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: CIB1

Gene summary for CIB1

Gene summary.

Gene information	Species	Human
	Gene symbol	CIB1
	Gene ID	10519
	Gene name	calcium and integrin binding 1
	Gene Alias	CIB
	Cytomap	15q26.1
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q99828

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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
10519	CIB1	GSM4909282	Human	Breast	IDC	2.43e-15	4.63e-01	-0.0288
10519	CIB1	GSM4909286	Human	Breast	IDC	4.79e-06	-3.36e-01	0.1081
10519	CIB1	GSM4909290	Human	Breast	IDC	6.75e-03	3.10e-01	0.2096
10519	CIB1	GSM4909291	Human	Breast	IDC	1.51e-09	5.04e-01	0.1753
10519	CIB1	GSM4909293	Human	Breast	IDC	3.12e-03	1.72e-01	0.1581
10519	CIB1	GSM4909294	Human	Breast	IDC	3.34e-03	2.40e-01	0.2022
10519	CIB1	GSM4909296	Human	Breast	IDC	4.88e-08	2.47e-01	0.1524
10519	CIB1	GSM4909297	Human	Breast	IDC	4.39e-09	-2.56e-01	0.1517
10519	CIB1	GSM4909304	Human	Breast	IDC	5.91e-67	8.85e-01	0.1636
10519	CIB1	GSM4909306	Human	Breast	IDC	1.25e-07	3.58e-01	0.1564
10519	CIB1	GSM4909307	Human	Breast	IDC	1.96e-05	3.44e-01	0.1569
10519	CIB1	GSM4909308	Human	Breast	IDC	1.94e-11	3.65e-01	0.158
10519	CIB1	GSM4909311	Human	Breast	IDC	2.56e-24	-1.47e-01	0.1534
10519	CIB1	GSM4909312	Human	Breast	IDC	1.08e-04	1.25e-04	0.1552
10519	CIB1	GSM4909315	Human	Breast	IDC	2.32e-10	3.85e-01	0.21
10519	CIB1	GSM4909319	Human	Breast	IDC	5.11e-30	-3.06e-01	0.1563
10519	CIB1	GSM4909321	Human	Breast	IDC	2.20e-13	1.74e-01	0.1559
10519	CIB1	ctrl6	Human	Breast	Precancer	7.31e-12	6.43e-01	-0.0061
10519	CIB1	brca2	Human	Breast	Precancer	1.05e-24	5.10e-01	-0.024
10519	CIB1	brca3	Human	Breast	Precancer	4.76e-11	3.63e-01	-0.0263

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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
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:000155811	Liver	Cirrhotic	regulation of cell growth	132/4634	414/18723	5.53e-04	4.36e-03	132
GO:00713566	Liver	Cirrhotic	cellular response to tumor necrosis factor	79/4634	229/18723	5.68e-04	4.45e-03	79
GO:00107205	Liver	Cirrhotic	positive regulation of cell development	99/4634	298/18723	5.71e-04	4.46e-03	99
GO:199009011	Liver	Cirrhotic	cellular response to nerve growth factor stimulus	24/4634	53/18723	8.86e-04	6.37e-03	24
GO:199008911	Liver	Cirrhotic	response to nerve growth factor	25/4634	56/18723	9.03e-04	6.46e-03	25
GO:19030786	Liver	Cirrhotic	positive regulation of protein localization to plasma membrane	26/4634	62/18723	2.18e-03	1.34e-02	26
GO:000166712	Liver	Cirrhotic	ameboidal-type cell migration	145/4634	475/18723	2.23e-03	1.36e-02	145
GO:00106327	Liver	Cirrhotic	regulation of epithelial cell migration	93/4634	292/18723	3.46e-03	1.92e-02	93
GO:00106317	Liver	Cirrhotic	epithelial cell migration	110/4634	357/18723	5.14e-03	2.65e-02	110
GO:007190011	Liver	Cirrhotic	regulation of protein serine/threonine kinase activity	110/4634	359/18723	6.19e-03	3.08e-02	110
GO:00901327	Liver	Cirrhotic	epithelium migration	110/4634	360/18723	6.79e-03	3.35e-02	110
GO:004586011	Liver	Cirrhotic	positive regulation of protein kinase activity	117/4634	386/18723	7.07e-03	3.41e-02	117
GO:00456377	Liver	Cirrhotic	regulation of myeloid cell differentiation	68/4634	210/18723	7.40e-03	3.53e-02	68
GO:00901307	Liver	Cirrhotic	tissue migration	111/4634	365/18723	7.66e-03	3.61e-02	111
GO:0090313	Liver	Cirrhotic	regulation of protein targeting to membrane	16/4634	36/18723	7.70e-03	3.63e-02	16
GO:00705072	Liver	Cirrhotic	regulation of microtubule cytoskeleton organization	50/4634	148/18723	8.33e-03	3.87e-02	50
GO:00106346	Liver	Cirrhotic	positive regulation of epithelial cell migration	58/4634	176/18723	8.54e-03	3.96e-02	58
GO:190382922	Liver	HCC	positive regulation of cellular protein localization	199/7958	276/18723	1.15e-23	2.62e-21	199
GO:000660512	Liver	HCC	protein targeting	219/7958	314/18723	7.74e-23	1.49e-20	219
GO:003238621	Liver	HCC	regulation of intracellular transport	231/7958	337/18723	1.99e-22	3.40e-20	231

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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

CIB1

insertion

Frame_Shift_Ins

novel

c.258_259insGAGCGTGGAG

p.Ser87GlufsTer44

p.S87Efs*44

Q99828

protein_coding

TCGA-A2-A0EQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

CIB1

SNV

Missense_Mutation

c.43N>A

p.Glu15Lys

p.E15K

Q99828

protein_coding

deleterious(0.03)

possibly_damaging(0.551)

TCGA-C5-A7CK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CIB1

SNV

Missense_Mutation

rs771152399

c.686N>C

p.Ile229Thr

p.I229T

Q99828

protein_coding

deleterious(0)

probably_damaging(0.979)

TCGA-AA-3811-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

CIB1

SNV

Missense_Mutation

novel

c.665N>G

p.Asp222Gly

p.D222G

Q99828

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

CIB1

SNV

Missense_Mutation

novel

c.82N>A

p.Leu28Ile

p.L28I

Q99828

protein_coding

tolerated(0.11)

benign(0.065)

TCGA-AX-A2HD-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

CIB1

SNV

Missense_Mutation

c.581N>G

p.Asp194Gly

p.D194G

Q99828

protein_coding

tolerated(0.09)

benign(0.071)

TCGA-B5-A11G-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CIB1

SNV

Missense_Mutation

rs145803459

c.656N>A

p.Arg219His

p.R219H

Q99828

protein_coding

deleterious(0)

probably_damaging(0.961)

TCGA-BG-A220-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CIB1

SNV

Missense_Mutation

novel

c.248G>T

p.Arg83Leu

p.R83L

Q99828

protein_coding

tolerated(0.14)

benign(0.168)

TCGA-DF-A2KY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

CIB1

SNV

Missense_Mutation

c.686T>G

p.Ile229Ser

p.I229S

Q99828

protein_coding

deleterious(0)

probably_damaging(0.991)

TCGA-G3-A3CK-01

Liver

liver hepatocellular carcinoma

Male

<65

I/II

Unknown

CIB1

SNV

Missense_Mutation

rs765061684

c.538N>A

p.Glu180Lys

p.E180K

Q99828

protein_coding

tolerated(0.1)

benign(0.216)

TCGA-39-5031-01

Lung

lung squamous cell 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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