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: KANK1

Gene summary for KANK1

Gene summary.

Gene information	Species	Human
	Gene symbol	KANK1
	Gene ID	23189
	Gene name	KN motif and ankyrin repeat domains 1
	Gene Alias	ANKRD15
	Cytomap	9p24.3
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	Q14678

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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
23189	KANK1	CCI_2	Human	Cervix	CC	8.90e-11	1.13e+00	0.5249
23189	KANK1	CCI_3	Human	Cervix	CC	2.38e-25	1.33e+00	0.516
23189	KANK1	HTA11_347_2000001011	Human	Colorectum	AD	1.57e-03	3.92e-01	-0.1954
23189	KANK1	HTA11_1391_2000001011	Human	Colorectum	AD	1.25e-03	5.77e-01	-0.059
23189	KANK1	HTA11_4255_2000001011	Human	Colorectum	SER	3.34e-05	5.61e-01	0.0446
23189	KANK1	HTA11_7663_2000001011	Human	Colorectum	SER	3.01e-04	6.80e-01	0.0131
23189	KANK1	HTA11_7469_2000001011	Human	Colorectum	AD	6.36e-03	-8.09e-01	-0.0124
23189	KANK1	HTA11_99999965062_69753	Human	Colorectum	MSI-H	1.60e-32	1.49e+00	0.3487
23189	KANK1	HTA11_99999965104_69814	Human	Colorectum	MSS	2.50e-22	1.27e+00	0.281
23189	KANK1	HTA11_99999971662_82457	Human	Colorectum	MSS	5.62e-07	7.93e-01	0.3859
23189	KANK1	A001-C-207	Human	Colorectum	FAP	7.96e-04	1.90e-01	0.1278
23189	KANK1	A015-C-203	Human	Colorectum	FAP	1.76e-13	-1.94e-01	-0.1294
23189	KANK1	A002-C-201	Human	Colorectum	FAP	6.82e-03	-1.92e-01	0.0324
23189	KANK1	A001-C-108	Human	Colorectum	FAP	2.04e-05	-2.42e-03	-0.0272
23189	KANK1	A002-C-205	Human	Colorectum	FAP	8.13e-14	-3.16e-01	-0.1236
23189	KANK1	A001-C-104	Human	Colorectum	FAP	4.15e-04	6.19e-02	0.0184
23189	KANK1	A015-C-006	Human	Colorectum	FAP	3.77e-12	-3.73e-01	-0.0994
23189	KANK1	A015-C-106	Human	Colorectum	FAP	6.23e-05	3.59e-02	-0.0511
23189	KANK1	A002-C-114	Human	Colorectum	FAP	4.40e-15	-5.33e-01	-0.1561
23189	KANK1	A015-C-104	Human	Colorectum	FAP	1.74e-20	-2.60e-01	-0.1899

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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
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
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:00308379	Endometrium	AEH	negative regulation of actin filament polymerization	16/2100	65/18723	1.81e-03	1.44e-02	16
GO:00328699	Endometrium	AEH	cellular response to insulin stimulus	37/2100	203/18723	1.97e-03	1.54e-02	37
GO:00975818	Endometrium	AEH	lamellipodium organization	20/2100	90/18723	2.01e-03	1.56e-02	20
GO:00713758	Endometrium	AEH	cellular response to peptide hormone stimulus	49/2100	290/18723	2.24e-03	1.72e-02	49
GO:00107713	Endometrium	AEH	negative regulation of cell morphogenesis involved in differentiation	6/2100	14/18723	2.67e-03	1.94e-02	6
GO:19000253	Endometrium	AEH	negative regulation of substrate adhesion-dependent cell spreading	6/2100	14/18723	2.67e-03	1.94e-02	6
GO:01200329	Endometrium	AEH	regulation of plasma membrane bounded cell projection assembly	34/2100	186/18723	2.79e-03	2.01e-02	34
GO:00604918	Endometrium	AEH	regulation of cell projection assembly	34/2100	188/18723	3.33e-03	2.32e-02	34
GO:00082866	Endometrium	AEH	insulin receptor signaling pathway	23/2100	116/18723	4.58e-03	2.95e-02	23
GO:00328689	Endometrium	AEH	response to insulin	44/2100	264/18723	4.70e-03	3.00e-02	44
GO:19030369	Endometrium	AEH	positive regulation of response to wounding	16/2100	72/18723	5.40e-03	3.36e-02	16
GO:00071627	Endometrium	AEH	negative regulation of cell adhesion	49/2100	303/18723	5.43e-03	3.37e-02	49
GO:00350236	Endometrium	AEH	regulation of Rho protein signal transduction	18/2100	86/18723	6.39e-03	3.79e-02	18
GO:00108123	Endometrium	AEH	negative regulation of cell-substrate adhesion	15/2100	68/18723	7.45e-03	4.23e-02	15
GO:001081016	Endometrium	EEC	regulation of cell-substrate adhesion	63/2168	221/18723	5.17e-12	8.85e-10	63
GO:002260416	Endometrium	EEC	regulation of cell morphogenesis	78/2168	309/18723	1.45e-11	2.28e-09	78
GO:003158915	Endometrium	EEC	cell-substrate adhesion	87/2168	363/18723	1.95e-11	3.00e-09	87
GO:190002415	Endometrium	EEC	regulation of substrate adhesion-dependent cell spreading	26/2168	57/18723	1.30e-10	1.53e-08	26
GO:003297017	Endometrium	EEC	regulation of actin filament-based process	89/2168	397/18723	4.76e-10	4.76e-08	89
GO:004206017	Endometrium	EEC	wound healing	92/2168	422/18723	1.12e-09	9.58e-08	92

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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

KANK1

SNV

Missense_Mutation

rs761714605

c.2255N>T

p.Ser752Leu

p.S752L

Q14678

protein_coding

deleterious(0.01)

benign(0.219)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

KANK1

SNV

Missense_Mutation

rs775231755

c.3806N>T

p.Thr1269Met

p.T1269M

Q14678

protein_coding

deleterious(0)

probably_damaging(0.989)

TCGA-AC-A62V-01

Breast

breast invasive carcinoma

Male

<65

III/IV

Targeted Molecular therapy

denosumab

KANK1

SNV

Missense_Mutation

novel

c.2756N>T

p.Ser919Ile

p.S919I

Q14678

protein_coding

tolerated(0.2)

benign(0.08)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

KANK1

SNV

Missense_Mutation

c.2482N>C

p.Glu828Gln

p.E828Q

Q14678

protein_coding

tolerated(0.08)

probably_damaging(0.981)

TCGA-AO-A03O-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

KANK1

SNV

Missense_Mutation

novel

c.3775N>A

p.Asp1259Asn

p.D1259N

Q14678

protein_coding

deleterious(0.04)

possibly_damaging(0.737)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

KANK1

SNV

Missense_Mutation

novel

c.2071N>T

p.Leu691Phe

p.L691F

Q14678

protein_coding

tolerated(0.41)

benign(0.003)

TCGA-BH-A0E1-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

KANK1

SNV

Missense_Mutation

novel

c.847N>G

p.Thr283Ala

p.T283A

Q14678

protein_coding

tolerated(0.09)

probably_damaging(0.917)

TCGA-BH-A0HA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

KANK1

SNV

Missense_Mutation

c.3232N>A

p.Glu1078Lys

p.E1078K

Q14678

protein_coding

deleterious(0.04)

benign(0.147)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

KANK1

SNV

Missense_Mutation

novel

c.908C>T

p.Ser303Leu

p.S303L

Q14678

protein_coding

deleterious(0.03)

benign(0.005)

TCGA-E2-A2P6-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

KANK1

SNV

Missense_Mutation

novel

c.1960G>A

p.Ala654Thr

p.A654T

Q14678

protein_coding

tolerated(0.62)

benign(0)

TCGA-OL-A5RW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

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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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