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: STAT1

Gene summary for STAT1

Gene summary.

Gene information	Species	Human
	Gene symbol	STAT1
	Gene ID	6772
	Gene name	signal transducer and activator of transcription 1
	Gene Alias	CANDF7
	Cytomap	2q32.2
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	P42224

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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
6772	STAT1	GSM4909281	Human	Breast	IDC	7.56e-46	8.44e-01	0.21
6772	STAT1	GSM4909287	Human	Breast	IDC	3.77e-26	7.86e-01	0.2057
6772	STAT1	GSM4909290	Human	Breast	IDC	8.59e-18	6.21e-01	0.2096
6772	STAT1	GSM4909293	Human	Breast	IDC	8.12e-28	5.55e-01	0.1581
6772	STAT1	GSM4909304	Human	Breast	IDC	3.64e-06	3.30e-01	0.1636
6772	STAT1	GSM4909307	Human	Breast	IDC	2.18e-22	5.87e-01	0.1569
6772	STAT1	GSM4909308	Human	Breast	IDC	1.04e-28	6.88e-01	0.158
6772	STAT1	GSM4909309	Human	Breast	IDC	2.37e-04	3.99e-01	0.0483
6772	STAT1	GSM4909317	Human	Breast	IDC	5.48e-09	4.44e-01	0.1355
6772	STAT1	GSM4909319	Human	Breast	IDC	2.30e-05	-9.00e-02	0.1563
6772	STAT1	GSM4909321	Human	Breast	IDC	1.48e-03	2.38e-01	0.1559
6772	STAT1	M1	Human	Breast	IDC	7.08e-04	3.22e-01	0.1577
6772	STAT1	M2	Human	Breast	IDC	3.44e-04	5.62e-01	0.21
6772	STAT1	NCCBC5	Human	Breast	DCIS	7.42e-10	5.10e-01	0.2046
6772	STAT1	P1	Human	Breast	IDC	9.28e-10	4.41e-01	0.1527
6772	STAT1	P2	Human	Breast	IDC	1.05e-32	1.09e+00	0.21
6772	STAT1	P3	Human	Breast	IDC	5.16e-04	6.08e-01	0.1542
6772	STAT1	DCIS2	Human	Breast	DCIS	6.12e-28	1.81e-01	0.0085
6772	STAT1	CA_HPV_1	Human	Cervix	CC	4.59e-47	9.77e-01	0.0264
6772	STAT1	CA_HPV_2	Human	Cervix	CC	2.00e-02	3.85e-01	0.0391

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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:0002262113	Thyroid	PTC	myeloid cell homeostasis	79/5968	157/18723	1.11e-06	1.64e-05	79
GO:000165517	Thyroid	PTC	urogenital system development	149/5968	338/18723	1.41e-06	2.01e-05	149
GO:007200114	Thyroid	PTC	renal system development	135/5968	302/18723	1.76e-06	2.43e-05	135
GO:0030218113	Thyroid	PTC	erythrocyte differentiation	63/5968	120/18723	2.14e-06	2.89e-05	63
GO:00343408	Thyroid	PTC	response to type I interferon	35/5968	58/18723	7.35e-06	8.60e-05	35
GO:0030099113	Thyroid	PTC	myeloid cell differentiation	160/5968	381/18723	1.75e-05	1.82e-04	160
GO:0009612110	Thyroid	PTC	response to mechanical stimulus	98/5968	216/18723	2.09e-05	2.09e-04	98
GO:00324819	Thyroid	PTC	positive regulation of type I interferon production	33/5968	58/18723	7.13e-05	6.19e-04	33
GO:00713577	Thyroid	PTC	cellular response to type I interferon	30/5968	52/18723	1.06e-04	8.56e-04	30
GO:0034612111	Thyroid	PTC	response to tumor necrosis factor	109/5968	253/18723	1.08e-04	8.69e-04	109
GO:00603377	Thyroid	PTC	type I interferon signaling pathway	29/5968	50/18723	1.21e-04	9.66e-04	29
GO:000283114	Thyroid	PTC	regulation of response to biotic stimulus	136/5968	327/18723	1.22e-04	9.69e-04	136
GO:004876215	Thyroid	PTC	mesenchymal cell differentiation	99/5968	236/18723	6.72e-04	4.22e-03	99
GO:0045646111	Thyroid	PTC	regulation of erythrocyte differentiation	26/5968	47/18723	7.38e-04	4.59e-03	26
GO:0071356111	Thyroid	PTC	cellular response to tumor necrosis factor	96/5968	229/18723	8.24e-04	5.10e-03	96
GO:00603338	Thyroid	PTC	interferon-gamma-mediated signaling pathway	17/5968	27/18723	8.67e-04	5.30e-03	17
GO:00324796	Thyroid	PTC	regulation of type I interferon production	45/5968	95/18723	1.13e-03	6.63e-03	45
GO:00326066	Thyroid	PTC	type I interferon production	45/5968	95/18723	1.13e-03	6.63e-03	45
GO:00516077	Thyroid	PTC	defense response to virus	108/5968	265/18723	1.34e-03	7.55e-03	108
GO:01405467	Thyroid	PTC	defense response to symbiont	108/5968	265/18723	1.34e-03	7.55e-03	108

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0517124	Breast	IDC	Coronavirus disease - COVID-19	86/867	232/8465	1.50e-28	9.72e-27	7.27e-27	86
hsa0516922	Breast	IDC	Epstein-Barr virus infection	45/867	202/8465	3.16e-07	6.05e-06	4.52e-06	45
hsa0516723	Breast	IDC	Kaposi sarcoma-associated herpesvirus infection	38/867	194/8465	5.87e-05	5.96e-04	4.46e-04	38
hsa0491916	Breast	IDC	Thyroid hormone signaling pathway	23/867	121/8465	2.45e-03	1.69e-02	1.27e-02	23
hsa0514012	Breast	IDC	Leishmaniasis	16/867	77/8465	4.35e-03	2.57e-02	1.92e-02	16
hsa0517134	Breast	IDC	Coronavirus disease - COVID-19	86/867	232/8465	1.50e-28	9.72e-27	7.27e-27	86
hsa0516932	Breast	IDC	Epstein-Barr virus infection	45/867	202/8465	3.16e-07	6.05e-06	4.52e-06	45
hsa0516733	Breast	IDC	Kaposi sarcoma-associated herpesvirus infection	38/867	194/8465	5.87e-05	5.96e-04	4.46e-04	38
hsa0491917	Breast	IDC	Thyroid hormone signaling pathway	23/867	121/8465	2.45e-03	1.69e-02	1.27e-02	23
hsa0514013	Breast	IDC	Leishmaniasis	16/867	77/8465	4.35e-03	2.57e-02	1.92e-02	16
hsa0516941	Breast	DCIS	Epstein-Barr virus infection	46/846	202/8465	5.60e-08	1.13e-06	8.33e-07	46
hsa0516743	Breast	DCIS	Kaposi sarcoma-associated herpesvirus infection	38/846	194/8465	3.43e-05	3.69e-04	2.72e-04	38
hsa0491922	Breast	DCIS	Thyroid hormone signaling pathway	23/846	121/8465	1.78e-03	1.22e-02	9.00e-03	23
hsa0516951	Breast	DCIS	Epstein-Barr virus infection	46/846	202/8465	5.60e-08	1.13e-06	8.33e-07	46
hsa0516753	Breast	DCIS	Kaposi sarcoma-associated herpesvirus infection	38/846	194/8465	3.43e-05	3.69e-04	2.72e-04	38
hsa0491932	Breast	DCIS	Thyroid hormone signaling pathway	23/846	121/8465	1.78e-03	1.22e-02	9.00e-03	23
hsa0517120	Cervix	CC	Coronavirus disease - COVID-19	111/1267	232/8465	1.82e-33	5.90e-31	3.49e-31	111
hsa0516720	Cervix	CC	Kaposi sarcoma-associated herpesvirus infection	60/1267	194/8465	9.74e-09	1.58e-07	9.33e-08	60
hsa0516920	Cervix	CC	Epstein-Barr virus infection	57/1267	202/8465	7.30e-07	7.39e-06	4.37e-06	57
hsa0514514	Cervix	CC	Toxoplasmosis	34/1267	112/8465	2.42e-05	1.82e-04	1.08e-04	34

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
STAT1	MES	Cervix	ADJ	TAP1,WARS,TAP2, etc.	6.27e-01
STAT1	STM	Cervix	ADJ	TAP1,WARS,TAP2, etc.	1.64e-01
STAT1	MDSC	Lung	Healthy	SLAMF8,IFIT3,GBP1, etc.	8.68e-01

∗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

STAT1

SNV

Missense_Mutation

novel

c.567N>C

p.Lys189Asn

p.K189N

P42224

protein_coding

tolerated(0.43)

benign(0.014)

TCGA-A7-A3IZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

STAT1

SNV

Missense_Mutation

c.1778N>T

p.Asp593Val

p.D593V

P42224

protein_coding

deleterious(0.03)

benign(0.392)

TCGA-D8-A1J8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

nolvadex

STAT1

SNV

Missense_Mutation

c.1236G>C

p.Gln412His

p.Q412H

P42224

protein_coding

deleterious(0)

probably_damaging(0.931)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

STAT1

insertion

Nonsense_Mutation

novel

c.65_66insAGGTT

p.Tyr22Ter

p.Y22*

P42224

protein_coding

TCGA-A8-A09W-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

STAT1

insertion

Frame_Shift_Ins

novel

c.63_64insATCCCCATTTTAAAGATGAGAAAAC

p.Tyr22IlefsTer10

p.Y22Ifs*10

P42224

protein_coding

TCGA-A8-A09W-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

STAT1

insertion

In_Frame_Ins

novel

c.46_47insGCCTGG

p.Leu15_Glu16insGlyLeu

p.L15_E16insGL

P42224

protein_coding

TCGA-BH-A0BG-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

STAT1

SNV

Missense_Mutation

novel

c.431G>T

p.Ser144Ile

p.S144I

P42224

protein_coding

tolerated(0.18)

benign(0.021)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

STAT1

SNV

Missense_Mutation

novel

c.227A>G

p.Asn76Ser

p.N76S

P42224

protein_coding

tolerated(0.13)

benign(0.023)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

STAT1

SNV

Missense_Mutation

c.1035N>C

p.Leu345Phe

p.L345F

P42224

protein_coding

deleterious(0.01)

possibly_damaging(0.629)

TCGA-C5-A1BI-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

STAT1

SNV

Missense_Mutation

c.1945N>T

p.Arg649Cys

p.R649C

P42224

protein_coding

deleterious(0.03)

possibly_damaging(0.48)

TCGA-C5-A1BQ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

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
6772	STAT1	DRUGGABLE GENOME, DRUG RESISTANCE, TRANSCRIPTION FACTOR, KINASE		AVT-02 UE
6772	STAT1	DRUGGABLE GENOME, DRUG RESISTANCE, TRANSCRIPTION FACTOR, KINASE		PMID26394986-Compound-10
6772	STAT1	DRUGGABLE GENOME, DRUG RESISTANCE, TRANSCRIPTION FACTOR, KINASE		Peptidomimetic analog 5
6772	STAT1	DRUGGABLE GENOME, DRUG RESISTANCE, TRANSCRIPTION FACTOR, KINASE		IPRIFLAVONE	IPRIFLAVONE
6772	STAT1	DRUGGABLE GENOME, DRUG RESISTANCE, TRANSCRIPTION FACTOR, KINASE		GARCINOL	GARCINOL
6772	STAT1	DRUGGABLE GENOME, DRUG RESISTANCE, TRANSCRIPTION FACTOR, KINASE		GUTTIFERONE K	GUTTIFERONE K
6772	STAT1	DRUGGABLE GENOME, DRUG RESISTANCE, TRANSCRIPTION FACTOR, KINASE		Peptide analog 8
6772	STAT1	DRUGGABLE GENOME, DRUG RESISTANCE, TRANSCRIPTION FACTOR, KINASE		Platinum IV complexe 1
6772	STAT1	DRUGGABLE GENOME, DRUG RESISTANCE, TRANSCRIPTION FACTOR, KINASE		Oxazole derivative 1
6772	STAT1	DRUGGABLE GENOME, DRUG RESISTANCE, TRANSCRIPTION FACTOR, KINASE		10-METHOXYLRUTAECARPINE	CHEMBL85826

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