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: SSH2

Gene summary for SSH2

Gene summary.

Gene information	Species	Human
	Gene symbol	SSH2
	Gene ID	85464
	Gene name	slingshot protein phosphatase 2
	Gene Alias	SSH-2
	Cytomap	17q11.2
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	B4DK64

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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
85464	SSH2	CCI_1	Human	Cervix	CC	8.18e-19	1.35e+00	0.528
85464	SSH2	CCI_2	Human	Cervix	CC	2.65e-03	5.11e-01	0.5249
85464	SSH2	CCI_3	Human	Cervix	CC	1.26e-22	1.11e+00	0.516
85464	SSH2	CCII_1	Human	Cervix	CC	1.79e-08	4.03e-01	0.3249
85464	SSH2	HTA11_3410_2000001011	Human	Colorectum	AD	5.09e-07	-4.88e-01	0.0155
85464	SSH2	HTA11_1938_2000001011	Human	Colorectum	AD	1.84e-02	3.57e-01	-0.0811
85464	SSH2	HTA11_347_2000001011	Human	Colorectum	AD	1.83e-14	6.70e-01	-0.1954
85464	SSH2	HTA11_411_2000001011	Human	Colorectum	SER	5.04e-12	8.38e-01	-0.2602
85464	SSH2	HTA11_7862_2000001011	Human	Colorectum	AD	2.33e-02	-4.91e-01	-0.0179
85464	SSH2	HTA11_866_3004761011	Human	Colorectum	AD	4.89e-03	-4.11e-01	0.096
85464	SSH2	HTA11_99999970781_79442	Human	Colorectum	MSS	2.32e-22	-6.65e-01	0.294
85464	SSH2	HTA11_99999974143_84620	Human	Colorectum	MSS	2.08e-03	-3.41e-01	0.3005
85464	SSH2	A001-C-207	Human	Colorectum	FAP	1.17e-02	-3.17e-01	0.1278
85464	SSH2	A015-C-203	Human	Colorectum	FAP	3.55e-33	-5.84e-01	-0.1294
85464	SSH2	A015-C-204	Human	Colorectum	FAP	1.76e-09	-5.28e-01	-0.0228
85464	SSH2	A014-C-040	Human	Colorectum	FAP	2.98e-05	-5.21e-01	-0.1184
85464	SSH2	A002-C-201	Human	Colorectum	FAP	1.12e-10	-4.03e-01	0.0324
85464	SSH2	A001-C-119	Human	Colorectum	FAP	2.77e-08	-5.72e-01	-0.1557
85464	SSH2	A001-C-108	Human	Colorectum	FAP	3.73e-16	-4.68e-01	-0.0272
85464	SSH2	A002-C-205	Human	Colorectum	FAP	2.24e-32	-6.98e-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

∗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:000647022	Lung	AAH	protein dephosphorylation	21/613	281/18723	4.01e-04	1.78e-02	21
GO:011005323	Lung	AAH	regulation of actin filament organization	20/613	278/18723	8.79e-04	2.88e-02	20
GO:005149422	Lung	AAH	negative regulation of cytoskeleton organization	14/613	163/18723	9.62e-04	2.94e-02	14
GO:00353352	Lung	AAH	peptidyl-tyrosine dephosphorylation	10/613	97/18723	1.28e-03	3.52e-02	10
GO:003083313	Lung	AAH	regulation of actin filament polymerization	14/613	172/18723	1.61e-03	3.96e-02	14
GO:003227123	Lung	AAH	regulation of protein polymerization	17/613	233/18723	1.79e-03	4.22e-02	17
GO:000815423	Lung	AAH	actin polymerization or depolymerization	16/613	218/18723	2.27e-03	4.84e-02	16
GO:000701533	Lung	MIAC	actin filament organization	50/967	442/18723	1.64e-07	3.81e-05	50
GO:005125823	Lung	MIAC	protein polymerization	35/967	297/18723	4.69e-06	4.81e-04	35
GO:190290333	Lung	MIAC	regulation of supramolecular fiber organization	41/967	383/18723	8.33e-06	7.24e-04	41
GO:003227132	Lung	MIAC	regulation of protein polymerization	29/967	233/18723	1.06e-05	8.86e-04	29
GO:004325423	Lung	MIAC	regulation of protein-containing complex assembly	44/967	428/18723	1.11e-05	9.00e-04	44
GO:011005332	Lung	MIAC	regulation of actin filament organization	32/967	278/18723	1.91e-05	1.27e-03	32
GO:003297032	Lung	MIAC	regulation of actin filament-based process	41/967	397/18723	1.96e-05	1.28e-03	41
GO:003295632	Lung	MIAC	regulation of actin cytoskeleton organization	37/967	358/18723	4.85e-05	2.49e-03	37
GO:001063922	Lung	MIAC	negative regulation of organelle organization	36/967	348/18723	5.99e-05	2.98e-03	36
GO:005149431	Lung	MIAC	negative regulation of cytoskeleton organization	21/967	163/18723	1.03e-04	4.44e-03	21
GO:190290432	Lung	MIAC	negative regulation of supramolecular fiber organization	19/967	167/18723	1.03e-03	2.10e-02	19
GO:000647031	Lung	MIAC	protein dephosphorylation	27/967	281/18723	1.47e-03	2.55e-02	27
GO:003083323	Lung	MIAC	regulation of actin filament polymerization	19/967	172/18723	1.47e-03	2.55e-02	19

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0481016	Cervix	CC	Regulation of actin cytoskeleton	64/1267	229/8465	2.24e-07	2.59e-06	1.53e-06	64
hsa043609	Cervix	CC	Axon guidance	47/1267	182/8465	8.13e-05	5.38e-04	3.18e-04	47
hsa0481017	Cervix	CC	Regulation of actin cytoskeleton	64/1267	229/8465	2.24e-07	2.59e-06	1.53e-06	64
hsa0436012	Cervix	CC	Axon guidance	47/1267	182/8465	8.13e-05	5.38e-04	3.18e-04	47
hsa04810	Colorectum	AD	Regulation of actin cytoskeleton	75/2092	229/8465	3.36e-03	1.76e-02	1.12e-02	75
hsa04360	Colorectum	AD	Axon guidance	61/2092	182/8465	4.36e-03	2.17e-02	1.38e-02	61
hsa048101	Colorectum	AD	Regulation of actin cytoskeleton	75/2092	229/8465	3.36e-03	1.76e-02	1.12e-02	75
hsa043601	Colorectum	AD	Axon guidance	61/2092	182/8465	4.36e-03	2.17e-02	1.38e-02	61
hsa048102	Colorectum	SER	Regulation of actin cytoskeleton	60/1580	229/8465	2.74e-03	2.02e-02	1.47e-02	60
hsa048103	Colorectum	SER	Regulation of actin cytoskeleton	60/1580	229/8465	2.74e-03	2.02e-02	1.47e-02	60
hsa048104	Colorectum	MSS	Regulation of actin cytoskeleton	68/1875	229/8465	4.27e-03	1.86e-02	1.14e-02	68
hsa043602	Colorectum	MSS	Axon guidance	54/1875	182/8465	1.03e-02	3.69e-02	2.26e-02	54
hsa048105	Colorectum	MSS	Regulation of actin cytoskeleton	68/1875	229/8465	4.27e-03	1.86e-02	1.14e-02	68
hsa043603	Colorectum	MSS	Axon guidance	54/1875	182/8465	1.03e-02	3.69e-02	2.26e-02	54
hsa048106	Colorectum	FAP	Regulation of actin cytoskeleton	65/1404	229/8465	4.07e-06	5.91e-05	3.59e-05	65
hsa043604	Colorectum	FAP	Axon guidance	47/1404	182/8465	9.09e-04	5.20e-03	3.16e-03	47
hsa048107	Colorectum	FAP	Regulation of actin cytoskeleton	65/1404	229/8465	4.07e-06	5.91e-05	3.59e-05	65
hsa043605	Colorectum	FAP	Axon guidance	47/1404	182/8465	9.09e-04	5.20e-03	3.16e-03	47
hsa048108	Colorectum	CRC	Regulation of actin cytoskeleton	52/1091	229/8465	2.34e-05	5.57e-04	3.78e-04	52
hsa043606	Colorectum	CRC	Axon guidance	43/1091	182/8465	4.38e-05	8.70e-04	5.90e-04	43

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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

SSH2

SNV

Missense_Mutation

novel

c.4126N>A

p.Glu1376Lys

p.E1376K

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.737)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

SSH2

SNV

Missense_Mutation

novel

c.343N>T

p.Asp115Tyr

p.D115Y

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-A2-A4S1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SSH2

SNV

Missense_Mutation

c.3790N>C

p.Glu1264Gln

p.E1264Q

protein_coding

deleterious(0.01)

possibly_damaging(0.801)

TCGA-AN-A0XW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

SSH2

SNV

Missense_Mutation

c.2452N>C

p.Glu818Gln

p.E818Q

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.997)

TCGA-AO-A03V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

SSH2

SNV

Missense_Mutation

c.3183G>C

p.Glu1061Asp

p.E1061D

protein_coding

tolerated_low_confidence(0.54)

benign(0.074)

TCGA-C8-A275-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SSH2

SNV

Missense_Mutation

novel

c.989N>A

p.Gly330Asp

p.G330D

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-E9-A3Q9-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cyclophosphane

SSH2

insertion

Frame_Shift_Ins

novel

c.3966_3967insTTTTACTGTTTCT

p.Asp1323PhefsTer5

p.D1323Ffs*5

protein_coding

TCGA-A8-A0A4-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

SSH2

insertion

In_Frame_Ins

novel

c.3964_3965insTATTTTGGT

p.Thr1322delinsIlePheTrpSer

p.T1322delinsIFWS

protein_coding

TCGA-A8-A0A4-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

SSH2

insertion

Frame_Shift_Ins

novel

c.2813_2814insGGAGGCCTTCCCGTGCTACAGACCCAGGGACTGCAGTGTGCATG

p.Gly939GlufsTer34

p.G939Efs*34

protein_coding

TCGA-B6-A0I5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SSH2

deletion

Frame_Shift_Del

novel

c.1929delG

p.Thr644HisfsTer4

p.T644Hfs*4

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

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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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