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: CLIC1

Gene summary for CLIC1

Gene summary.

Gene information	Species	Human
	Gene symbol	CLIC1
	Gene ID	1192
	Gene name	chloride intracellular channel 1
	Gene Alias	CL1C1
	Cytomap	6p21.33
	Gene Type	protein-coding
	GO ID	GO:0001503
	UniProtAcc	O00299

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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
1192	CLIC1	GSM4909286	Human	Breast	IDC	3.13e-29	-5.38e-01	0.1081
1192	CLIC1	GSM4909287	Human	Breast	IDC	1.01e-09	-4.96e-01	0.2057
1192	CLIC1	GSM4909288	Human	Breast	IDC	2.69e-02	-4.16e-01	0.0988
1192	CLIC1	GSM4909293	Human	Breast	IDC	2.40e-18	-3.16e-01	0.1581
1192	CLIC1	GSM4909294	Human	Breast	IDC	2.74e-10	-4.59e-01	0.2022
1192	CLIC1	GSM4909296	Human	Breast	IDC	4.02e-10	-2.30e-01	0.1524
1192	CLIC1	GSM4909297	Human	Breast	IDC	1.02e-20	-3.05e-01	0.1517
1192	CLIC1	GSM4909298	Human	Breast	IDC	1.21e-15	-3.36e-01	0.1551
1192	CLIC1	GSM4909299	Human	Breast	IDC	4.41e-07	-3.20e-01	0.035
1192	CLIC1	GSM4909301	Human	Breast	IDC	6.64e-14	-4.78e-01	0.1577
1192	CLIC1	GSM4909302	Human	Breast	IDC	8.74e-06	-4.18e-01	0.1545
1192	CLIC1	GSM4909303	Human	Breast	IDC	3.36e-02	-4.72e-01	0.0438
1192	CLIC1	GSM4909304	Human	Breast	IDC	1.31e-14	-4.10e-01	0.1636
1192	CLIC1	GSM4909306	Human	Breast	IDC	1.49e-02	-1.91e-01	0.1564
1192	CLIC1	GSM4909311	Human	Breast	IDC	1.54e-46	-6.27e-01	0.1534
1192	CLIC1	GSM4909312	Human	Breast	IDC	6.08e-07	-6.56e-02	0.1552
1192	CLIC1	GSM4909317	Human	Breast	IDC	1.42e-05	-3.22e-01	0.1355
1192	CLIC1	GSM4909319	Human	Breast	IDC	4.43e-62	-5.83e-01	0.1563
1192	CLIC1	GSM4909320	Human	Breast	IDC	2.29e-06	-3.81e-01	0.1575
1192	CLIC1	GSM4909321	Human	Breast	IDC	1.18e-12	-2.80e-01	0.1559

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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:00518816	Breast	Precancer	regulation of mitochondrial membrane potential	18/1080	74/18723	1.45e-07	7.82e-06	18
GO:00341099	Breast	Precancer	homotypic cell-cell adhesion	18/1080	90/18723	3.15e-06	1.03e-04	18
GO:00420609	Breast	Precancer	wound healing	48/1080	422/18723	5.48e-06	1.63e-04	48
GO:00508789	Breast	Precancer	regulation of body fluid levels	40/1080	379/18723	1.68e-04	2.77e-03	40
GO:00016496	Breast	Precancer	osteoblast differentiation	27/1080	229/18723	3.35e-04	4.73e-03	27
GO:00705278	Breast	Precancer	platelet aggregation	12/1080	67/18723	4.02e-04	5.43e-03	12
GO:00075995	Breast	Precancer	hemostasis	24/1080	222/18723	2.31e-03	2.15e-02	24
GO:00075965	Breast	Precancer	blood coagulation	23/1080	217/18723	3.61e-03	2.98e-02	23
GO:00508175	Breast	Precancer	coagulation	23/1080	222/18723	4.78e-03	3.64e-02	23
GO:0030168	Breast	Precancer	platelet activation	15/1080	123/18723	4.80e-03	3.64e-02	15
GO:00015036	Breast	Precancer	ossification	36/1080	408/18723	7.53e-03	4.98e-02	36
GO:005188113	Breast	IDC	regulation of mitochondrial membrane potential	19/1434	74/18723	2.04e-06	8.27e-05	19
GO:003410913	Breast	IDC	homotypic cell-cell adhesion	20/1434	90/18723	1.20e-05	3.17e-04	20
GO:000164912	Breast	IDC	osteoblast differentiation	35/1434	229/18723	6.64e-05	1.35e-03	35
GO:004206014	Breast	IDC	wound healing	55/1434	422/18723	7.27e-05	1.45e-03	55
GO:005087813	Breast	IDC	regulation of body fluid levels	50/1434	379/18723	1.12e-04	2.10e-03	50
GO:000150311	Breast	IDC	ossification	50/1434	408/18723	6.51e-04	8.04e-03	50
GO:00423912	Breast	IDC	regulation of membrane potential	49/1434	434/18723	4.04e-03	3.25e-02	49
GO:007052713	Breast	IDC	platelet aggregation	12/1434	67/18723	4.53e-03	3.49e-02	12
GO:005188122	Breast	DCIS	regulation of mitochondrial membrane potential	19/1390	74/18723	1.28e-06	4.99e-05	19

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

CLIC1

SNV

Missense_Mutation

c.123N>A

p.Phe41Leu

p.F41L

O00299

protein_coding

deleterious(0.02)

probably_damaging(0.996)

TCGA-A8-A09G-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

CLIC1

SNV

Missense_Mutation

novel

c.484G>A

p.Val162Ile

p.V162I

O00299

protein_coding

tolerated(0.49)

benign(0)

TCGA-E2-A150-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

CLIC1

SNV

Missense_Mutation

c.667T>C

p.Cys223Arg

p.C223R

O00299

protein_coding

deleterious(0)

possibly_damaging(0.624)

TCGA-CM-6674-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

CLIC1

SNV

Missense_Mutation

novel

c.39N>T

p.Lys13Asn

p.K13N

O00299

protein_coding

deleterious(0)

possibly_damaging(0.55)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

CLIC1

SNV

Missense_Mutation

c.226G>A

p.Asp76Asn

p.D76N

O00299

protein_coding

deleterious(0.01)

probably_damaging(0.998)

TCGA-AP-A054-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

CLIC1

SNV

Missense_Mutation

rs570496971

c.100C>A

p.Leu34Met

p.L34M

O00299

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CLIC1

SNV

Missense_Mutation

novel

c.623G>A

p.Arg208Gln

p.R208Q

O00299

protein_coding

tolerated(0.06)

benign(0.015)

TCGA-AP-A1DR-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

CLIC1

SNV

Missense_Mutation

novel

c.619N>T

p.His207Tyr

p.H207Y

O00299

protein_coding

tolerated(0.11)

benign(0.075)

TCGA-AX-A1CE-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

CLIC1

SNV

Missense_Mutation

novel

c.583N>T

p.Arg195Trp

p.R195W

O00299

protein_coding

deleterious(0.04)

benign(0.009)

TCGA-AX-A2HD-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

CLIC1

SNV

Missense_Mutation

novel

c.475N>A

p.Asp159Asn

p.D159N

O00299

protein_coding

tolerated(0.25)

benign(0.028)

TCGA-B5-A3FC-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

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