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: STAT2

Gene summary for STAT2

Gene summary.

Gene information	Species	Human
	Gene symbol	STAT2
	Gene ID	6773
	Gene name	signal transducer and activator of transcription 2
	Gene Alias	IMD44
	Cytomap	12q13.3
	Gene Type	protein-coding
	GO ID	GO:0000266
	UniProtAcc	P52630

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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
6773	STAT2	LZE4T	Human	Esophagus	ESCC	3.74e-02	8.22e-02	0.0811
6773	STAT2	LZE7T	Human	Esophagus	ESCC	6.19e-06	3.81e-01	0.0667
6773	STAT2	LZE20T	Human	Esophagus	ESCC	6.26e-05	2.12e-01	0.0662
6773	STAT2	LZE24T	Human	Esophagus	ESCC	1.86e-14	5.49e-01	0.0596
6773	STAT2	P1T-E	Human	Esophagus	ESCC	1.03e-12	6.96e-01	0.0875
6773	STAT2	P2T-E	Human	Esophagus	ESCC	1.73e-46	9.65e-01	0.1177
6773	STAT2	P4T-E	Human	Esophagus	ESCC	3.83e-09	2.42e-01	0.1323
6773	STAT2	P5T-E	Human	Esophagus	ESCC	4.93e-15	2.79e-01	0.1327
6773	STAT2	P8T-E	Human	Esophagus	ESCC	8.26e-40	7.25e-01	0.0889
6773	STAT2	P9T-E	Human	Esophagus	ESCC	1.63e-11	3.83e-01	0.1131
6773	STAT2	P10T-E	Human	Esophagus	ESCC	5.03e-14	2.30e-01	0.116
6773	STAT2	P11T-E	Human	Esophagus	ESCC	1.41e-13	7.85e-01	0.1426
6773	STAT2	P12T-E	Human	Esophagus	ESCC	5.53e-27	4.74e-01	0.1122
6773	STAT2	P15T-E	Human	Esophagus	ESCC	1.71e-12	3.96e-01	0.1149
6773	STAT2	P16T-E	Human	Esophagus	ESCC	2.74e-15	2.91e-01	0.1153
6773	STAT2	P17T-E	Human	Esophagus	ESCC	1.17e-03	4.42e-01	0.1278
6773	STAT2	P20T-E	Human	Esophagus	ESCC	8.77e-13	4.57e-01	0.1124
6773	STAT2	P21T-E	Human	Esophagus	ESCC	5.89e-20	3.66e-01	0.1617
6773	STAT2	P22T-E	Human	Esophagus	ESCC	3.61e-17	2.92e-01	0.1236
6773	STAT2	P23T-E	Human	Esophagus	ESCC	3.48e-14	5.08e-01	0.108

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:00603386	Skin	cSCC	regulation of type I interferon-mediated signaling pathway	20/4864	36/18723	1.55e-04	1.36e-03	20
GO:000283122	Skin	cSCC	regulation of response to biotic stimulus	112/4864	327/18723	5.00e-04	3.76e-03	112
GO:00028326	Skin	cSCC	negative regulation of response to biotic stimulus	43/4864	108/18723	1.12e-03	7.36e-03	43
GO:004508812	Skin	cSCC	regulation of innate immune response	75/4864	218/18723	3.40e-03	1.84e-02	75
GO:00603393	Skin	cSCC	negative regulation of type I interferon-mediated signaling pathway	11/4864	20/18723	5.40e-03	2.71e-02	11
GO:00607596	Skin	cSCC	regulation of response to cytokine stimulus	57/4864	162/18723	5.77e-03	2.85e-02	57
GO:00458246	Skin	cSCC	negative regulation of innate immune response	28/4864	71/18723	8.86e-03	4.07e-02	28
GO:0043434113	Thyroid	PTC	response to peptide hormone	188/5968	414/18723	4.13e-09	1.09e-07	188
GO:001082124	Thyroid	PTC	regulation of mitochondrion organization	78/5968	144/18723	2.38e-08	5.43e-07	78
GO:000961520	Thyroid	PTC	response to virus	162/5968	367/18723	4.52e-07	7.41e-06	162
GO:00343408	Thyroid	PTC	response to type I interferon	35/5968	58/18723	7.35e-06	8.60e-05	35
GO:00713577	Thyroid	PTC	cellular response to type I interferon	30/5968	52/18723	1.06e-04	8.56e-04	30
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:00603387	Thyroid	PTC	regulation of type I interferon-mediated signaling pathway	21/5968	36/18723	9.36e-04	5.68e-03	21
GO:00482855	Thyroid	PTC	organelle fission	188/5968	488/18723	9.64e-04	5.77e-03	188
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
GO:00607597	Thyroid	PTC	regulation of response to cytokine stimulus	70/5968	162/18723	1.54e-03	8.58e-03	70
GO:00450887	Thyroid	PTC	regulation of innate immune response	89/5968	218/18723	3.16e-03	1.55e-02	89

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05169210	Esophagus	ESCC	Epstein-Barr virus infection	151/4205	202/8465	1.55e-13	3.45e-12	1.77e-12	151
hsa05167211	Esophagus	ESCC	Kaposi sarcoma-associated herpesvirus infection	136/4205	194/8465	4.28e-09	4.22e-08	2.16e-08	136
hsa0516425	Esophagus	ESCC	Influenza A	122/4205	171/8465	5.01e-09	4.79e-08	2.45e-08	122
hsa0516510	Esophagus	ESCC	Human papillomavirus infection	215/4205	331/8465	7.86e-09	7.12e-08	3.65e-08	215
hsa05171211	Esophagus	ESCC	Coronavirus disease - COVID-19	156/4205	232/8465	3.18e-08	2.68e-07	1.37e-07	156
hsa051609	Esophagus	ESCC	Hepatitis C	107/4205	157/8465	1.75e-06	1.08e-05	5.55e-06	107
hsa051619	Esophagus	ESCC	Hepatitis B	108/4205	162/8465	7.68e-06	4.15e-05	2.12e-05	108
hsa046259	Esophagus	ESCC	C-type lectin receptor signaling pathway	73/4205	104/8465	1.57e-05	7.98e-05	4.09e-05	73
hsa051629	Esophagus	ESCC	Measles	90/4205	139/8465	2.16e-04	7.87e-04	4.03e-04	90
hsa0462122	Esophagus	ESCC	NOD-like receptor signaling pathway	116/4205	186/8465	2.90e-04	1.03e-03	5.30e-04	116
hsa0516937	Esophagus	ESCC	Epstein-Barr virus infection	151/4205	202/8465	1.55e-13	3.45e-12	1.77e-12	151
hsa0516738	Esophagus	ESCC	Kaposi sarcoma-associated herpesvirus infection	136/4205	194/8465	4.28e-09	4.22e-08	2.16e-08	136
hsa0516435	Esophagus	ESCC	Influenza A	122/4205	171/8465	5.01e-09	4.79e-08	2.45e-08	122
hsa0516515	Esophagus	ESCC	Human papillomavirus infection	215/4205	331/8465	7.86e-09	7.12e-08	3.65e-08	215
hsa05171310	Esophagus	ESCC	Coronavirus disease - COVID-19	156/4205	232/8465	3.18e-08	2.68e-07	1.37e-07	156
hsa0516016	Esophagus	ESCC	Hepatitis C	107/4205	157/8465	1.75e-06	1.08e-05	5.55e-06	107
hsa0516114	Esophagus	ESCC	Hepatitis B	108/4205	162/8465	7.68e-06	4.15e-05	2.12e-05	108
hsa0462513	Esophagus	ESCC	C-type lectin receptor signaling pathway	73/4205	104/8465	1.57e-05	7.98e-05	4.09e-05	73
hsa0516213	Esophagus	ESCC	Measles	90/4205	139/8465	2.16e-04	7.87e-04	4.03e-04	90
hsa0462132	Esophagus	ESCC	NOD-like receptor signaling pathway	116/4205	186/8465	2.90e-04	1.03e-03	5.30e-04	116

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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
STAT2	IMENT	Colorectum	Healthy	AL050403.2,SMNDC1,FAM228B, etc.	3.19e-01
STAT2	INCAF	Colorectum	CRC	PARP14,IFI44L,IFI44, etc.	4.73e-01
STAT2	STM	Thyroid	HT	SAMD9L,SAMD9,RSAD2, etc.	6.92e-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

STAT2

SNV

Missense_Mutation

rs755127513

c.2491G>A

p.Glu831Lys

p.E831K

P52630

protein_coding

deleterious_low_confidence(0.01)

benign(0.303)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

STAT2

SNV

Missense_Mutation

c.404N>G

p.Glu135Gly

p.E135G

P52630

protein_coding

tolerated(0.13)

benign(0.054)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

STAT2

SNV

Missense_Mutation

c.2403N>T

p.Glu801Asp

p.E801D

P52630

protein_coding

tolerated_low_confidence(0.25)

benign(0.007)

TCGA-BH-A1FM-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

STAT2

SNV

Missense_Mutation

c.599N>G

p.Gln200Arg

p.Q200R

P52630

protein_coding

tolerated(0.09)

probably_damaging(0.992)

TCGA-C8-A12Z-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

STAT2

SNV

Missense_Mutation

novel

c.2527N>A

p.Asp843Asn

p.D843N

P52630

protein_coding

deleterious_low_confidence(0)

benign(0.104)

TCGA-C8-A8HQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

STAT2

insertion

In_Frame_Ins

novel

c.1120_1121insAAAGGAACAGGGGTTGGG

p.Arg374delinsGlnArgAsnArgGlyTrpGly

p.R374delinsQRNRGWG

P52630

protein_coding

TCGA-A7-A0CE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

STAT2

SNV

Missense_Mutation

novel

c.1063G>A

p.Glu355Lys

p.E355K

P52630

protein_coding

tolerated(0.14)

probably_damaging(0.953)

TCGA-C5-A8XJ-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

STAT2

SNV

Missense_Mutation

c.613G>C

p.Glu205Gln

p.E205Q

P52630

protein_coding

tolerated(0.17)

possibly_damaging(0.889)

TCGA-EK-A2RN-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

STAT2

SNV

Missense_Mutation

c.2348N>T

p.Ser783Leu

p.S783L

P52630

protein_coding

tolerated_low_confidence(0.25)

benign(0.003)

TCGA-EK-A3GK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

STAT2

SNV

Missense_Mutation

c.2309N>C

p.Val770Ala

p.V770A

P52630

protein_coding

tolerated_low_confidence(0.81)

benign(0)

TCGA-HM-A3JK-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
6773	STAT2	TRANSCRIPTION FACTOR, KINASE		13-CIS-RETINOIC ACID		11032398

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