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:00435427	Cervix	CC	endothelial cell migration	60/2311	279/18723	1.05e-05	2.33e-04	60
GO:004232610	Cervix	CC	negative regulation of phosphorylation	77/2311	385/18723	1.09e-05	2.38e-04	77
GO:00160498	Cervix	CC	cell growth	92/2311	482/18723	1.16e-05	2.49e-04	92
GO:00105944	Cervix	CC	regulation of endothelial cell migration	52/2311	232/18723	1.20e-05	2.54e-04	52
GO:004563710	Cervix	CC	regulation of myeloid cell differentiation	48/2311	210/18723	1.49e-05	2.93e-04	48
GO:00346129	Cervix	CC	response to tumor necrosis factor	55/2311	253/18723	1.75e-05	3.32e-04	55
GO:00713569	Cervix	CC	cellular response to tumor necrosis factor	51/2311	229/18723	1.75e-05	3.32e-04	51
GO:00719025	Cervix	CC	positive regulation of protein serine/threonine kinase activity	46/2311	200/18723	1.87e-05	3.47e-04	46
GO:19054778	Cervix	CC	positive regulation of protein localization to membrane	29/2311	106/18723	2.29e-05	4.01e-04	29
GO:000193310	Cervix	CC	negative regulation of protein phosphorylation	69/2311	342/18723	2.29e-05	4.01e-04	69
GO:19029048	Cervix	CC	negative regulation of supramolecular fiber organization	40/2311	167/18723	2.39e-05	4.17e-04	40
GO:00323889	Cervix	CC	positive regulation of intracellular transport	46/2311	202/18723	2.45e-05	4.24e-04	46
GO:00434104	Cervix	CC	positive regulation of MAPK cascade	90/2311	480/18723	2.92e-05	4.83e-04	90
GO:00107708	Cervix	CC	positive regulation of cell morphogenesis involved in differentiation	23/2311	79/18723	5.44e-05	8.04e-04	23
GO:002241110	Cervix	CC	cellular component disassembly	83/2311	443/18723	6.04e-05	8.68e-04	83
GO:19000269	Cervix	CC	positive regulation of substrate adhesion-dependent cell spreading	15/2311	41/18723	6.11e-05	8.76e-04	15
GO:00106399	Cervix	CC	negative regulation of organelle organization	68/2311	348/18723	7.40e-05	1.03e-03	68
GO:00901509	Cervix	CC	establishment of protein localization to membrane	54/2311	260/18723	7.67e-05	1.05e-03	54
GO:19030768	Cervix	CC	regulation of protein localization to plasma membrane	27/2311	104/18723	1.15e-04	1.44e-03	27
GO:00459277	Cervix	CC	positive regulation of growth	53/2311	259/18723	1.33e-04	1.64e-03	53

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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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