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: SKIL

Gene summary for SKIL

Gene summary.

Gene information	Species	Human
	Gene symbol	SKIL
	Gene ID	6498
	Gene name	SKI like proto-oncogene
	Gene Alias	SNO
	Cytomap	3q26.2
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P12757

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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
6498	SKIL	CA_HPV_1	Human	Cervix	CC	9.80e-04	-4.88e-03	0.0264
6498	SKIL	CA_HPV_2	Human	Cervix	CC	3.15e-10	4.68e-01	0.0391
6498	SKIL	CCI_2	Human	Cervix	CC	1.53e-05	1.00e+00	0.5249
6498	SKIL	CCI_3	Human	Cervix	CC	2.96e-02	6.09e-01	0.516
6498	SKIL	sample3	Human	Cervix	CC	6.55e-04	1.45e-01	0.1387
6498	SKIL	T1	Human	Cervix	CC	1.95e-02	3.38e-01	0.0918
6498	SKIL	T3	Human	Cervix	CC	1.55e-03	1.18e-01	0.1389
6498	SKIL	HTA11_1938_2000001011	Human	Colorectum	AD	1.02e-05	6.34e-01	-0.0811
6498	SKIL	A015-C-203	Human	Colorectum	FAP	1.41e-02	6.94e-02	-0.1294
6498	SKIL	A001-C-108	Human	Colorectum	FAP	1.16e-06	4.15e-01	-0.0272
6498	SKIL	A002-C-205	Human	Colorectum	FAP	5.32e-07	2.60e-01	-0.1236
6498	SKIL	A001-C-104	Human	Colorectum	FAP	8.10e-13	5.40e-01	0.0184
6498	SKIL	A002-C-114	Human	Colorectum	FAP	5.06e-04	2.04e-01	-0.1561
6498	SKIL	A015-C-104	Human	Colorectum	FAP	2.94e-06	1.65e-01	-0.1899
6498	SKIL	A001-C-014	Human	Colorectum	FAP	3.35e-06	4.55e-01	0.0135
6498	SKIL	A002-C-016	Human	Colorectum	FAP	3.57e-06	2.55e-01	0.0521
6498	SKIL	A001-C-203	Human	Colorectum	FAP	6.20e-07	4.85e-01	-0.0481
6498	SKIL	A002-C-116	Human	Colorectum	FAP	9.79e-12	4.25e-01	-0.0452
6498	SKIL	A014-C-008	Human	Colorectum	FAP	8.44e-03	2.12e-01	-0.191
6498	SKIL	A018-E-020	Human	Colorectum	FAP	2.12e-03	1.44e-01	-0.2034

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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:009719122	Liver	HCC	extrinsic apoptotic signaling pathway	143/7958	219/18723	6.99e-12	2.97e-10	143
GO:200124212	Liver	HCC	regulation of intrinsic apoptotic signaling pathway	109/7958	164/18723	4.52e-10	1.45e-08	109
GO:200123621	Liver	HCC	regulation of extrinsic apoptotic signaling pathway	98/7958	151/18723	2.17e-08	5.08e-07	98
GO:000170111	Liver	HCC	in utero embryonic development	204/7958	367/18723	2.44e-07	4.30e-06	204
GO:200102021	Liver	HCC	regulation of response to DNA damage stimulus	128/7958	219/18723	1.31e-06	1.90e-05	128
GO:003134611	Liver	HCC	positive regulation of cell projection organization	193/7958	353/18723	2.28e-06	3.08e-05	193
GO:200123522	Liver	HCC	positive regulation of apoptotic signaling pathway	79/7958	126/18723	3.70e-06	4.82e-05	79
GO:000862511	Liver	HCC	extrinsic apoptotic signaling pathway via death domain receptors	55/7958	82/18723	5.97e-06	7.35e-05	55
GO:007155921	Liver	HCC	response to transforming growth factor beta	141/7958	256/18723	3.08e-05	3.16e-04	141
GO:007156021	Liver	HCC	cellular response to transforming growth factor beta stimulus	137/7958	250/18723	5.47e-05	5.14e-04	137
GO:004887222	Liver	HCC	homeostasis of number of cells	147/7958	272/18723	7.48e-05	6.70e-04	147
GO:200102211	Liver	HCC	positive regulation of response to DNA damage stimulus	64/7958	105/18723	1.03e-04	8.88e-04	64
GO:190204111	Liver	HCC	regulation of extrinsic apoptotic signaling pathway via death domain receptors	34/7958	49/18723	1.28e-04	1.06e-03	34
GO:200123811	Liver	HCC	positive regulation of extrinsic apoptotic signaling pathway	33/7958	48/18723	2.12e-04	1.63e-03	33
GO:200124421	Liver	HCC	positive regulation of intrinsic apoptotic signaling pathway	38/7958	58/18723	3.37e-04	2.36e-03	38
GO:00018251	Liver	HCC	blastocyst formation	27/7958	38/18723	3.47e-04	2.42e-03	27
GO:001072011	Liver	HCC	positive regulation of cell development	155/7958	298/18723	5.39e-04	3.48e-03	155
GO:000863011	Liver	HCC	intrinsic apoptotic signaling pathway in response to DNA damage	58/7958	99/18723	8.97e-04	5.29e-03	58
GO:000717921	Liver	HCC	transforming growth factor beta receptor signaling pathway	106/7958	198/18723	1.09e-03	6.23e-03	106
GO:001097511	Liver	HCC	regulation of neuron projection development	220/7958	445/18723	1.68e-03	8.78e-03	220

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa043504	Endometrium	AEH	TGF-beta signaling pathway	26/1197	108/8465	3.82e-03	2.18e-02	1.59e-02	26
hsa0435011	Endometrium	AEH	TGF-beta signaling pathway	26/1197	108/8465	3.82e-03	2.18e-02	1.59e-02	26
hsa043502	Endometrium	EEC	TGF-beta signaling pathway	26/1237	108/8465	5.95e-03	3.12e-02	2.33e-02	26
hsa043503	Endometrium	EEC	TGF-beta signaling pathway	26/1237	108/8465	5.95e-03	3.12e-02	2.33e-02	26
hsa043507	Esophagus	ESCC	TGF-beta signaling pathway	69/4205	108/8465	1.92e-03	5.54e-03	2.84e-03	69
hsa0435014	Esophagus	ESCC	TGF-beta signaling pathway	69/4205	108/8465	1.92e-03	5.54e-03	2.84e-03	69
hsa043506	Oral cavity	OSCC	TGF-beta signaling pathway	60/3704	108/8465	8.66e-03	1.97e-02	1.00e-02	60
hsa0435013	Oral cavity	OSCC	TGF-beta signaling pathway	60/3704	108/8465	8.66e-03	1.97e-02	1.00e-02	60
hsa0435022	Oral cavity	EOLP	TGF-beta signaling pathway	29/1218	108/8465	4.81e-04	1.92e-03	1.13e-03	29
hsa0435032	Oral cavity	EOLP	TGF-beta signaling pathway	29/1218	108/8465	4.81e-04	1.92e-03	1.13e-03	29
hsa0435041	Oral cavity	NEOLP	TGF-beta signaling pathway	28/1112	108/8465	2.46e-04	1.62e-03	1.02e-03	28
hsa0435051	Oral cavity	NEOLP	TGF-beta signaling pathway	28/1112	108/8465	2.46e-04	1.62e-03	1.02e-03	28
hsa043505	Prostate	BPH	TGF-beta signaling pathway	35/1718	108/8465	1.98e-03	7.92e-03	4.90e-03	35
hsa0435012	Prostate	BPH	TGF-beta signaling pathway	35/1718	108/8465	1.98e-03	7.92e-03	4.90e-03	35
hsa0435021	Prostate	Tumor	TGF-beta signaling pathway	39/1791	108/8465	2.33e-04	1.35e-03	8.39e-04	39
hsa0435031	Prostate	Tumor	TGF-beta signaling pathway	39/1791	108/8465	2.33e-04	1.35e-03	8.39e-04	39

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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

SKIL

SNV

Missense_Mutation

novel

c.656N>T

p.Gly219Val

p.G219V

P12757

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A7-A4SD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

SKIL

SNV

Missense_Mutation

c.805C>G

p.Leu269Val

p.L269V

P12757

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-AR-A24Z-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

SKIL

SNV

Missense_Mutation

rs752596617

c.641N>G

p.Asn214Ser

p.N214S

P12757

protein_coding

tolerated(0.37)

probably_damaging(0.993)

TCGA-BH-A0H7-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

SKIL

SNV

Missense_Mutation

c.567A>T

p.Glu189Asp

p.E189D

P12757

protein_coding

tolerated(0.16)

benign(0.006)

TCGA-BH-A1FU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SKIL

insertion

In_Frame_Ins

novel

c.676_677insTCGCCTACTGTATTTCTGCCTCTTCCATCACCT

p.Ala226delinsValAlaTyrCysIleSerAlaSerSerIleThrSer

p.A226delinsVAYCISASSITS

P12757

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SKIL

insertion

Nonsense_Mutation

novel

c.1165_1166insACTGTAGGGATAGGGTATAGTCTAGCCGA

p.Val389AspfsTer7

p.V389Dfs*7

P12757

protein_coding

TCGA-A8-A095-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

SKIL

deletion

Frame_Shift_Del

novel

c.910delN

p.Val304Ter

p.V304*

P12757

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

SKIL

SNV

Missense_Mutation

novel

c.916C>T

p.His306Tyr

p.H306Y

P12757

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SKIL

SNV

Missense_Mutation

novel

c.1911G>T

p.Arg637Ser

p.R637S

P12757

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SKIL

SNV

Missense_Mutation

c.472C>G

p.Gln158Glu

p.Q158E

P12757

protein_coding

tolerated(0.15)

benign(0.231)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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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