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: ATF7

Gene summary for ATF7

Gene summary.

Gene information	Species	Human
	Gene symbol	ATF7
	Gene ID	11016
	Gene name	activating transcription factor 7
	Gene Alias	ATFA
	Cytomap	12q13.13
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	P17544

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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
11016	ATF7	HTA12-26-1	Human	Pancreas	PDAC	9.58e-10	4.87e-01	0.3728
11016	ATF7	HTA12-29-1	Human	Pancreas	PDAC	1.72e-23	5.20e-01	0.3722
11016	ATF7	male-WTA	Human	Thyroid	PTC	2.07e-14	1.43e-01	0.1037
11016	ATF7	PTC01	Human	Thyroid	PTC	4.46e-10	3.80e-02	0.1899
11016	ATF7	PTC04	Human	Thyroid	PTC	1.95e-19	1.57e-01	0.1927
11016	ATF7	PTC05	Human	Thyroid	PTC	1.03e-06	2.69e-01	0.2065
11016	ATF7	PTC06	Human	Thyroid	PTC	1.94e-11	2.83e-01	0.2057
11016	ATF7	PTC07	Human	Thyroid	PTC	2.81e-21	1.71e-01	0.2044
11016	ATF7	ATC09	Human	Thyroid	ATC	2.08e-02	7.68e-02	0.2871
11016	ATF7	ATC12	Human	Thyroid	ATC	6.79e-23	1.37e-01	0.34
11016	ATF7	ATC13	Human	Thyroid	ATC	2.15e-33	6.39e-01	0.34
11016	ATF7	ATC2	Human	Thyroid	ATC	3.26e-06	3.19e-01	0.34
11016	ATF7	ATC4	Human	Thyroid	ATC	2.11e-16	2.01e-01	0.34
11016	ATF7	ATC5	Human	Thyroid	ATC	2.63e-37	6.96e-01	0.34

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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
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
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:004325410	Cervix	CC	regulation of protein-containing complex assembly	96/2311	428/18723	2.91e-09	3.05e-07	96
GO:003164710	Cervix	CC	regulation of protein stability	63/2311	298/18723	1.14e-05	2.45e-04	63
GO:00063257	Cervix	CC	chromatin organization	78/2311	409/18723	5.40e-05	8.02e-04	78
GO:005082110	Cervix	CC	protein stabilization	43/2311	191/18723	5.90e-05	8.54e-04	43
GO:0031647111	Esophagus	ESCC	regulation of protein stability	223/8552	298/18723	5.76e-25	1.52e-22	223
GO:003304416	Esophagus	ESCC	regulation of chromosome organization	145/8552	187/18723	3.80e-19	4.31e-17	145
GO:0043254111	Esophagus	ESCC	regulation of protein-containing complex assembly	278/8552	428/18723	3.81e-16	2.77e-14	278
GO:0050821111	Esophagus	ESCC	protein stabilization	140/8552	191/18723	6.50e-15	3.61e-13	140
GO:00434143	Esophagus	ESCC	macromolecule methylation	199/8552	316/18723	3.44e-10	9.57e-09	199
GO:200125219	Esophagus	ESCC	positive regulation of chromosome organization	64/8552	82/18723	1.98e-09	4.52e-08	64
GO:00322592	Esophagus	ESCC	methylation	222/8552	364/18723	2.26e-09	5.09e-08	222
GO:000632517	Esophagus	ESCC	chromatin organization	240/8552	409/18723	6.52e-08	1.14e-06	240
GO:00400295	Esophagus	ESCC	regulation of gene expression, epigenetic	74/8552	105/18723	2.24e-07	3.42e-06	74
GO:00063673	Esophagus	ESCC	transcription initiation from RNA polymerase II promoter	56/8552	77/18723	1.30e-06	1.59e-05	56
GO:000635211	Esophagus	ESCC	DNA-templated transcription, initiation	86/8552	130/18723	1.88e-06	2.19e-05	86
GO:00708973	Esophagus	ESCC	transcription preinitiation complex assembly	30/8552	36/18723	3.60e-06	3.95e-05	30
GO:00602603	Esophagus	ESCC	regulation of transcription initiation from RNA polymerase II promoter	25/8552	33/18723	4.30e-04	2.43e-03	25
GO:200014212	Esophagus	ESCC	regulation of DNA-templated transcription, initiation	29/8552	40/18723	5.32e-04	2.93e-03	29
GO:00708281	Esophagus	ESCC	heterochromatin organization	31/8552	46/18723	2.42e-03	1.06e-02	31
GO:00511232	Esophagus	ESCC	RNA polymerase II preinitiation complex assembly	18/8552	24/18723	3.43e-03	1.41e-02	18

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
ATF7	MSC	Esophagus	Healthy	MAP2,ZNF554,NCK1-AS1, etc.	9.64e-03
ATF7	CD8TEFF	Prostate	ADJ	DCAF17,VSIG10,NFYA, etc.	2.58e-02

∗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

ATF7

SNV

Missense_Mutation

rs754866750

c.733A>C

p.Ile245Leu

p.I245L

P17544

protein_coding

tolerated(0.66)

benign(0)

TCGA-A2-A1G4-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

adriamycin

ATF7

SNV

Missense_Mutation

rs754866750

c.733N>C

p.Ile245Leu

p.I245L

P17544

protein_coding

tolerated(0.66)

benign(0)

TCGA-AN-A0XR-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

ATF7

SNV

Missense_Mutation

rs754866750

c.733A>C

p.Ile245Leu

p.I245L

P17544

protein_coding

tolerated(0.66)

benign(0)

TCGA-B6-A1KN-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

ATF7

SNV

Missense_Mutation

rs764112606

c.896N>C

p.His299Pro

p.H299P

P17544

protein_coding

deleterious(0.03)

benign(0.133)

TCGA-BH-A0B7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

ATF7

SNV

Missense_Mutation

rs754866750

c.733A>C

p.Ile245Leu

p.I245L

P17544

protein_coding

tolerated(0.66)

benign(0)

TCGA-BH-A1FH-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

ATF7

SNV

Missense_Mutation

rs754866750

c.733A>C

p.Ile245Leu

p.I245L

P17544

protein_coding

tolerated(0.66)

benign(0)

TCGA-C8-A273-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

ATF7

SNV

Missense_Mutation

rs754866750

c.733N>C

p.Ile245Leu

p.I245L

P17544

protein_coding

tolerated(0.66)

benign(0)

TCGA-D8-A1JK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ATF7

SNV

Missense_Mutation

rs754866750

c.733A>C

p.Ile245Leu

p.I245L

P17544

protein_coding

tolerated(0.66)

benign(0)

TCGA-D8-A1JT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

ATF7

SNV

Missense_Mutation

rs754866750

c.733A>C

p.Ile245Leu

p.I245L

P17544

protein_coding

tolerated(0.66)

benign(0)

TCGA-D8-A1XG-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

ATF7

SNV

Missense_Mutation

c.61N>C

p.Glu21Gln

p.E21Q

P17544

protein_coding

deleterious(0)

probably_damaging(0.983)

TCGA-E2-A1L7-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

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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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