	ZFP36	GSM4909285	Human	Breast	IDC	1.15e-03	3.04e-02	0.21
7538	ZFP36	GSM4909286	Human	Breast	IDC	5.04e-05	-1.92e-01	0.1081
7538	ZFP36	GSM4909288	Human	Breast	IDC	4.83e-03	-6.77e-01	0.0988
7538	ZFP36	GSM4909290	Human	Breast	IDC	6.11e-04	-5.10e-01	0.2096
7538	ZFP36	GSM4909293	Human	Breast	IDC	2.60e-15	-5.72e-01	0.1581
7538	ZFP36	GSM4909294	Human	Breast	IDC	2.29e-28	-7.43e-01	0.2022
7538	ZFP36	GSM4909297	Human	Breast	IDC	5.79e-06	-1.03e-02	0.1517
7538	ZFP36	GSM4909299	Human	Breast	IDC	3.79e-27	6.46e-01	0.035
7538	ZFP36	GSM4909300	Human	Breast	IDC	2.09e-29	8.89e-01	0.0334
7538	ZFP36	GSM4909304	Human	Breast	IDC	1.21e-17	-6.21e-01	0.1636
7538	ZFP36	GSM4909305	Human	Breast	IDC	2.34e-15	5.39e-01	0.0436
7538	ZFP36	GSM4909307	Human	Breast	IDC	6.83e-13	-5.88e-01	0.1569
7538	ZFP36	GSM4909308	Human	Breast	IDC	1.98e-04	2.86e-01	0.158
7538	ZFP36	GSM4909311	Human	Breast	IDC	1.36e-24	-4.16e-01	0.1534
7538	ZFP36	GSM4909312	Human	Breast	IDC	1.55e-11	3.84e-01	0.1552
7538	ZFP36	GSM4909313	Human	Breast	IDC	9.42e-25	6.42e-01	0.0391
7538	ZFP36	GSM4909315	Human	Breast	IDC	1.16e-22	-7.48e-01	0.21
7538	ZFP36	GSM4909316	Human	Breast	IDC	2.35e-08	-8.17e-01	0.21
7538	ZFP36	GSM4909317	Human	Breast	IDC	6.68e-05	-4.90e-01	0.1355

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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
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
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:003166726	Esophagus	HGIN	response to nutrient levels	89/2587	474/18723	1.41e-03	1.64e-02	89
GO:005134827	Esophagus	HGIN	negative regulation of transferase activity	55/2587	268/18723	1.51e-03	1.74e-02	55
GO:007138320	Esophagus	HGIN	cellular response to steroid hormone stimulus	44/2587	204/18723	1.56e-03	1.79e-02	44
GO:004343420	Esophagus	HGIN	response to peptide hormone	79/2587	414/18723	1.60e-03	1.79e-02	79
GO:00459305	Esophagus	HGIN	negative regulation of mitotic cell cycle	49/2587	235/18723	1.88e-03	2.01e-02	49
GO:006115710	Esophagus	HGIN	mRNA destabilization	22/2587	84/18723	1.91e-03	2.03e-02	22
GO:006021115	Esophagus	HGIN	regulation of nuclear-transcribed mRNA poly(A) tail shortening	7/2587	15/18723	2.22e-03	2.28e-02	7
GO:19019915	Esophagus	HGIN	negative regulation of mitotic cell cycle phase transition	39/2587	179/18723	2.31e-03	2.36e-02	39
GO:00190834	Esophagus	HGIN	viral transcription	15/2587	50/18723	2.35e-03	2.39e-02	15
GO:00314404	Esophagus	HGIN	regulation of mRNA 3'-end processing	10/2587	28/18723	3.04e-03	2.88e-02	10
GO:0035019	Esophagus	HGIN	somatic stem cell population maintenance	13/2587	42/18723	3.32e-03	3.12e-02	13
GO:004887227	Esophagus	HGIN	homeostasis of number of cells	54/2587	272/18723	3.50e-03	3.23e-02	54
GO:005077910	Esophagus	HGIN	RNA destabilization	22/2587	88/18723	3.57e-03	3.27e-02	22
GO:190165318	Esophagus	HGIN	cellular response to peptide	68/2587	359/18723	3.88e-03	3.54e-02	68
GO:000028910	Esophagus	HGIN	nuclear-transcribed mRNA poly(A) tail shortening	10/2587	29/18723	4.07e-03	3.65e-02	10
GO:190237314	Esophagus	HGIN	negative regulation of mRNA catabolic process	17/2587	63/18723	4.29e-03	3.82e-02	17
GO:004259418	Esophagus	HGIN	response to starvation	41/2587	197/18723	4.34e-03	3.84e-02	41
GO:00027633	Esophagus	HGIN	positive regulation of myeloid leukocyte differentiation	16/2587	58/18723	4.35e-03	3.84e-02	16
GO:190370620	Esophagus	HGIN	regulation of hemopoiesis	69/2587	367/18723	4.39e-03	3.86e-02	69
GO:00611584	Esophagus	HGIN	3'-UTR-mediated mRNA destabilization	7/2587	17/18723	5.21e-03	4.30e-02	7

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0516718	Breast	Precancer	Kaposi sarcoma-associated herpesvirus infection	36/684	194/8465	1.68e-06	2.53e-05	1.94e-05	36
hsa0516618	Breast	Precancer	Human T-cell leukemia virus 1 infection	33/684	222/8465	4.29e-04	3.31e-03	2.53e-03	33
hsa0516719	Breast	Precancer	Kaposi sarcoma-associated herpesvirus infection	36/684	194/8465	1.68e-06	2.53e-05	1.94e-05	36
hsa0516619	Breast	Precancer	Human T-cell leukemia virus 1 infection	33/684	222/8465	4.29e-04	3.31e-03	2.53e-03	33
hsa0516723	Breast	IDC	Kaposi sarcoma-associated herpesvirus infection	38/867	194/8465	5.87e-05	5.96e-04	4.46e-04	38
hsa0516624	Breast	IDC	Human T-cell leukemia virus 1 infection	40/867	222/8465	2.52e-04	2.21e-03	1.66e-03	40
hsa0516733	Breast	IDC	Kaposi sarcoma-associated herpesvirus infection	38/867	194/8465	5.87e-05	5.96e-04	4.46e-04	38
hsa0516634	Breast	IDC	Human T-cell leukemia virus 1 infection	40/867	222/8465	2.52e-04	2.21e-03	1.66e-03	40
hsa0516743	Breast	DCIS	Kaposi sarcoma-associated herpesvirus infection	38/846	194/8465	3.43e-05	3.69e-04	2.72e-04	38
hsa0516642	Breast	DCIS	Human T-cell leukemia virus 1 infection	41/846	222/8465	7.03e-05	6.88e-04	5.07e-04	41
hsa0516753	Breast	DCIS	Kaposi sarcoma-associated herpesvirus infection	38/846	194/8465	3.43e-05	3.69e-04	2.72e-04	38
hsa0516652	Breast	DCIS	Human T-cell leukemia virus 1 infection	41/846	222/8465	7.03e-05	6.88e-04	5.07e-04	41
hsa0516720	Cervix	CC	Kaposi sarcoma-associated herpesvirus infection	60/1267	194/8465	9.74e-09	1.58e-07	9.33e-08	60
hsa0516620	Cervix	CC	Human T-cell leukemia virus 1 infection	61/1267	222/8465	8.13e-07	7.98e-06	4.72e-06	61
hsa05167110	Cervix	CC	Kaposi sarcoma-associated herpesvirus infection	60/1267	194/8465	9.74e-09	1.58e-07	9.33e-08	60
hsa05166110	Cervix	CC	Human T-cell leukemia virus 1 infection	61/1267	222/8465	8.13e-07	7.98e-06	4.72e-06	61
hsa0516625	Cervix	HSIL_HPV	Human T-cell leukemia virus 1 infection	25/459	222/8465	3.95e-04	3.49e-03	2.82e-03	25
hsa0516635	Cervix	HSIL_HPV	Human T-cell leukemia virus 1 infection	25/459	222/8465	3.95e-04	3.49e-03	2.82e-03	25
hsa05166	Colorectum	AD	Human T-cell leukemia virus 1 infection	72/2092	222/8465	5.24e-03	2.44e-02	1.55e-02	72
hsa051661	Colorectum	AD	Human T-cell leukemia virus 1 infection	72/2092	222/8465	5.24e-03	2.44e-02	1.55e-02	72

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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

ZFP36

SNV

Missense_Mutation

novel

c.669N>G

p.Ser223Arg

p.S223R

protein_coding

tolerated(0.44)

possibly_damaging(0.543)

TCGA-A7-A3IY-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

ZFP36

SNV

Missense_Mutation

c.862N>A

p.Asp288Asn

p.D288N

protein_coding

deleterious(0.04)

possibly_damaging(0.894)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ZFP36

SNV

Missense_Mutation

novel

c.671N>T

p.Ser224Phe

p.S224F

protein_coding

deleterious(0.04)

probably_damaging(1)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ZFP36

SNV

Missense_Mutation

c.553N>T

p.Pro185Ser

p.P185S

protein_coding

tolerated(0.19)

benign(0.138)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ZFP36

SNV

Missense_Mutation

novel

c.66N>G

p.Asp22Glu

p.D22E

protein_coding

tolerated_low_confidence(0.68)

benign(0.01)

TCGA-C5-A1MH-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

ZFP36

SNV

Missense_Mutation

c.122N>T

p.Ser41Leu

p.S41L

protein_coding

tolerated(0.16)

benign(0.165)

TCGA-C5-A1MJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

ZFP36

SNV

Missense_Mutation

c.748N>T

p.Asp250Tyr

p.D250Y

protein_coding

deleterious(0.03)

possibly_damaging(0.847)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ZFP36

SNV

Missense_Mutation

c.97G>C

p.Glu33Gln

p.E33Q

protein_coding

tolerated_low_confidence(0.05)

possibly_damaging(0.897)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

ZFP36

SNV

Missense_Mutation

c.246C>G

p.Phe82Leu

p.F82L

protein_coding

tolerated(0.2)

probably_damaging(0.995)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

ZFP36

SNV

Missense_Mutation

c.553C>T

p.Pro185Ser

p.P185S

protein_coding

tolerated(0.19)

benign(0.138)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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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