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: ITPR1

Gene summary for ITPR1

Gene summary.

Gene information	Species	Human
	Gene symbol	ITPR1
	Gene ID	3708
	Gene name	inositol 1,4,5-trisphosphate receptor type 1
	Gene Alias	ACV
	Cytomap	3p26.1
	Gene Type	protein-coding
	GO ID	GO:0001666
	UniProtAcc	B4DER3

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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
3708	ITPR1	LZE4T	Human	Esophagus	ESCC	7.61e-05	1.40e-01	0.0811
3708	ITPR1	P2T-E	Human	Esophagus	ESCC	7.13e-05	1.98e-02	0.1177
3708	ITPR1	P4T-E	Human	Esophagus	ESCC	4.51e-12	1.66e-01	0.1323
3708	ITPR1	P5T-E	Human	Esophagus	ESCC	1.02e-07	8.34e-02	0.1327
3708	ITPR1	P9T-E	Human	Esophagus	ESCC	9.55e-05	1.78e-01	0.1131
3708	ITPR1	P11T-E	Human	Esophagus	ESCC	1.03e-04	5.89e-01	0.1426
3708	ITPR1	P15T-E	Human	Esophagus	ESCC	3.90e-02	1.23e-01	0.1149
3708	ITPR1	P16T-E	Human	Esophagus	ESCC	2.37e-04	-3.56e-03	0.1153
3708	ITPR1	P21T-E	Human	Esophagus	ESCC	1.86e-03	-3.66e-03	0.1617
3708	ITPR1	P23T-E	Human	Esophagus	ESCC	7.28e-10	1.37e-01	0.108
3708	ITPR1	P24T-E	Human	Esophagus	ESCC	8.40e-03	2.93e-02	0.1287
3708	ITPR1	P26T-E	Human	Esophagus	ESCC	4.01e-08	6.80e-02	0.1276
3708	ITPR1	P27T-E	Human	Esophagus	ESCC	6.35e-08	1.57e-01	0.1055
3708	ITPR1	P28T-E	Human	Esophagus	ESCC	2.68e-08	8.87e-02	0.1149
3708	ITPR1	P32T-E	Human	Esophagus	ESCC	1.96e-19	5.74e-01	0.1666
3708	ITPR1	P37T-E	Human	Esophagus	ESCC	1.29e-11	2.22e-01	0.1371
3708	ITPR1	P40T-E	Human	Esophagus	ESCC	5.89e-03	8.91e-02	0.109
3708	ITPR1	P42T-E	Human	Esophagus	ESCC	1.68e-02	8.06e-02	0.1175
3708	ITPR1	P49T-E	Human	Esophagus	ESCC	2.45e-02	3.42e-01	0.1768
3708	ITPR1	P52T-E	Human	Esophagus	ESCC	2.71e-04	4.86e-03	0.1555

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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
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:0097193111	Esophagus	ESCC	intrinsic apoptotic signaling pathway	222/8552	288/18723	5.87e-28	2.02e-25	222
GO:0034976111	Esophagus	ESCC	response to endoplasmic reticulum stress	192/8552	256/18723	7.15e-22	1.30e-19	192
GO:001050617	Esophagus	ESCC	regulation of autophagy	220/8552	317/18723	6.72e-18	6.36e-16	220
GO:0070482111	Esophagus	ESCC	response to oxygen levels	218/8552	347/18723	6.91e-11	2.17e-09	218
GO:0036293111	Esophagus	ESCC	response to decreased oxygen levels	201/8552	322/18723	8.37e-10	2.04e-08	201
GO:0001666111	Esophagus	ESCC	response to hypoxia	192/8552	307/18723	1.59e-09	3.69e-08	192
GO:0051235110	Esophagus	ESCC	maintenance of location	200/8552	327/18723	1.01e-08	2.02e-07	200
GO:0070059111	Esophagus	ESCC	intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	50/8552	63/18723	4.37e-08	7.96e-07	50
GO:00097919	Esophagus	ESCC	post-embryonic development	56/8552	80/18723	9.08e-06	8.71e-05	56
GO:0051651111	Esophagus	ESCC	maintenance of location in cell	126/8552	214/18723	6.57e-05	5.00e-04	126
GO:0032469110	Esophagus	ESCC	endoplasmic reticulum calcium ion homeostasis	21/8552	25/18723	9.12e-05	6.54e-04	21
GO:009719330	Thyroid	HT	intrinsic apoptotic signaling pathway	52/1272	288/18723	7.65e-11	1.06e-08	52
GO:003497627	Thyroid	HT	response to endoplasmic reticulum stress	41/1272	256/18723	2.43e-07	1.20e-05	41
GO:007048227	Thyroid	HT	response to oxygen levels	50/1272	347/18723	3.61e-07	1.65e-05	50
GO:003629327	Thyroid	HT	response to decreased oxygen levels	46/1272	322/18723	1.34e-06	5.14e-05	46
GO:000166627	Thyroid	HT	response to hypoxia	44/1272	307/18723	2.07e-06	7.53e-05	44
GO:003246924	Thyroid	HT	endoplasmic reticulum calcium ion homeostasis	7/1272	25/18723	1.07e-03	1.07e-02	7
GO:005165129	Thyroid	HT	maintenance of location in cell	27/1272	214/18723	1.39e-03	1.32e-02	27
GO:001050620	Thyroid	HT	regulation of autophagy	35/1272	317/18723	3.15e-03	2.52e-02	35
GO:005123528	Thyroid	HT	maintenance of location	35/1272	327/18723	5.16e-03	3.47e-02	35

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05016210	Esophagus	ESCC	Huntington disease	226/4205	306/8465	1.38e-18	8.72e-17	4.46e-17	226
hsa05012211	Esophagus	ESCC	Parkinson disease	201/4205	266/8465	1.56e-18	8.72e-17	4.46e-17	201
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
hsa05020210	Esophagus	ESCC	Prion disease	193/4205	273/8465	6.42e-13	1.34e-11	6.89e-12	193
hsa05131211	Esophagus	ESCC	Shigellosis	176/4205	247/8465	2.27e-12	4.01e-11	2.05e-11	176
hsa0421829	Esophagus	ESCC	Cellular senescence	119/4205	156/8465	5.89e-12	9.40e-11	4.81e-11	119
hsa0421027	Esophagus	ESCC	Apoptosis	102/4205	136/8465	1.05e-09	1.21e-08	6.21e-09	102
hsa05170210	Esophagus	ESCC	Human immunodeficiency virus 1 infection	147/4205	212/8465	3.37e-09	3.53e-08	1.81e-08	147
hsa05167211	Esophagus	ESCC	Kaposi sarcoma-associated herpesvirus infection	136/4205	194/8465	4.28e-09	4.22e-08	2.16e-08	136
hsa0414010	Esophagus	ESCC	Autophagy - animal	101/4205	141/8465	7.60e-08	6.21e-07	3.18e-07	101
hsa0520529	Esophagus	ESCC	Proteoglycans in cancer	138/4205	205/8465	1.79e-07	1.40e-06	7.15e-07	138
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
hsa046259	Esophagus	ESCC	C-type lectin receptor signaling pathway	73/4205	104/8465	1.57e-05	7.98e-05	4.09e-05	73
hsa0501728	Esophagus	ESCC	Spinocerebellar ataxia	94/4205	143/8465	6.77e-05	2.90e-04	1.48e-04	94
hsa0462122	Esophagus	ESCC	NOD-like receptor signaling pathway	116/4205	186/8465	2.90e-04	1.03e-03	5.30e-04	116
hsa0492816	Esophagus	ESCC	Parathyroid hormone synthesis, secretion and action	66/4205	106/8465	5.86e-03	1.47e-02	7.51e-03	66
hsa0492214	Esophagus	ESCC	Glucagon signaling pathway	64/4205	107/8465	2.18e-02	4.80e-02	2.46e-02	64
hsa041146	Esophagus	ESCC	Oocyte meiosis	77/4205	131/8465	2.19e-02	4.80e-02	2.46e-02	77

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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

ITPR1

SNV

Missense_Mutation

c.5130N>T

p.Glu1710Asp

p.E1710D

Q14643

protein_coding

tolerated(0.2)

benign(0)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

ITPR1

SNV

Missense_Mutation

rs779313917

c.6832N>A

p.Val2278Ile

p.V2278I

Q14643

protein_coding

tolerated(0.13)

benign(0.036)

TCGA-A2-A4S3-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ITPR1

SNV

Missense_Mutation

c.7417G>A

p.Val2473Ile

p.V2473I

Q14643

protein_coding

tolerated(0.47)

benign(0.009)

TCGA-A8-A09B-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

5-fluorouracil

ITPR1

SNV

Missense_Mutation

rs768179678

c.3721G>A

p.Ala1241Thr

p.A1241T

Q14643

protein_coding

tolerated(0.43)

benign(0.103)

TCGA-A8-A09W-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

ITPR1

SNV

Missense_Mutation

novel

c.3631N>A

p.Glu1211Lys

p.E1211K

Q14643

protein_coding

deleterious(0.02)

possibly_damaging(0.808)

TCGA-A8-A0A7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ITPR1

SNV

Missense_Mutation

rs373174492

c.977N>A

p.Arg326Gln

p.R326Q

Q14643

protein_coding

deleterious(0.01)

possibly_damaging(0.595)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ITPR1

SNV

Missense_Mutation

c.5547N>A

p.Phe1849Leu

p.F1849L

Q14643

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ITPR1

SNV

Missense_Mutation

c.6103N>A

p.Glu2035Lys

p.E2035K

Q14643

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ITPR1

SNV

Missense_Mutation

c.2677N>G

p.Ser893Gly

p.S893G

Q14643

protein_coding

tolerated(0.47)

benign(0)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ITPR1

SNV

Missense_Mutation

novel

c.3487A>C

p.Thr1163Pro

p.T1163P

Q14643

protein_coding

tolerated(0.19)

benign(0.162)

TCGA-B6-A1KN-01

Breast

breast invasive carcinoma

Female

<65

III/IV

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
3708	ITPR1	ION CHANNEL, KINASE, DRUGGABLE GENOME, TRANSPORTER	antagonist	135651544
3708	ITPR1	ION CHANNEL, KINASE, DRUGGABLE GENOME, TRANSPORTER	activator	178101039
3708	ITPR1	ION CHANNEL, KINASE, DRUGGABLE GENOME, TRANSPORTER	activator	135652731
3708	ITPR1	ION CHANNEL, KINASE, DRUGGABLE GENOME, TRANSPORTER	antagonist	135652750
3708	ITPR1	ION CHANNEL, KINASE, DRUGGABLE GENOME, TRANSPORTER	activator	178100946
3708	ITPR1	ION CHANNEL, KINASE, DRUGGABLE GENOME, TRANSPORTER	antagonist	178101161
3708	ITPR1	ION CHANNEL, KINASE, DRUGGABLE GENOME, TRANSPORTER	activator	178101040
3708	ITPR1	ION CHANNEL, KINASE, DRUGGABLE GENOME, TRANSPORTER	antagonist	135652675	CAFFEINE
3708	ITPR1	ION CHANNEL, KINASE, DRUGGABLE GENOME, TRANSPORTER	activator	135651446	ADENOSINE TRIPHOSPHATE
3708	ITPR1	ION CHANNEL, KINASE, DRUGGABLE GENOME, TRANSPORTER		Nitroprusside	NITROPRUSSIDE

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