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: SKP1

Gene summary for SKP1

Gene summary.

Gene information	Species	Human
	Gene symbol	SKP1
	Gene ID	6500
	Gene name	S-phase kinase associated protein 1
	Gene Alias	EMC19
	Cytomap	5q31.1
	Gene Type	protein-coding
	GO ID	GO:0000209
	UniProtAcc	P63208

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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
6500	SKP1	GSM5353225_PA_PR5196-1_Pool_1_2_3_S53_L002	Human	Prostate	Tumor	9.07e-03	-5.08e-01	0.1619
6500	SKP1	GSM5353226_PA_PR5196-2_Pool_1_2_3_S54_L002	Human	Prostate	Tumor	3.18e-03	-6.92e-01	0.159
6500	SKP1	GSM5353227_PA_PR5199-193K_Pool_1_2_3_S55_L002	Human	Prostate	Tumor	2.02e-10	-6.02e-01	0.1602
6500	SKP1	GSM5353228_PA_PR5199-640K_Pool_1_3_S108_L004	Human	Prostate	Tumor	1.24e-06	-7.61e-01	0.1537
6500	SKP1	GSM5353232_PA_PR5249_T1_S3_L001	Human	Prostate	Tumor	2.32e-07	-7.47e-01	0.1439
6500	SKP1	GSM5353236_PA_PR5251_T1_S7_L001	Human	Prostate	Tumor	3.47e-04	-5.61e-01	0.1608
6500	SKP1	GSM5353240_PA_PR5254_T1_S15_L001	Human	Prostate	Tumor	4.79e-22	-7.05e-01	0.1575
6500	SKP1	GSM5353243_PA_PR5261_T1_S23_L002	Human	Prostate	Tumor	1.42e-30	-6.73e-01	0.1545
6500	SKP1	GSM5353244_PA_PR5261_T2_S24_L002	Human	Prostate	Tumor	3.56e-26	-8.05e-01	0.1569
6500	SKP1	GSM5353247_PA_PR5269_3_S27_L002	Human	Prostate	Tumor	3.08e-03	-8.20e-01	0.1532
6500	SKP1	GSM5353248_PA_PR5269_4_S28_L002	Human	Prostate	Tumor	4.32e-05	-8.58e-01	0.1541
6500	SKP1	P1_S1_AK	Human	Skin	AK	3.46e-08	-8.15e-02	-0.3399
6500	SKP1	P2_S3_AK	Human	Skin	AK	5.51e-08	-1.37e-01	-0.3287
6500	SKP1	P4_S8_cSCC	Human	Skin	cSCC	2.88e-13	2.10e-02	-0.3095
6500	SKP1	P5_S10_cSCC	Human	Skin	cSCC	2.05e-23	-2.11e-01	-0.299
6500	SKP1	P1_cSCC	Human	Skin	cSCC	3.11e-59	2.00e+00	0.0292
6500	SKP1	P2_cSCC	Human	Skin	cSCC	6.23e-53	1.55e+00	-0.024
6500	SKP1	P4_cSCC	Human	Skin	cSCC	4.86e-50	1.54e+00	-0.00290000000000005
6500	SKP1	P10_cSCC	Human	Skin	cSCC	9.92e-69	2.40e+00	0.1017
6500	SKP1	cSCC_p1	Human	Skin	cSCC	2.99e-03	1.50e-01	-0.1916

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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
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
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:19033209	Breast	Precancer	regulation of protein modification by small protein conjugation or removal	38/1080	242/18723	1.71e-08	1.17e-06	38
GO:00313969	Breast	Precancer	regulation of protein ubiquitination	33/1080	210/18723	1.45e-07	7.82e-06	33
GO:00104989	Breast	Precancer	proteasomal protein catabolic process	58/1080	490/18723	1.54e-07	8.05e-06	58
GO:00451859	Breast	Precancer	maintenance of protein location	19/1080	94/18723	1.43e-06	5.35e-05	19
GO:00512358	Breast	Precancer	maintenance of location	40/1080	327/18723	5.85e-06	1.71e-04	40
GO:00516519	Breast	Precancer	maintenance of location in cell	30/1080	214/18723	5.91e-06	1.71e-04	30
GO:00325076	Breast	Precancer	maintenance of protein location in cell	14/1080	65/18723	1.59e-05	3.89e-04	14
GO:00725954	Breast	Precancer	maintenance of protein localization in organelle	10/1080	42/18723	1.06e-04	1.93e-03	10
GO:19046668	Breast	Precancer	regulation of ubiquitin protein ligase activity	7/1080	23/18723	2.26e-04	3.42e-03	7
GO:00431619	Breast	Precancer	proteasome-mediated ubiquitin-dependent protein catabolic process	42/1080	412/18723	2.49e-04	3.72e-03	42
GO:00514386	Breast	Precancer	regulation of ubiquitin-protein transferase activity	10/1080	53/18723	7.88e-04	9.29e-03	10
GO:001049814	Breast	IDC	proteasomal protein catabolic process	75/1434	490/18723	5.59e-09	4.41e-07	75
GO:190332014	Breast	IDC	regulation of protein modification by small protein conjugation or removal	43/1434	242/18723	1.71e-07	9.16e-06	43
GO:003139614	Breast	IDC	regulation of protein ubiquitination	37/1434	210/18723	1.50e-06	6.36e-05	37
GO:005165114	Breast	IDC	maintenance of location in cell	37/1434	214/18723	2.39e-06	9.35e-05	37
GO:004518514	Breast	IDC	maintenance of protein location	21/1434	94/18723	6.69e-06	2.05e-04	21
GO:004316114	Breast	IDC	proteasome-mediated ubiquitin-dependent protein catabolic process	57/1434	412/18723	9.55e-06	2.68e-04	57
GO:005123513	Breast	IDC	maintenance of location	48/1434	327/18723	9.90e-06	2.77e-04	48
GO:003250714	Breast	IDC	maintenance of protein location in cell	16/1434	65/18723	2.29e-05	5.51e-04	16
GO:007259512	Breast	IDC	maintenance of protein localization in organelle	12/1434	42/18723	4.94e-05	1.08e-03	12

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0513218	Breast	Precancer	Salmonella infection	49/684	249/8465	2.92e-09	6.15e-08	4.71e-08	49
hsa0513118	Breast	Precancer	Shigellosis	44/684	247/8465	3.91e-07	6.86e-06	5.26e-06	44
hsa0414118	Breast	Precancer	Protein processing in endoplasmic reticulum	33/684	174/8465	2.78e-06	3.83e-05	2.94e-05	33
hsa0513219	Breast	Precancer	Salmonella infection	49/684	249/8465	2.92e-09	6.15e-08	4.71e-08	49
hsa0513119	Breast	Precancer	Shigellosis	44/684	247/8465	3.91e-07	6.86e-06	5.26e-06	44
hsa0414119	Breast	Precancer	Protein processing in endoplasmic reticulum	33/684	174/8465	2.78e-06	3.83e-05	2.94e-05	33
hsa0513224	Breast	IDC	Salmonella infection	55/867	249/8465	2.07e-08	4.49e-07	3.36e-07	55
hsa0513124	Breast	IDC	Shigellosis	47/867	247/8465	1.78e-05	2.00e-04	1.49e-04	47
hsa0414124	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36
hsa0517014	Breast	IDC	Human immunodeficiency virus 1 infection	33/867	212/8465	9.28e-03	4.37e-02	3.27e-02	33
hsa0513234	Breast	IDC	Salmonella infection	55/867	249/8465	2.07e-08	4.49e-07	3.36e-07	55
hsa0513134	Breast	IDC	Shigellosis	47/867	247/8465	1.78e-05	2.00e-04	1.49e-04	47
hsa0414134	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36
hsa0517015	Breast	IDC	Human immunodeficiency virus 1 infection	33/867	212/8465	9.28e-03	4.37e-02	3.27e-02	33
hsa0513243	Breast	DCIS	Salmonella infection	55/846	249/8465	8.71e-09	1.87e-07	1.38e-07	55
hsa0414143	Breast	DCIS	Protein processing in endoplasmic reticulum	36/846	174/8465	1.60e-05	1.91e-04	1.41e-04	36
hsa0513144	Breast	DCIS	Shigellosis	46/846	247/8465	2.06e-05	2.38e-04	1.75e-04	46
hsa0517024	Breast	DCIS	Human immunodeficiency virus 1 infection	33/846	212/8465	6.49e-03	3.22e-02	2.37e-02	33
hsa0513253	Breast	DCIS	Salmonella infection	55/846	249/8465	8.71e-09	1.87e-07	1.38e-07	55
hsa0414153	Breast	DCIS	Protein processing in endoplasmic reticulum	36/846	174/8465	1.60e-05	1.91e-04	1.41e-04	36

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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

SKP1

SNV

Missense_Mutation

novel

c.228G>C

p.Glu76Asp

p.E76D

P63208

protein_coding

tolerated(0.54)

benign(0.005)

TCGA-AN-A0XW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

SKP1

SNV

Missense_Mutation

novel

c.411N>T

p.Lys137Asn

p.K137N

P63208

protein_coding

deleterious(0.04)

benign(0.158)

TCGA-AA-3877-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

SKP1

SNV

Missense_Mutation

novel

c.407G>C

p.Arg136Pro

p.R136P

P63208

protein_coding

deleterious(0.01)

benign(0.012)

TCGA-AM-5820-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

SKP1

SNV

Missense_Mutation

novel

c.406N>T

p.Arg136Cys

p.R136C

P63208

protein_coding

deleterious(0.04)

benign(0.011)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

SKP1

SNV

Missense_Mutation

novel

c.382N>C

p.Lys128Gln

p.K128Q

P63208

protein_coding

deleterious(0)

possibly_damaging(0.656)

TCGA-D1-A1O8-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

SKP1

insertion

Frame_Shift_Ins

novel

c.226_227insCATCTTTATTATCTTTGCGTATAGCAATTCGTATTATTGGGCAAGAC

p.Glu76AlafsTer34

p.E76Afs*34

P63208

protein_coding

TCGA-DD-A73E-01

Liver

liver hepatocellular carcinoma

Male

>=65

I/II

Unknown

SKP1

SNV

Missense_Mutation

c.49N>T

p.Asp17Tyr

p.D17Y

P63208

protein_coding

deleterious(0)

possibly_damaging(0.891)

TCGA-05-4382-01

Lung

lung adenocarcinoma

Male

>=65

I/II

Unknown

SKP1

SNV

Missense_Mutation

novel

c.239A>G

p.Lys80Arg

p.K80R

P63208

protein_coding

tolerated(0.27)

possibly_damaging(0.899)

TCGA-05-4427-01

Lung

lung adenocarcinoma

Female

>=65

I/II

Chemotherapy

cisplatin

SKP1

SNV

Missense_Mutation

novel

c.139N>G

p.Leu47Val

p.L47V

P63208

protein_coding

tolerated(0.11)

probably_damaging(0.959)

TCGA-49-6742-01

Lung

lung adenocarcinoma

Male

>=65

I/II

Chemotherapy

alimta

SKP1

SNV

Missense_Mutation

novel

c.317N>G

p.Ala106Gly

p.A106G

P63208

protein_coding

deleterious(0)

possibly_damaging(0.698)

TCGA-55-8089-01

Lung

lung adenocarcinoma

Male

<65

I/II

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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