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: PIAS1

Gene summary for PIAS1

Gene summary.

Gene information	Species	Human
	Gene symbol	PIAS1
	Gene ID	8554
	Gene name	protein inhibitor of activated STAT 1
	Gene Alias	DDXBP1
	Cytomap	15q23
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	O75925

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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
8554	PIAS1	CCI_2	Human	Cervix	CC	1.38e-11	1.35e+00	0.5249
8554	PIAS1	CCI_3	Human	Cervix	CC	2.25e-05	7.26e-01	0.516
8554	PIAS1	L1	Human	Cervix	CC	1.18e-02	-1.57e-01	0.0802
8554	PIAS1	HTA11_3410_2000001011	Human	Colorectum	AD	2.64e-14	-4.77e-01	0.0155
8554	PIAS1	HTA11_3361_2000001011	Human	Colorectum	AD	1.99e-02	-4.74e-01	-0.1207
8554	PIAS1	HTA11_866_2000001011	Human	Colorectum	AD	9.34e-04	-3.32e-01	-0.1001
8554	PIAS1	HTA11_866_3004761011	Human	Colorectum	AD	4.48e-08	-4.58e-01	0.096
8554	PIAS1	HTA11_7663_2000001011	Human	Colorectum	SER	7.74e-03	-2.90e-01	0.0131
8554	PIAS1	HTA11_10711_2000001011	Human	Colorectum	AD	3.18e-05	-4.74e-01	0.0338
8554	PIAS1	HTA11_7696_3000711011	Human	Colorectum	AD	1.66e-10	-4.67e-01	0.0674
8554	PIAS1	HTA11_99999970781_79442	Human	Colorectum	MSS	1.08e-07	-3.99e-01	0.294
8554	PIAS1	HTA11_99999971662_82457	Human	Colorectum	MSS	1.21e-09	-5.12e-01	0.3859
8554	PIAS1	HTA11_99999973899_84307	Human	Colorectum	MSS	4.64e-02	-4.93e-01	0.2585
8554	PIAS1	HTA11_99999974143_84620	Human	Colorectum	MSS	2.23e-06	-4.61e-01	0.3005
8554	PIAS1	A001-C-207	Human	Colorectum	FAP	1.69e-03	-2.40e-01	0.1278
8554	PIAS1	A015-C-203	Human	Colorectum	FAP	1.79e-27	-3.88e-01	-0.1294
8554	PIAS1	A015-C-204	Human	Colorectum	FAP	2.01e-07	-3.47e-01	-0.0228
8554	PIAS1	A014-C-040	Human	Colorectum	FAP	2.19e-04	-3.51e-01	-0.1184
8554	PIAS1	A002-C-201	Human	Colorectum	FAP	8.24e-17	-3.59e-01	0.0324
8554	PIAS1	A002-C-203	Human	Colorectum	FAP	4.10e-04	-1.96e-01	0.2786

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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
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
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:004217610	Cervix	CC	regulation of protein catabolic process	104/2311	391/18723	9.39e-15	9.36e-12	104
GO:004586210	Cervix	CC	positive regulation of proteolysis	95/2311	372/18723	1.84e-12	6.86e-10	95
GO:190336210	Cervix	CC	regulation of cellular protein catabolic process	72/2311	255/18723	5.98e-12	2.10e-09	72
GO:004573210	Cervix	CC	positive regulation of protein catabolic process	65/2311	231/18723	7.44e-11	1.39e-08	65
GO:001049810	Cervix	CC	proteasomal protein catabolic process	111/2311	490/18723	8.98e-11	1.58e-08	111
GO:190332010	Cervix	CC	regulation of protein modification by small protein conjugation or removal	66/2311	242/18723	2.31e-10	3.46e-08	66
GO:000989610	Cervix	CC	positive regulation of catabolic process	109/2311	492/18723	5.26e-10	6.99e-08	109
GO:190305010	Cervix	CC	regulation of proteolysis involved in cellular protein catabolic process	60/2311	221/18723	1.82e-09	1.98e-07	60
GO:200005810	Cervix	CC	regulation of ubiquitin-dependent protein catabolic process	47/2311	164/18723	1.63e-08	1.25e-06	47
GO:004316110	Cervix	CC	proteasome-mediated ubiquitin-dependent protein catabolic process	91/2311	412/18723	1.65e-08	1.25e-06	91
GO:003133110	Cervix	CC	positive regulation of cellular catabolic process	91/2311	427/18723	9.64e-08	5.25e-06	91
GO:190336410	Cervix	CC	positive regulation of cellular protein catabolic process	43/2311	155/18723	1.80e-07	8.28e-06	43
GO:00447725	Cervix	CC	mitotic cell cycle phase transition	89/2311	424/18723	2.70e-07	1.12e-05	89
GO:006113610	Cervix	CC	regulation of proteasomal protein catabolic process	48/2311	187/18723	4.63e-07	1.77e-05	48
GO:003243410	Cervix	CC	regulation of proteasomal ubiquitin-dependent protein catabolic process	38/2311	134/18723	4.99e-07	1.88e-05	38
GO:00454445	Cervix	CC	fat cell differentiation	53/2311	229/18723	3.72e-06	9.75e-05	53
GO:00000824	Cervix	CC	G1/S transition of mitotic cell cycle	49/2311	214/18723	1.16e-05	2.48e-04	49
GO:00448434	Cervix	CC	cell cycle G1/S phase transition	53/2311	241/18723	1.76e-05	3.32e-04	53
GO:19030528	Cervix	CC	positive regulation of proteolysis involved in cellular protein catabolic process	34/2311	133/18723	2.28e-05	4.01e-04	34
GO:200006010	Cervix	CC	positive regulation of ubiquitin-dependent protein catabolic process	29/2311	107/18723	2.77e-05	4.62e-04	29

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0412014	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa0412015	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa04120	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa05160	Colorectum	AD	Hepatitis C	54/2092	157/8465	3.87e-03	1.96e-02	1.25e-02	54
hsa041201	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa051601	Colorectum	AD	Hepatitis C	54/2092	157/8465	3.87e-03	1.96e-02	1.25e-02	54
hsa041202	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa041203	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa041204	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa051602	Colorectum	MSS	Hepatitis C	52/1875	157/8465	9.29e-04	5.58e-03	3.42e-03	52
hsa041205	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa051603	Colorectum	MSS	Hepatitis C	52/1875	157/8465	9.29e-04	5.58e-03	3.42e-03	52
hsa041206	Colorectum	FAP	Ubiquitin mediated proteolysis	51/1404	142/8465	1.55e-08	5.84e-07	3.55e-07	51
hsa041207	Colorectum	FAP	Ubiquitin mediated proteolysis	51/1404	142/8465	1.55e-08	5.84e-07	3.55e-07	51
hsa041208	Colorectum	CRC	Ubiquitin mediated proteolysis	42/1091	142/8465	9.98e-08	6.67e-06	4.52e-06	42
hsa041209	Colorectum	CRC	Ubiquitin mediated proteolysis	42/1091	142/8465	9.98e-08	6.67e-06	4.52e-06	42
hsa0412026	Esophagus	HGIN	Ubiquitin mediated proteolysis	49/1383	142/8465	7.78e-08	1.33e-06	1.06e-06	49
hsa04120111	Esophagus	HGIN	Ubiquitin mediated proteolysis	49/1383	142/8465	7.78e-08	1.33e-06	1.06e-06	49
hsa0412027	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa051609	Esophagus	ESCC	Hepatitis C	107/4205	157/8465	1.75e-06	1.08e-05	5.55e-06	107

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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

PIAS1

SNV

Missense_Mutation

novel

c.946N>C

p.Glu316Gln

p.E316Q

O75925

protein_coding

deleterious(0.01)

probably_damaging(0.917)

TCGA-B6-A40B-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PIAS1

SNV

Missense_Mutation

c.1063C>T

p.His355Tyr

p.H355Y

O75925

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PIAS1

SNV

Missense_Mutation

novel

c.97C>A

p.His33Asn

p.H33N

O75925

protein_coding

tolerated(0.07)

benign(0.031)

TCGA-OL-A6VR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PIAS1

insertion

Frame_Shift_Ins

novel

c.1948_1949insATGCTCCCACACATCCTCA

p.Ile650AsnfsTer43

p.I650Nfs*43

O75925

protein_coding

TCGA-A2-A0EO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

PIAS1

insertion

Frame_Shift_Ins

novel

c.1729_1730insATTTTTTTATCTTTTATACCATATT

p.Leu577HisfsTer25

p.L577Hfs*25

O75925

protein_coding

TCGA-AO-A0JD-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

PIAS1

SNV

Missense_Mutation

novel

c.985N>C

p.Thr329Pro

p.T329P

O75925

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PIAS1

SNV

Missense_Mutation

novel

c.569N>G

p.Ser190Cys

p.S190C

O75925

protein_coding

deleterious(0.01)

probably_damaging(0.962)

TCGA-C5-A7X5-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

carboplatin

PIAS1

SNV

Missense_Mutation

c.1250C>T

p.Pro417Leu

p.P417L

O75925

protein_coding

deleterious(0)

possibly_damaging(0.701)

TCGA-A6-2686-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

PIAS1

SNV

Missense_Mutation

c.1372N>G

p.Lys458Glu

p.K458E

O75925

protein_coding

deleterious(0)

benign(0.18)

TCGA-A6-4105-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

PIAS1

SNV

Missense_Mutation

c.85N>A

p.Gly29Arg

p.G29R

O75925

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AA-3947-01

Colorectum

colon adenocarcinoma

Female

<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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