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: CIR1

Gene summary for CIR1

Gene summary.

Gene information	Species	Human
	Gene symbol	CIR1
	Gene ID	9541
	Gene name	corepressor interacting with RBPJ, CIR1
	Gene Alias	CIR
	Cytomap	2q31.1
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	Q86X95

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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
9541	CIR1	LZE4T	Human	Esophagus	ESCC	9.81e-12	4.41e-01	0.0811
9541	CIR1	LZE5T	Human	Esophagus	ESCC	2.32e-04	4.55e-01	0.0514
9541	CIR1	LZE7T	Human	Esophagus	ESCC	3.67e-05	3.93e-01	0.0667
9541	CIR1	LZE8T	Human	Esophagus	ESCC	1.34e-03	9.69e-02	0.067
9541	CIR1	LZE20T	Human	Esophagus	ESCC	6.17e-16	2.77e-01	0.0662
9541	CIR1	LZE22D1	Human	Esophagus	HGIN	4.45e-07	1.53e-01	0.0595
9541	CIR1	LZE22T	Human	Esophagus	ESCC	3.94e-03	4.97e-01	0.068
9541	CIR1	LZE24T	Human	Esophagus	ESCC	3.55e-12	5.16e-01	0.0596
9541	CIR1	LZE21T	Human	Esophagus	ESCC	9.87e-05	2.09e-01	0.0655
9541	CIR1	LZE6T	Human	Esophagus	ESCC	6.04e-09	1.14e-01	0.0845
9541	CIR1	P1T-E	Human	Esophagus	ESCC	1.89e-04	4.70e-01	0.0875
9541	CIR1	P2T-E	Human	Esophagus	ESCC	7.56e-27	3.58e-01	0.1177
9541	CIR1	P4T-E	Human	Esophagus	ESCC	3.67e-27	6.59e-01	0.1323
9541	CIR1	P5T-E	Human	Esophagus	ESCC	2.37e-20	2.58e-01	0.1327
9541	CIR1	P8T-E	Human	Esophagus	ESCC	3.21e-34	7.70e-01	0.0889
9541	CIR1	P9T-E	Human	Esophagus	ESCC	8.25e-43	1.12e+00	0.1131
9541	CIR1	P10T-E	Human	Esophagus	ESCC	1.28e-27	6.13e-01	0.116
9541	CIR1	P11T-E	Human	Esophagus	ESCC	1.58e-20	7.43e-01	0.1426
9541	CIR1	P12T-E	Human	Esophagus	ESCC	1.99e-30	7.76e-01	0.1122
9541	CIR1	P15T-E	Human	Esophagus	ESCC	3.41e-28	6.84e-01	0.1149

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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
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:000838026	Esophagus	HGIN	RNA splicing	160/2587	434/18723	3.74e-34	1.12e-30	160
GO:000170118	Esophagus	HGIN	in utero embryonic development	77/2587	367/18723	9.56e-05	2.05e-03	77
GO:0008380111	Esophagus	ESCC	RNA splicing	336/8552	434/18723	1.74e-42	3.67e-39	336
GO:000170119	Esophagus	ESCC	in utero embryonic development	243/8552	367/18723	1.00e-15	6.86e-14	243
GO:000838012	Liver	Cirrhotic	RNA splicing	229/4634	434/18723	9.13e-37	2.86e-33	229
GO:00017015	Liver	Cirrhotic	in utero embryonic development	134/4634	367/18723	2.78e-07	6.86e-06	134
GO:000838022	Liver	HCC	RNA splicing	313/7958	434/18723	1.36e-36	1.73e-33	313
GO:000170111	Liver	HCC	in utero embryonic development	204/7958	367/18723	2.44e-07	4.30e-06	204
GO:000838020	Oral cavity	OSCC	RNA splicing	308/7305	434/18723	2.43e-42	7.70e-39	308
GO:000170116	Oral cavity	OSCC	in utero embryonic development	207/7305	367/18723	7.92e-12	2.95e-10	207
GO:0008380110	Oral cavity	LP	RNA splicing	237/4623	434/18723	1.82e-41	3.79e-38	237
GO:000170117	Oral cavity	LP	in utero embryonic development	142/4623	367/18723	1.48e-09	6.75e-08	142
GO:000838018	Prostate	BPH	RNA splicing	147/3107	434/18723	5.17e-19	2.29e-16	147
GO:000170110	Prostate	BPH	in utero embryonic development	104/3107	367/18723	9.17e-09	3.10e-07	104
GO:000838019	Prostate	Tumor	RNA splicing	153/3246	434/18723	9.15e-20	5.79e-17	153
GO:000170115	Prostate	Tumor	in utero embryonic development	106/3246	367/18723	2.37e-08	8.09e-07	106
GO:0008380112	Skin	cSCC	RNA splicing	263/4864	434/18723	2.45e-53	5.13e-50	263
GO:000170124	Skin	cSCC	in utero embryonic development	150/4864	367/18723	2.47e-10	1.04e-08	150
GO:0008380113	Thyroid	PTC	RNA splicing	273/5968	434/18723	4.44e-41	1.40e-37	273
GO:0001701111	Thyroid	PTC	in utero embryonic development	175/5968	367/18723	1.40e-10	4.73e-09	175

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0516930	Esophagus	HGIN	Epstein-Barr virus infection	55/1383	202/8465	5.13e-05	6.19e-04	4.92e-04	55
hsa05169114	Esophagus	HGIN	Epstein-Barr virus infection	55/1383	202/8465	5.13e-05	6.19e-04	4.92e-04	55
hsa05169210	Esophagus	ESCC	Epstein-Barr virus infection	151/4205	202/8465	1.55e-13	3.45e-12	1.77e-12	151
hsa043306	Esophagus	ESCC	Notch signaling pathway	42/4205	62/8465	2.97e-03	7.97e-03	4.08e-03	42
hsa0516937	Esophagus	ESCC	Epstein-Barr virus infection	151/4205	202/8465	1.55e-13	3.45e-12	1.77e-12	151
hsa0433013	Esophagus	ESCC	Notch signaling pathway	42/4205	62/8465	2.97e-03	7.97e-03	4.08e-03	42
hsa0516914	Liver	Cirrhotic	Epstein-Barr virus infection	80/2530	202/8465	1.80e-03	8.33e-03	5.13e-03	80
hsa0516915	Liver	Cirrhotic	Epstein-Barr virus infection	80/2530	202/8465	1.80e-03	8.33e-03	5.13e-03	80
hsa0516921	Liver	HCC	Epstein-Barr virus infection	128/4020	202/8465	3.17e-06	2.79e-05	1.55e-05	128
hsa0516931	Liver	HCC	Epstein-Barr virus infection	128/4020	202/8465	3.17e-06	2.79e-05	1.55e-05	128
hsa0516928	Oral cavity	OSCC	Epstein-Barr virus infection	144/3704	202/8465	1.08e-15	3.60e-14	1.83e-14	144
hsa043305	Oral cavity	OSCC	Notch signaling pathway	44/3704	62/8465	1.26e-05	5.55e-05	2.83e-05	44
hsa05169113	Oral cavity	OSCC	Epstein-Barr virus infection	144/3704	202/8465	1.08e-15	3.60e-14	1.83e-14	144
hsa0433012	Oral cavity	OSCC	Notch signaling pathway	44/3704	62/8465	1.26e-05	5.55e-05	2.83e-05	44
hsa0516929	Oral cavity	LP	Epstein-Barr virus infection	106/2418	202/8465	4.30e-13	9.54e-12	6.15e-12	106
hsa0516936	Oral cavity	LP	Epstein-Barr virus infection	106/2418	202/8465	4.30e-13	9.54e-12	6.15e-12	106
hsa0516926	Prostate	BPH	Epstein-Barr virus infection	70/1718	202/8465	1.06e-06	9.74e-06	6.03e-06	70
hsa043304	Prostate	BPH	Notch signaling pathway	21/1718	62/8465	8.53e-03	2.68e-02	1.66e-02	21
hsa05169112	Prostate	BPH	Epstein-Barr virus infection	70/1718	202/8465	1.06e-06	9.74e-06	6.03e-06	70
hsa0433011	Prostate	BPH	Notch signaling pathway	21/1718	62/8465	8.53e-03	2.68e-02	1.66e-02	21

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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

CIR1

SNV

Missense_Mutation

c.698N>G

p.Lys233Arg

p.K233R

Q86X95

protein_coding

tolerated(0.1)

possibly_damaging(0.763)

TCGA-A8-A08Z-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

CIR1

SNV

Missense_Mutation

novel

c.1114N>A

p.Glu372Lys

p.E372K

Q86X95

protein_coding

deleterious_low_confidence(0.02)

benign(0.081)

TCGA-A8-A0A7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CIR1

SNV

Missense_Mutation

novel

c.1237G>A

p.Glu413Lys

p.E413K

Q86X95

protein_coding

tolerated_low_confidence(0.09)

benign(0.006)

TCGA-BH-A42V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CIR1

SNV

Missense_Mutation

rs200291230

c.631N>A

p.Glu211Lys

p.E211K

Q86X95

protein_coding

tolerated(0.09)

probably_damaging(0.994)

TCGA-D8-A27L-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin+cuclophosphamide

CIR1

SNV

Missense_Mutation

rs531011902

c.1162C>T

p.Arg388Trp

p.R388W

Q86X95

protein_coding

deleterious_low_confidence(0.03)

possibly_damaging(0.734)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CIR1

SNV

Missense_Mutation

novel

c.925N>A

p.Glu309Lys

p.E309K

Q86X95

protein_coding

tolerated_low_confidence(0.06)

benign(0.154)

TCGA-EA-A3Y4-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

CIR1

SNV

Missense_Mutation

novel

c.831T>A

p.Ser277Arg

p.S277R

Q86X95

protein_coding

deleterious_low_confidence(0.03)

probably_damaging(0.996)

TCGA-VS-A9UC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CIR1

SNV

Missense_Mutation

rs762930010

c.1216N>T

p.Arg406Trp

p.R406W

Q86X95

protein_coding

tolerated_low_confidence(0.25)

benign(0)

TCGA-AA-3870-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Chemotherapy

folinic

CIR1

SNV

Missense_Mutation

rs768225837

c.464C>T

p.Ser155Leu

p.S155L

Q86X95

protein_coding

deleterious(0)

possibly_damaging(0.9)

TCGA-AA-3984-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

CIR1

SNV

Missense_Mutation

novel

c.1280N>C

p.Asp427Ala

p.D427A

Q86X95

protein_coding

deleterious_low_confidence(0.01)

benign(0.039)

TCGA-AZ-4315-01

Colorectum

colon adenocarcinoma

Male

<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

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