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:000961518	Esophagus	ESCC	response to virus	238/8552	367/18723	6.65e-14	3.32e-12	238
GO:00482853	Esophagus	ESCC	organelle fission	301/8552	488/18723	4.64e-13	2.12e-11	301
GO:0010821110	Esophagus	ESCC	regulation of mitochondrion organization	107/8552	144/18723	2.31e-12	9.41e-11	107
GO:00516075	Esophagus	ESCC	defense response to virus	171/8552	265/18723	3.91e-10	1.05e-08	171
GO:01405465	Esophagus	ESCC	defense response to symbiont	171/8552	265/18723	3.91e-10	1.05e-08	171
GO:003434013	Esophagus	ESCC	response to type I interferon	48/8552	58/18723	6.18e-09	1.26e-07	48
GO:00603375	Esophagus	ESCC	type I interferon signaling pathway	41/8552	50/18723	1.35e-07	2.17e-06	41
GO:00713575	Esophagus	ESCC	cellular response to type I interferon	42/8552	52/18723	2.15e-07	3.30e-06	42
GO:00028318	Esophagus	ESCC	regulation of response to biotic stimulus	191/8552	327/18723	2.12e-06	2.45e-05	191
GO:00607595	Esophagus	ESCC	regulation of response to cytokine stimulus	103/8552	162/18723	3.14e-06	3.53e-05	103
GO:0043434111	Esophagus	ESCC	response to peptide hormone	234/8552	414/18723	4.93e-06	5.21e-05	234
GO:000283212	Esophagus	ESCC	negative regulation of response to biotic stimulus	72/8552	108/18723	8.36e-06	8.11e-05	72
GO:00019595	Esophagus	ESCC	regulation of cytokine-mediated signaling pathway	95/8552	150/18723	9.48e-06	9.04e-05	95
GO:00603385	Esophagus	ESCC	regulation of type I interferon-mediated signaling pathway	29/8552	36/18723	1.91e-05	1.67e-04	29
GO:00450885	Esophagus	ESCC	regulation of innate immune response	125/8552	218/18723	3.34e-04	1.96e-03	125
GO:00507775	Esophagus	ESCC	negative regulation of immune response	112/8552	194/18723	4.67e-04	2.62e-03	112
GO:000268316	Esophagus	ESCC	negative regulation of immune system process	231/8552	434/18723	8.48e-04	4.36e-03	231
GO:00458245	Esophagus	ESCC	negative regulation of innate immune response	45/8552	71/18723	1.98e-03	8.90e-03	45
GO:00002662	Esophagus	ESCC	mitochondrial fission	28/8552	42/18723	4.90e-03	1.89e-02	28
GO:00603392	Esophagus	ESCC	negative regulation of type I interferon-mediated signaling pathway	15/8552	20/18723	7.60e-03	2.71e-02	15

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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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