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: IL1B

Gene summary for IL1B

Gene summary.

Gene information	Species	Human
	Gene symbol	IL1B
	Gene ID	3553
	Gene name	interleukin 1 beta
	Gene Alias	IL-1
	Cytomap	2q14.1
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P01584

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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
3553	IL1B	LZE24T	Human	Esophagus	ESCC	2.37e-02	-8.50e-02	0.0596
3553	IL1B	P5T-E	Human	Esophagus	ESCC	2.88e-17	9.39e-01	0.1327
3553	IL1B	P11T-E	Human	Esophagus	ESCC	1.15e-05	1.15e+00	0.1426
3553	IL1B	P21T-E	Human	Esophagus	ESCC	2.10e-13	1.12e+00	0.1617
3553	IL1B	P38T-E	Human	Esophagus	ESCC	4.43e-06	1.46e+00	0.127
3553	IL1B	P47T-E	Human	Esophagus	ESCC	1.83e-07	4.18e-01	0.1067
3553	IL1B	P89T-E	Human	Esophagus	ESCC	4.52e-19	3.63e+00	0.1752
3553	IL1B	P130T-E	Human	Esophagus	ESCC	1.01e-36	2.56e+00	0.1676
3553	IL1B	C04	Human	Oral cavity	OSCC	4.22e-10	2.13e+00	0.2633
3553	IL1B	C21	Human	Oral cavity	OSCC	2.18e-60	2.83e+00	0.2678
3553	IL1B	C30	Human	Oral cavity	OSCC	7.86e-32	1.39e+00	0.3055
3553	IL1B	C43	Human	Oral cavity	OSCC	2.50e-02	4.06e-01	0.1704
3553	IL1B	C51	Human	Oral cavity	OSCC	3.82e-14	4.84e-01	0.2674
3553	IL1B	C57	Human	Oral cavity	OSCC	8.32e-08	4.99e-01	0.1679
3553	IL1B	C06	Human	Oral cavity	OSCC	2.94e-06	1.59e+00	0.2699
3553	IL1B	C07	Human	Oral cavity	OSCC	7.37e-05	7.16e-01	0.2491
3553	IL1B	C08	Human	Oral cavity	OSCC	2.91e-08	3.52e-01	0.1919
3553	IL1B	C09	Human	Oral cavity	OSCC	4.96e-02	3.10e-02	0.1431
3553	IL1B	PTCwithHT_1	Human	Thyroid	HT	5.71e-22	1.41e+00	0.0238
3553	IL1B	PTCwithHT_8	Human	Thyroid	HT	4.31e-16	8.93e-01	0.0351

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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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:0006913110	Esophagus	ESCC	nucleocytoplasmic transport	230/8552	301/18723	6.04e-28	2.02e-25	230
GO:0051169110	Esophagus	ESCC	nuclear transport	230/8552	301/18723	6.04e-28	2.02e-25	230
GO:001657015	Esophagus	ESCC	histone modification	323/8552	463/18723	2.61e-26	7.88e-24	323
GO:014001414	Esophagus	ESCC	mitotic nuclear division	218/8552	287/18723	6.17e-26	1.78e-23	218
GO:0042176111	Esophagus	ESCC	regulation of protein catabolic process	280/8552	391/18723	8.65e-26	2.39e-23	280
GO:2001233111	Esophagus	ESCC	regulation of apoptotic signaling pathway	256/8552	356/18723	4.11e-24	1.04e-21	256
GO:003238618	Esophagus	ESCC	regulation of intracellular transport	243/8552	337/18723	3.20e-23	7.25e-21	243
GO:0009896111	Esophagus	ESCC	positive regulation of catabolic process	332/8552	492/18723	4.36e-23	9.22e-21	332
GO:0031331111	Esophagus	ESCC	positive regulation of cellular catabolic process	292/8552	427/18723	8.67e-22	1.53e-19	292
GO:0051168110	Esophagus	ESCC	nuclear export	126/8552	154/18723	1.88e-20	2.65e-18	126
GO:001820514	Esophagus	ESCC	peptidyl-lysine modification	259/8552	376/18723	3.90e-20	5.26e-18	259
GO:0045862111	Esophagus	ESCC	positive regulation of proteolysis	256/8552	372/18723	7.88e-20	9.43e-18	256
GO:0033157110	Esophagus	ESCC	regulation of intracellular protein transport	169/8552	229/18723	3.31e-18	3.23e-16	169
GO:0032388110	Esophagus	ESCC	positive regulation of intracellular transport	152/8552	202/18723	7.89e-18	7.36e-16	152
GO:0045732111	Esophagus	ESCC	positive regulation of protein catabolic process	167/8552	231/18723	1.47e-16	1.14e-14	167
GO:0097191111	Esophagus	ESCC	extrinsic apoptotic signaling pathway	159/8552	219/18723	4.12e-16	2.94e-14	159
GO:000734615	Esophagus	ESCC	regulation of mitotic cell cycle	293/8552	457/18723	8.00e-16	5.64e-14	293
GO:1904951111	Esophagus	ESCC	positive regulation of establishment of protein localization	216/8552	319/18723	1.01e-15	6.86e-14	216
GO:2001234111	Esophagus	ESCC	negative regulation of apoptotic signaling pathway	161/8552	224/18723	1.24e-15	8.09e-14	161
GO:0046822110	Esophagus	ESCC	regulation of nucleocytoplasmic transport	88/8552	106/18723	1.88e-15	1.19e-13	88

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05132211	Esophagus	ESCC	Salmonella infection	191/4205	249/8465	6.51e-19	5.45e-17	2.79e-17	191
hsa05022210	Esophagus	ESCC	Pathways of neurodegeneration - multiple diseases	318/4205	476/8465	6.10e-15	2.04e-13	1.05e-13	318
hsa05010210	Esophagus	ESCC	Alzheimer disease	263/4205	384/8465	1.80e-14	5.47e-13	2.80e-13	263
hsa04932210	Esophagus	ESCC	Non-alcoholic fatty liver disease	122/4205	155/8465	5.69e-14	1.59e-12	8.14e-13	122
hsa05020210	Esophagus	ESCC	Prion disease	193/4205	273/8465	6.42e-13	1.34e-11	6.89e-12	193
hsa05418211	Esophagus	ESCC	Fluid shear stress and atherosclerosis	109/4205	139/8465	2.00e-12	3.72e-11	1.90e-11	109
hsa05131211	Esophagus	ESCC	Shigellosis	176/4205	247/8465	2.27e-12	4.01e-11	2.05e-11	176
hsa05130211	Esophagus	ESCC	Pathogenic Escherichia coli infection	142/4205	197/8465	8.21e-11	1.06e-09	5.42e-10	142
hsa0466810	Esophagus	ESCC	TNF signaling pathway	89/4205	114/8465	3.36e-10	4.01e-09	2.06e-09	89
hsa0516425	Esophagus	ESCC	Influenza A	122/4205	171/8465	5.01e-09	4.79e-08	2.45e-08	122
hsa0513526	Esophagus	ESCC	Yersinia infection	100/4205	137/8465	1.80e-08	1.59e-07	8.12e-08	100
hsa05171211	Esophagus	ESCC	Coronavirus disease - COVID-19	156/4205	232/8465	3.18e-08	2.68e-07	1.37e-07	156
hsa05417211	Esophagus	ESCC	Lipid and atherosclerosis	143/4205	215/8465	3.30e-07	2.45e-06	1.26e-06	143
hsa05163210	Esophagus	ESCC	Human cytomegalovirus infection	148/4205	225/8465	5.73e-07	4.00e-06	2.05e-06	148
hsa0493310	Esophagus	ESCC	AGE-RAGE signaling pathway in diabetic complications	72/4205	100/8465	4.15e-06	2.28e-05	1.17e-05	72
hsa046259	Esophagus	ESCC	C-type lectin receptor signaling pathway	73/4205	104/8465	1.57e-05	7.98e-05	4.09e-05	73
hsa0465727	Esophagus	ESCC	IL-17 signaling pathway	66/4205	94/8465	3.93e-05	1.75e-04	8.99e-05	66
hsa0513428	Esophagus	ESCC	Legionellosis	42/4205	57/8465	1.83e-04	6.90e-04	3.53e-04	42
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

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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
IL1B	IL1R1_IL1RAP	IL1B_IL1R1_IL1RAP	IL1	Breast	DCIS
IL1B	IL1R2	IL1B_IL1R2	IL1	Breast	DCIS
IL1B	IL1R2	IL1B_IL1R2	IL1	Cervix	ADJ
IL1B	IL1R1_IL1RAP	IL1B_IL1R1_IL1RAP	IL1	Cervix	CC
IL1B	IL1R2	IL1B_IL1R2	IL1	CRC	MSI-H
IL1B	IL1R2	IL1B_IL1R2	IL1	CRC	MSS
IL1B	IL1R2	IL1B_IL1R2	IL1	Endometrium	AEH
IL1B	IL1R2	IL1B_IL1R2	IL1	Endometrium	EEC
IL1B	IL1R2	IL1B_IL1R2	IL1	Esophagus	Healthy
IL1B	IL1R2	IL1B_IL1R2	IL1	GC	ADJ
IL1B	IL1R2	IL1B_IL1R2	IL1	GC	GC
IL1B	IL1R2	IL1B_IL1R2	IL1	HNSCC	ADJ
IL1B	IL1R2	IL1B_IL1R2	IL1	HNSCC	Healthy
IL1B	IL1R2	IL1B_IL1R2	IL1	HNSCC	OSCC
IL1B	IL1R1_IL1RAP	IL1B_IL1R1_IL1RAP	IL1	HNSCC	Precancer
IL1B	IL1R2	IL1B_IL1R2	IL1	HNSCC	Precancer
IL1B	IL1R1_IL1RAP	IL1B_IL1R1_IL1RAP	IL1	Liver	Healthy
IL1B	IL1R1_IL1RAP	IL1B_IL1R1_IL1RAP	IL1	Liver	Precancer
IL1B	IL1R2	IL1B_IL1R2	IL1	Lung	AAH
IL1B	IL1R2	IL1B_IL1R2	IL1	Lung	ADJ

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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

IL1B

SNV

Missense_Mutation

c.33N>T

p.Met11Ile

p.M11I

P01584

protein_coding

tolerated(0.17)

benign(0.026)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

IL1B

SNV

Missense_Mutation

rs766684369

c.374C>T

p.Thr125Met

p.T125M

P01584

protein_coding

tolerated(0.06)

probably_damaging(0.984)

TCGA-CK-5916-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

IL1B

SNV

Missense_Mutation

c.738N>A

p.Met246Ile

p.M246I

P01584

protein_coding

tolerated(0.07)

benign(0.154)

TCGA-D5-6928-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

IL1B

SNV

Missense_Mutation

rs762704392

c.22N>A

p.Ala8Thr

p.A8T

P01584

protein_coding

tolerated(1)

benign(0.001)

TCGA-G4-6309-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Chemotherapy

xeloda

IL1B

SNV

Missense_Mutation

rs144433180

c.562N>A

p.Val188Met

p.V188M

P01584

protein_coding

deleterious(0.02)

possibly_damaging(0.646)

TCGA-WS-AB45-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

IL1B

SNV

Missense_Mutation

novel

c.261N>T

p.Glu87Asp

p.E87D

P01584

protein_coding

tolerated(1)

benign(0)

TCGA-A5-A2K5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

IL1B

SNV

Missense_Mutation

rs755957216

c.193N>A

p.Ala65Thr

p.A65T

P01584

protein_coding

deleterious(0.01)

benign(0.081)

TCGA-AJ-A3BH-01

Endometrium

uterine corpus endometrioid carcinoma

Female

Unknown

I/II

Unknown

IL1B

SNV

Missense_Mutation

novel

c.734N>G

p.Asn245Ser

p.N245S

P01584

protein_coding

tolerated(0.49)

benign(0)

TCGA-AJ-A3EL-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

IL1B

SNV

Missense_Mutation

rs144640380

c.423N>C

p.Glu141Asp

p.E141D

P01584

protein_coding

tolerated(0.05)

possibly_damaging(0.641)

TCGA-AJ-A3EL-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

IL1B

SNV

Missense_Mutation

rs775562734

c.152N>A

p.Arg51Gln

p.R51Q

P01584

protein_coding

tolerated(1)

benign(0.001)

TCGA-AJ-A3EL-01

Endometrium

uterine corpus endometrioid carcinoma

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
3553	IL1B	KINASE, DRUGGABLE GENOME		VERAPAMIL	VERAPAMIL	2686646
3553	IL1B	KINASE, DRUGGABLE GENOME		ERYTHROMYCIN	ERYTHROMYCIN	2534682
3553	IL1B	KINASE, DRUGGABLE GENOME		BECLOMETHASONE DIPROPIONATE		9176529
3553	IL1B	KINASE, DRUGGABLE GENOME		RESVERATROL	RESVERATROL	16389574
3553	IL1B	KINASE, DRUGGABLE GENOME		AC-201	DIACEREIN
3553	IL1B	KINASE, DRUGGABLE GENOME		XOMA 052
3553	IL1B	KINASE, DRUGGABLE GENOME		CHINESE HERBS		8871284
3553	IL1B	KINASE, DRUGGABLE GENOME		aspirin	ASPIRIN	19448967
3553	IL1B	KINASE, DRUGGABLE GENOME		ACITRETIN	ACITRETIN	1431212
3553	IL1B	KINASE, DRUGGABLE GENOME		risedronate	RISEDRONIC ACID	16257277

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