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: ANKRD17

Gene summary for ANKRD17

Gene summary.

Gene information	Species	Human
	Gene symbol	ANKRD17
	Gene ID	26057
	Gene name	ankyrin repeat domain 17
	Gene Alias	CAGS
	Cytomap	4q13.3
	Gene Type	protein-coding
	GO ID	GO:0000082
	UniProtAcc	O75179

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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
26057	ANKRD17	CA_HPV_1	Human	Cervix	CC	5.55e-04	-2.80e-02	0.0264
26057	ANKRD17	CCI_1	Human	Cervix	CC	2.06e-10	1.13e+00	0.528
26057	ANKRD17	CCI_2	Human	Cervix	CC	3.66e-13	1.50e+00	0.5249
26057	ANKRD17	CCI_3	Human	Cervix	CC	6.55e-14	1.08e+00	0.516
26057	ANKRD17	HTA11_3410_2000001011	Human	Colorectum	AD	1.21e-13	-4.94e-01	0.0155
26057	ANKRD17	HTA11_347_2000001011	Human	Colorectum	AD	6.30e-14	6.52e-01	-0.1954
26057	ANKRD17	HTA11_1391_2000001011	Human	Colorectum	AD	6.92e-05	4.19e-01	-0.059
26057	ANKRD17	HTA11_99999965062_69753	Human	Colorectum	MSI-H	3.56e-09	7.47e-01	0.3487
26057	ANKRD17	HTA11_99999973899_84307	Human	Colorectum	MSS	1.40e-07	-7.07e-01	0.2585
26057	ANKRD17	HTA11_99999974143_84620	Human	Colorectum	MSS	1.72e-08	-4.13e-01	0.3005
26057	ANKRD17	F007	Human	Colorectum	FAP	2.10e-05	-4.17e-01	0.1176
26057	ANKRD17	A002-C-010	Human	Colorectum	FAP	1.47e-03	-1.92e-01	0.242
26057	ANKRD17	A001-C-207	Human	Colorectum	FAP	2.46e-02	-2.65e-01	0.1278
26057	ANKRD17	A015-C-203	Human	Colorectum	FAP	1.28e-37	-6.50e-01	-0.1294
26057	ANKRD17	A015-C-204	Human	Colorectum	FAP	4.17e-09	-4.89e-01	-0.0228
26057	ANKRD17	A014-C-040	Human	Colorectum	FAP	3.67e-08	-5.69e-01	-0.1184
26057	ANKRD17	A002-C-201	Human	Colorectum	FAP	5.89e-18	-5.14e-01	0.0324
26057	ANKRD17	A001-C-119	Human	Colorectum	FAP	6.95e-08	-4.73e-01	-0.1557
26057	ANKRD17	A001-C-108	Human	Colorectum	FAP	3.81e-16	-4.21e-01	-0.0272
26057	ANKRD17	A002-C-205	Human	Colorectum	FAP	4.10e-33	-5.82e-01	-0.1236

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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
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:0039528	Liver	HCC	cytoplasmic pattern recognition receptor signaling pathway in response to virus	30/7958	34/18723	3.88e-08	8.39e-07	30
GO:00027533	Liver	HCC	cytoplasmic pattern recognition receptor signaling pathway	46/7958	60/18723	7.37e-08	1.49e-06	46
GO:00022211	Liver	HCC	pattern recognition receptor signaling pathway	107/7958	172/18723	1.37e-07	2.58e-06	107
GO:00395291	Liver	HCC	RIG-I signaling pathway	24/7958	27/18723	7.23e-07	1.12e-05	24
GO:00516071	Liver	HCC	defense response to virus	151/7958	265/18723	1.27e-06	1.85e-05	151
GO:01405461	Liver	HCC	defense response to symbiont	151/7958	265/18723	1.27e-06	1.85e-05	151
GO:19019901	Liver	HCC	regulation of mitotic cell cycle phase transition	167/7958	299/18723	1.96e-06	2.71e-05	167
GO:19019871	Liver	HCC	regulation of cell cycle phase transition	211/7958	390/18723	2.11e-06	2.89e-05	211
GO:00985861	Liver	HCC	cellular response to virus	57/7958	84/18723	2.30e-06	3.11e-05	57
GO:004578711	Liver	HCC	positive regulation of cell cycle	172/7958	313/18723	5.29e-06	6.58e-05	172
GO:00062601	Liver	HCC	DNA replication	146/7958	260/18723	5.68e-06	7.02e-05	146
GO:000724912	Liver	HCC	I-kappaB kinase/NF-kappaB signaling	156/7958	281/18723	6.66e-06	8.00e-05	156
GO:004312312	Liver	HCC	positive regulation of I-kappaB kinase/NF-kappaB signaling	108/7958	186/18723	1.28e-05	1.43e-04	108
GO:004312212	Liver	HCC	regulation of I-kappaB kinase/NF-kappaB signaling	138/7958	249/18723	2.47e-05	2.58e-04	138
GO:00448432	Liver	HCC	cell cycle G1/S phase transition	134/7958	241/18723	2.60e-05	2.70e-04	134
GO:0039531	Liver	HCC	regulation of viral-induced cytoplasmic pattern recognition receptor signaling pathway	20/7958	24/18723	4.92e-05	4.70e-04	20
GO:00000822	Liver	HCC	G1/S transition of mitotic cell cycle	119/7958	214/18723	7.11e-05	6.39e-04	119
GO:00028312	Liver	HCC	regulation of response to biotic stimulus	173/7958	327/18723	8.55e-05	7.48e-04	173
GO:00395351	Liver	HCC	regulation of RIG-I signaling pathway	17/7958	20/18723	1.18e-04	9.87e-04	17
GO:00900683	Liver	HCC	positive regulation of cell cycle process	125/7958	236/18723	7.21e-04	4.40e-03	125

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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

ANKRD17

SNV

Missense_Mutation

novel

c.5167N>T

p.Val1723Phe

p.V1723F

O75179

protein_coding

deleterious(0.01)

probably_damaging(0.991)

TCGA-A2-A3Y0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

ANKRD17

SNV

Missense_Mutation

novel

c.259N>A

p.Glu87Lys

p.E87K

O75179

protein_coding

deleterious_low_confidence(0)

benign(0.001)

TCGA-A8-A075-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

epirubicin

ANKRD17

SNV

Missense_Mutation

c.1460T>C

p.Ile487Thr

p.I487T

O75179

protein_coding

deleterious(0.01)

probably_damaging(0.996)

TCGA-A8-A08L-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

ANKRD17

SNV

Missense_Mutation

novel

c.2864N>A

p.Pro955His

p.P955H

O75179

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.533)

TCGA-A8-A08S-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

ANKRD17

SNV

Missense_Mutation

c.427G>A

p.Glu143Lys

p.E143K

O75179

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.503)

TCGA-A8-A09A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

ANKRD17

SNV

Missense_Mutation

c.920C>T

p.Ala307Val

p.A307V

O75179

protein_coding

tolerated(0.09)

probably_damaging(0.968)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ANKRD17

SNV

Missense_Mutation

novel

c.5234G>A

p.Gly1745Asp

p.G1745D

O75179

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ANKRD17

SNV

Missense_Mutation

c.2777N>G

p.Tyr926Cys

p.Y926C

O75179

protein_coding

tolerated_low_confidence(0.15)

benign(0.003)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ANKRD17

SNV

Missense_Mutation

novel

c.3031A>G

p.Met1011Val

p.M1011V

O75179

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.824)

TCGA-AN-A0XU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ANKRD17

SNV

Missense_Mutation

c.1177A>G

p.Ile393Val

p.I393V

O75179

protein_coding

tolerated(0.24)

probably_damaging(0.958)

TCGA-AO-A0J9-01

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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