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: SSH1

Gene summary for SSH1

Gene summary.

Gene information	Species	Human
	Gene symbol	SSH1
	Gene ID	54434
	Gene name	slingshot protein phosphatase 1
	Gene Alias	SSH1L
	Cytomap	12q24.11
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	Q8WYL5

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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
54434	SSH1	NAFLD1	Human	Liver	NAFLD	3.85e-02	3.44e-01	-0.04
54434	SSH1	HCC1_Meng	Human	Liver	HCC	3.63e-30	-2.21e-02	0.0246
54434	SSH1	HCC2_Meng	Human	Liver	HCC	4.65e-09	-1.74e-02	0.0107
54434	SSH1	HCC2	Human	Liver	HCC	7.98e-12	3.61e+00	0.5341
54434	SSH1	S027	Human	Liver	HCC	1.41e-13	1.11e+00	0.2446
54434	SSH1	S028	Human	Liver	HCC	6.05e-11	7.05e-01	0.2503
54434	SSH1	S029	Human	Liver	HCC	3.67e-07	5.77e-01	0.2581
54434	SSH1	RNA-P6T1-P6T1-4	Human	Lung	MIAC	8.14e-03	5.74e-01	-0.0263
54434	SSH1	RNA-P6T2-P6T2-3	Human	Lung	IAC	2.62e-02	1.74e-01	-0.013
54434	SSH1	RNA-P7T1-P7T1-4	Human	Lung	AIS	4.19e-05	6.13e-01	-0.0809
54434	SSH1	C04	Human	Oral cavity	OSCC	2.82e-02	2.49e-01	0.2633
54434	SSH1	C21	Human	Oral cavity	OSCC	3.13e-03	1.54e-01	0.2678
54434	SSH1	C30	Human	Oral cavity	OSCC	3.19e-22	8.62e-01	0.3055
54434	SSH1	C43	Human	Oral cavity	OSCC	3.47e-08	1.71e-01	0.1704
54434	SSH1	C51	Human	Oral cavity	OSCC	7.35e-13	4.54e-01	0.2674
54434	SSH1	C06	Human	Oral cavity	OSCC	7.87e-03	5.52e-01	0.2699
54434	SSH1	C07	Human	Oral cavity	OSCC	3.44e-02	3.90e-01	0.2491
54434	SSH1	C09	Human	Oral cavity	OSCC	3.24e-06	1.84e-01	0.1431
54434	SSH1	LN46	Human	Oral cavity	OSCC	3.21e-06	1.89e-01	0.1666
54434	SSH1	EOLP-1	Human	Oral cavity	EOLP	4.59e-14	3.34e-01	-0.0202

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
Liver		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:00070157	Liver	NAFLD	actin filament organization	78/1882	442/18723	5.44e-07	3.21e-05	78
GO:19029037	Liver	NAFLD	regulation of supramolecular fiber organization	66/1882	383/18723	8.97e-06	2.96e-04	66
GO:00163115	Liver	NAFLD	dephosphorylation	69/1882	417/18723	2.27e-05	6.23e-04	69
GO:00329707	Liver	NAFLD	regulation of actin filament-based process	66/1882	397/18723	2.92e-05	7.72e-04	66
GO:00064706	Liver	NAFLD	protein dephosphorylation	50/1882	281/18723	4.53e-05	1.09e-03	50
GO:00329567	Liver	NAFLD	regulation of actin cytoskeleton organization	60/1882	358/18723	5.20e-05	1.20e-03	60
GO:01100537	Liver	NAFLD	regulation of actin filament organization	49/1882	278/18723	6.88e-05	1.46e-03	49
GO:00466837	Liver	NAFLD	response to organophosphorus	28/1882	131/18723	9.05e-05	1.82e-03	28
GO:00432547	Liver	NAFLD	regulation of protein-containing complex assembly	66/1882	428/18723	2.83e-04	4.53e-03	66
GO:00140747	Liver	NAFLD	response to purine-containing compound	29/1882	148/18723	3.34e-04	5.13e-03	29
GO:00512587	Liver	NAFLD	protein polymerization	49/1882	297/18723	3.54e-04	5.36e-03	49
GO:00322717	Liver	NAFLD	regulation of protein polymerization	38/1882	233/18723	1.90e-03	1.93e-02	38
GO:00081547	Liver	NAFLD	actin polymerization or depolymerization	36/1882	218/18723	1.98e-03	1.98e-02	36
GO:00325356	Liver	NAFLD	regulation of cellular component size	55/1882	383/18723	4.31e-03	3.55e-02	55
GO:00300417	Liver	NAFLD	actin filament polymerization	31/1882	191/18723	5.06e-03	3.96e-02	31
GO:00709977	Liver	NAFLD	neuron death	52/1882	361/18723	5.08e-03	3.96e-02	52
GO:0014911	Liver	NAFLD	positive regulation of smooth muscle cell migration	11/1882	47/18723	5.92e-03	4.47e-02	11
GO:0014910	Liver	NAFLD	regulation of smooth muscle cell migration	17/1882	89/18723	6.91e-03	4.87e-02	17
GO:19038297	Liver	NAFLD	positive regulation of cellular protein localization	41/1882	276/18723	7.11e-03	4.95e-02	41
GO:00308337	Liver	NAFLD	regulation of actin filament polymerization	28/1882	172/18723	7.15e-03	4.96e-02	28

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0481010	Liver	NAFLD	Regulation of actin cytoskeleton	50/1043	229/8465	3.01e-05	7.59e-04	6.11e-04	50
hsa0481011	Liver	NAFLD	Regulation of actin cytoskeleton	50/1043	229/8465	3.01e-05	7.59e-04	6.11e-04	50
hsa0481041	Liver	HCC	Regulation of actin cytoskeleton	134/4020	229/8465	4.48e-04	1.94e-03	1.08e-03	134
hsa0481051	Liver	HCC	Regulation of actin cytoskeleton	134/4020	229/8465	4.48e-04	1.94e-03	1.08e-03	134
hsa0481026	Oral cavity	OSCC	Regulation of actin cytoskeleton	129/3704	229/8465	7.14e-05	2.74e-04	1.40e-04	129
hsa0436014	Oral cavity	OSCC	Axon guidance	97/3704	182/8465	5.59e-03	1.33e-02	6.76e-03	97
hsa04810111	Oral cavity	OSCC	Regulation of actin cytoskeleton	129/3704	229/8465	7.14e-05	2.74e-04	1.40e-04	129
hsa0436015	Oral cavity	OSCC	Axon guidance	97/3704	182/8465	5.59e-03	1.33e-02	6.76e-03	97
hsa0481027	Oral cavity	EOLP	Regulation of actin cytoskeleton	50/1218	229/8465	1.34e-03	4.80e-03	2.83e-03	50
hsa0436023	Oral cavity	EOLP	Axon guidance	38/1218	182/8465	1.02e-02	2.80e-02	1.65e-02	38
hsa0481036	Oral cavity	EOLP	Regulation of actin cytoskeleton	50/1218	229/8465	1.34e-03	4.80e-03	2.83e-03	50
hsa0436033	Oral cavity	EOLP	Axon guidance	38/1218	182/8465	1.02e-02	2.80e-02	1.65e-02	38
hsa0481043	Oral cavity	NEOLP	Regulation of actin cytoskeleton	55/1112	229/8465	4.12e-06	3.86e-05	2.42e-05	55
hsa0436041	Oral cavity	NEOLP	Axon guidance	37/1112	182/8465	4.02e-03	1.64e-02	1.03e-02	37
hsa0481053	Oral cavity	NEOLP	Regulation of actin cytoskeleton	55/1112	229/8465	4.12e-06	3.86e-05	2.42e-05	55
hsa0436051	Oral cavity	NEOLP	Axon guidance	37/1112	182/8465	4.02e-03	1.64e-02	1.03e-02	37
hsa0481020	Prostate	BPH	Regulation of actin cytoskeleton	80/1718	229/8465	1.23e-07	1.31e-06	8.10e-07	80
hsa04810110	Prostate	BPH	Regulation of actin cytoskeleton	80/1718	229/8465	1.23e-07	1.31e-06	8.10e-07	80
hsa0481025	Prostate	Tumor	Regulation of actin cytoskeleton	84/1791	229/8465	3.40e-08	4.17e-07	2.58e-07	84
hsa0481035	Prostate	Tumor	Regulation of actin cytoskeleton	84/1791	229/8465	3.40e-08	4.17e-07	2.58e-07	84

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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

SSH1

SNV

Missense_Mutation

c.1652N>G

p.His551Arg

p.H551R

Q8WYL5

protein_coding

tolerated_low_confidence(0.44)

benign(0)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SSH1

SNV

Missense_Mutation

novel

c.2216G>T

p.Ser739Ile

p.S739I

Q8WYL5

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.454)

TCGA-AN-A0FV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SSH1

SNV

Missense_Mutation

rs774943975

c.794N>A

p.Ser265Asn

p.S265N

Q8WYL5

protein_coding

deleterious(0.01)

possibly_damaging(0.588)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

SSH1

SNV

Missense_Mutation

novel

c.2170N>A

p.Asp724Asn

p.D724N

Q8WYL5

protein_coding

deleterious_low_confidence(0.02)

benign(0.056)

TCGA-BH-A0HP-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

SSH1

insertion

Frame_Shift_Ins

novel

c.3074_3075insGCTCCCACCGTGTCTTCAAGAAGAACCATGTTTTAGG

p.Ala1026LeufsTer68

p.A1026Lfs*68

Q8WYL5

protein_coding

TCGA-A2-A0T2-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

xeloda

SSH1

insertion

Nonsense_Mutation

novel

c.1217_1218insTTTTTAAAAC

p.Tyr407PhefsTer2

p.Y407Ffs*2

Q8WYL5

protein_coding

TCGA-A8-A06O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

SSH1

insertion

In_Frame_Ins

novel

c.1215_1216insAACAAAAAT

p.Ile405_Ala406insAsnLysAsn

p.I405_A406insNKN

Q8WYL5

protein_coding

TCGA-A8-A06O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

SSH1

insertion

Frame_Shift_Ins

novel

c.2082_2083insAGGCTTCTGTTCAGTAATGAATCTGAGAA

p.Ala695ArgfsTer50

p.A695Rfs*50

Q8WYL5

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SSH1

insertion

Frame_Shift_Ins

novel

c.2048_2049insC

p.Pro684ThrfsTer80

p.P684Tfs*80

Q8WYL5

protein_coding

TCGA-BH-A0AY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

SSH1

insertion

Nonsense_Mutation

novel

c.2046_2047insATGGCCCTGTAGGAAGAAACTGGGTAAATGTGAAGCC

p.Leu683MetfsTer4

p.L683Mfs*4

Q8WYL5

protein_coding

TCGA-BH-A0AY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

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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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