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: AKAP9

Gene summary for AKAP9

Gene summary.

Gene information	Species	Human
	Gene symbol	AKAP9
	Gene ID	10142
	Gene name	A-kinase anchoring protein 9
	Gene Alias	AKAP-9
	Cytomap	7q21.2
	Gene Type	protein-coding
	GO ID	GO:0000226
	UniProtAcc	Q5GIA7

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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
10142	AKAP9	GSM4909286	Human	Breast	IDC	4.58e-05	3.51e-01	0.1081
10142	AKAP9	GSM4909288	Human	Breast	IDC	3.82e-02	-3.09e-01	0.0988
10142	AKAP9	GSM4909293	Human	Breast	IDC	6.20e-06	2.30e-01	0.1581
10142	AKAP9	GSM4909294	Human	Breast	IDC	8.99e-04	-2.59e-01	0.2022
10142	AKAP9	GSM4909296	Human	Breast	IDC	1.39e-09	5.14e-02	0.1524
10142	AKAP9	GSM4909297	Human	Breast	IDC	2.55e-17	-2.64e-01	0.1517
10142	AKAP9	GSM4909298	Human	Breast	IDC	4.10e-03	2.75e-01	0.1551
10142	AKAP9	GSM4909301	Human	Breast	IDC	6.65e-21	5.75e-01	0.1577
10142	AKAP9	GSM4909311	Human	Breast	IDC	4.33e-33	-2.98e-01	0.1534
10142	AKAP9	GSM4909312	Human	Breast	IDC	2.21e-10	-1.31e-01	0.1552
10142	AKAP9	GSM4909313	Human	Breast	IDC	1.84e-08	3.39e-01	0.0391
10142	AKAP9	GSM4909315	Human	Breast	IDC	2.38e-10	-3.81e-01	0.21
10142	AKAP9	GSM4909316	Human	Breast	IDC	4.38e-04	-4.89e-01	0.21
10142	AKAP9	GSM4909317	Human	Breast	IDC	1.40e-06	3.66e-01	0.1355
10142	AKAP9	GSM4909319	Human	Breast	IDC	4.44e-41	-2.82e-01	0.1563
10142	AKAP9	GSM4909320	Human	Breast	IDC	7.04e-10	2.18e-01	0.1575
10142	AKAP9	GSM4909321	Human	Breast	IDC	1.22e-17	-2.30e-01	0.1559
10142	AKAP9	M1	Human	Breast	IDC	2.75e-03	3.55e-01	0.1577
10142	AKAP9	NCCBC11	Human	Breast	DCIS	1.88e-03	-8.90e-02	0.1232
10142	AKAP9	NCCBC14	Human	Breast	DCIS	4.13e-13	-1.83e-01	0.2021

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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:190290514	Breast	IDC	positive regulation of supramolecular fiber organization	37/1434	209/18723	1.33e-06	5.75e-05	37
GO:004325414	Breast	IDC	regulation of protein-containing complex assembly	61/1434	428/18723	1.77e-06	7.31e-05	61
GO:003133414	Breast	IDC	positive regulation of protein-containing complex assembly	40/1434	237/18723	1.77e-06	7.31e-05	40
GO:005165114	Breast	IDC	maintenance of location in cell	37/1434	214/18723	2.39e-06	9.35e-05	37
GO:003297014	Breast	IDC	regulation of actin filament-based process	56/1434	397/18723	6.37e-06	1.99e-04	56
GO:190290314	Breast	IDC	regulation of supramolecular fiber organization	54/1434	383/18723	9.40e-06	2.66e-04	54
GO:005123513	Breast	IDC	maintenance of location	48/1434	327/18723	9.90e-06	2.77e-04	48
GO:005159114	Breast	IDC	response to cAMP	20/1434	93/18723	2.00e-05	4.91e-04	20
GO:003227314	Breast	IDC	positive regulation of protein polymerization	25/1434	138/18723	4.46e-05	1.01e-03	25
GO:005149513	Breast	IDC	positive regulation of cytoskeleton organization	35/1434	226/18723	5.04e-05	1.09e-03	35
GO:004668312	Breast	IDC	response to organophosphorus	24/1434	131/18723	5.22e-05	1.12e-03	24
GO:001095913	Breast	IDC	regulation of metal ion transport	52/1434	406/18723	1.76e-04	2.97e-03	52
GO:001407412	Breast	IDC	response to purine-containing compound	24/1434	148/18723	3.65e-04	5.23e-03	24
GO:003241111	Breast	IDC	positive regulation of transporter activity	20/1434	120/18723	7.64e-04	9.27e-03	20
GO:00322719	Breast	IDC	regulation of protein polymerization	32/1434	233/18723	9.19e-04	1.05e-02	32
GO:00432703	Breast	IDC	positive regulation of ion transport	36/1434	275/18723	1.11e-03	1.22e-02	36
GO:00512589	Breast	IDC	protein polymerization	38/1434	297/18723	1.26e-03	1.34e-02	38
GO:002289812	Breast	IDC	regulation of transmembrane transporter activity	36/1434	278/18723	1.35e-03	1.40e-02	36
GO:003241411	Breast	IDC	positive regulation of ion transmembrane transporter activity	18/1434	109/18723	1.53e-03	1.53e-02	18
GO:003476711	Breast	IDC	positive regulation of ion transmembrane transport	24/1434	167/18723	2.07e-03	1.95e-02	24

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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

AKAP9

SNV

Missense_Mutation

c.5677N>G

p.Leu1893Val

p.L1893V

Q99996

protein_coding

tolerated(0.08)

benign(0.162)

TCGA-A2-A04P-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxol

AKAP9

SNV

Missense_Mutation

c.5825N>T

p.Thr1942Ile

p.T1942I

Q99996

protein_coding

tolerated(0.3)

benign(0)

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

AKAP9

SNV

Missense_Mutation

c.10727N>A

p.Ser3576Tyr

p.S3576Y

Q99996

protein_coding

tolerated(0.56)

benign(0.007)

TCGA-A2-A0YM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

AKAP9

SNV

Missense_Mutation

novel

c.9220G>C

p.Glu3074Gln

p.E3074Q

Q99996

protein_coding

tolerated(0.55)

benign(0.067)

TCGA-A7-A5ZW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

AKAP9

SNV

Missense_Mutation

c.938A>T

p.Asp313Val

p.D313V

Q99996

protein_coding

tolerated(0.07)

benign(0.154)

TCGA-A8-A06T-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

AKAP9

SNV

Missense_Mutation

c.3185N>A

p.Gly1062Glu

p.G1062E

Q99996

protein_coding

tolerated(0.85)

benign(0)

TCGA-A8-A092-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

AKAP9

SNV

Missense_Mutation

c.7369N>A

p.His2457Asn

p.H2457N

Q99996

protein_coding

tolerated(0.31)

benign(0)

TCGA-A8-A0A7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

AKAP9

SNV

Missense_Mutation

c.5839N>T

p.Arg1947Cys

p.R1947C

Q99996

protein_coding

deleterious(0)

probably_damaging(0.951)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

AKAP9

SNV

Missense_Mutation

rs745335257

c.11617N>A

p.Asp3873Asn

p.D3873N

Q99996

protein_coding

deleterious(0)

probably_damaging(0.961)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

AKAP9

SNV

Missense_Mutation

novel

c.4243N>A

p.Glu1415Lys

p.E1415K

Q99996

protein_coding

tolerated(0.17)

benign(0.061)

TCGA-AC-A3BB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

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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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