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: STRN3

Gene summary for STRN3

Gene summary.

Gene information	Species	Human
	Gene symbol	STRN3
	Gene ID	29966
	Gene name	striatin 3
	Gene Alias	PPP2R6B
	Cytomap	14q12
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	Q13033

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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
29966	STRN3	CCI_1	Human	Cervix	CC	3.41e-06	8.18e-01	0.528
29966	STRN3	CCI_2	Human	Cervix	CC	1.37e-12	1.52e+00	0.5249
29966	STRN3	CCI_3	Human	Cervix	CC	8.29e-05	6.06e-01	0.516
29966	STRN3	HTA11_3410_2000001011	Human	Colorectum	AD	2.37e-20	-6.97e-01	0.0155
29966	STRN3	HTA11_2951_2000001011	Human	Colorectum	AD	2.65e-03	-8.20e-01	0.0216
29966	STRN3	HTA11_3361_2000001011	Human	Colorectum	AD	5.20e-04	-5.30e-01	-0.1207
29966	STRN3	HTA11_83_2000001011	Human	Colorectum	SER	1.08e-03	-3.99e-01	-0.1526
29966	STRN3	HTA11_696_2000001011	Human	Colorectum	AD	3.40e-09	-4.18e-01	-0.1464
29966	STRN3	HTA11_5212_2000001011	Human	Colorectum	AD	2.97e-02	-4.98e-01	-0.2061
29966	STRN3	HTA11_546_2000001011	Human	Colorectum	AD	1.61e-02	-4.39e-01	-0.0842
29966	STRN3	HTA11_7862_2000001011	Human	Colorectum	AD	3.28e-04	-6.15e-01	-0.0179
29966	STRN3	HTA11_866_3004761011	Human	Colorectum	AD	1.62e-10	-5.54e-01	0.096
29966	STRN3	HTA11_8622_2000001021	Human	Colorectum	SER	1.63e-02	-6.53e-01	0.0528
29966	STRN3	HTA11_10623_2000001011	Human	Colorectum	AD	2.25e-02	-5.16e-01	-0.0177
29966	STRN3	HTA11_10711_2000001011	Human	Colorectum	AD	1.32e-10	-6.26e-01	0.0338
29966	STRN3	HTA11_7696_3000711011	Human	Colorectum	AD	9.99e-18	-6.58e-01	0.0674
29966	STRN3	HTA11_6818_2000001021	Human	Colorectum	AD	4.14e-03	-4.60e-01	0.0588
29966	STRN3	HTA11_99999970781_79442	Human	Colorectum	MSS	2.88e-17	-5.18e-01	0.294
29966	STRN3	HTA11_99999971662_82457	Human	Colorectum	MSS	1.74e-22	-6.20e-01	0.3859
29966	STRN3	HTA11_99999973899_84307	Human	Colorectum	MSS	1.14e-07	-6.11e-01	0.2585

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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
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:00097555	Colorectum	CRC	hormone-mediated signaling pathway	46/2078	190/18723	2.28e-07	2.27e-05	46
GO:00305184	Colorectum	CRC	intracellular steroid hormone receptor signaling pathway	32/2078	116/18723	7.37e-07	4.79e-05	32
GO:00485455	Colorectum	CRC	response to steroid hormone	67/2078	339/18723	1.77e-06	8.92e-05	67
GO:00305202	Colorectum	CRC	intracellular estrogen receptor signaling pathway	14/2078	54/18723	1.83e-03	1.87e-02	14
GO:00331444	Colorectum	CRC	negative regulation of intracellular steroid hormone receptor signaling pathway	11/2078	38/18723	2.14e-03	2.10e-02	11
GO:00331432	Colorectum	CRC	regulation of intracellular steroid hormone receptor signaling pathway	17/2078	74/18723	2.61e-03	2.40e-02	17
GO:0032355	Colorectum	CRC	response to estradiol	27/2078	141/18723	3.24e-03	2.81e-02	27
GO:004854516	Endometrium	AEH	response to steroid hormone	76/2100	339/18723	2.15e-09	1.77e-07	76
GO:003052210	Endometrium	AEH	intracellular receptor signaling pathway	60/2100	265/18723	7.16e-08	3.77e-06	60
GO:00323557	Endometrium	AEH	response to estradiol	34/2100	141/18723	1.13e-05	2.53e-04	34
GO:007138310	Endometrium	AEH	cellular response to steroid hormone stimulus	44/2100	204/18723	1.41e-05	3.01e-04	44
GO:00305189	Endometrium	AEH	intracellular steroid hormone receptor signaling pathway	27/2100	116/18723	1.65e-04	2.15e-03	27
GO:00434019	Endometrium	AEH	steroid hormone mediated signaling pathway	29/2100	136/18723	4.71e-04	4.91e-03	29
GO:00097558	Endometrium	AEH	hormone-mediated signaling pathway	37/2100	190/18723	5.64e-04	5.62e-03	37
GO:00331435	Endometrium	AEH	regulation of intracellular steroid hormone receptor signaling pathway	16/2100	74/18723	7.12e-03	4.09e-02	16
GO:00331446	Endometrium	AEH	negative regulation of intracellular steroid hormone receptor signaling pathway	10/2100	38/18723	7.62e-03	4.31e-02	10
GO:003052215	Endometrium	EEC	intracellular receptor signaling pathway	65/2168	265/18723	2.52e-09	1.96e-07	65
GO:004854517	Endometrium	EEC	response to steroid hormone	77/2168	339/18723	3.80e-09	2.71e-07	77
GO:007138315	Endometrium	EEC	cellular response to steroid hormone stimulus	45/2168	204/18723	1.40e-05	2.79e-04	45
GO:003235514	Endometrium	EEC	response to estradiol	34/2168	141/18723	2.22e-05	3.98e-04	34

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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

STRN3

SNV

Missense_Mutation

novel

c.799N>A

p.Glu267Lys

p.E267K

Q13033

protein_coding

tolerated(0.35)

benign(0.105)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

STRN3

insertion

Nonsense_Mutation

novel

c.1399_1400insATCACTAATTTCAGAACATTTCAAACATTCAGAACATT

p.Arg467HisfsTer3

p.R467Hfs*3

Q13033

protein_coding

TCGA-A7-A0CG-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

STRN3

deletion

In_Frame_Del

c.1981_1983delNNN

p.Leu661del

p.L661del

Q13033

protein_coding

TCGA-A8-A093-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

STRN3

SNV

Missense_Mutation

novel

c.1651N>T

p.Gly551Cys

p.G551C

Q13033

protein_coding

deleterious(0.03)

probably_damaging(1)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

STRN3

SNV

Missense_Mutation

novel

c.707N>C

p.Glu236Ala

p.E236A

Q13033

protein_coding

tolerated(0.63)

benign(0)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

STRN3

SNV

Missense_Mutation

rs746673084

c.574N>G

p.Ile192Val

p.I192V

Q13033

protein_coding

tolerated(0.05)

probably_damaging(0.97)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

STRN3

SNV

Missense_Mutation

novel

c.977G>A

p.Gly326Asp

p.G326D

Q13033

protein_coding

tolerated(0.08)

probably_damaging(0.996)

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

STRN3

SNV

Missense_Mutation

novel

c.934G>A

p.Glu312Lys

p.E312K

Q13033

protein_coding

deleterious(0)

probably_damaging(0.956)

TCGA-VS-A958-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

STRN3

SNV

Missense_Mutation

rs774032309

c.1447G>A

p.Val483Ile

p.V483I

Q13033

protein_coding

tolerated(1)

probably_damaging(0.989)

TCGA-A6-5661-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

STRN3

SNV

Missense_Mutation

c.1500N>T

p.Glu500Asp

p.E500D

Q13033

protein_coding

deleterious(0.04)

probably_damaging(0.989)

TCGA-AA-3672-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

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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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