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: DIP2B

Gene summary for DIP2B

Gene summary.

Gene information	Species	Human
	Gene symbol	DIP2B
	Gene ID	57609
	Gene name	disco interacting protein 2 homolog B
	Gene Alias	DIP2B
	Cytomap	12q13.12
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	Q7Z3H2

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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
57609	DIP2B	CCI_1	Human	Cervix	CC	9.65e-16	1.76e+00	0.528
57609	DIP2B	CCI_2	Human	Cervix	CC	6.99e-17	1.54e+00	0.5249
57609	DIP2B	CCI_3	Human	Cervix	CC	2.44e-19	1.75e+00	0.516
57609	DIP2B	sample3	Human	Cervix	CC	3.24e-02	1.72e-01	0.1387
57609	DIP2B	T3	Human	Cervix	CC	9.64e-04	1.60e-01	0.1389
57609	DIP2B	HTA11_3410_2000001011	Human	Colorectum	AD	3.02e-12	-4.95e-01	0.0155
57609	DIP2B	HTA11_347_2000001011	Human	Colorectum	AD	6.93e-08	5.22e-01	-0.1954
57609	DIP2B	HTA11_866_3004761011	Human	Colorectum	AD	1.99e-07	-4.42e-01	0.096
57609	DIP2B	HTA11_99999973899_84307	Human	Colorectum	MSS	2.60e-02	-5.39e-01	0.2585
57609	DIP2B	HTA11_99999974143_84620	Human	Colorectum	MSS	1.51e-15	-5.76e-01	0.3005
57609	DIP2B	F007	Human	Colorectum	FAP	6.95e-04	-2.62e-01	0.1176
57609	DIP2B	A001-C-207	Human	Colorectum	FAP	1.09e-03	-2.35e-01	0.1278
57609	DIP2B	A015-C-203	Human	Colorectum	FAP	3.74e-42	-7.16e-01	-0.1294
57609	DIP2B	A015-C-204	Human	Colorectum	FAP	1.18e-11	-4.69e-01	-0.0228
57609	DIP2B	A014-C-040	Human	Colorectum	FAP	5.40e-09	-6.08e-01	-0.1184
57609	DIP2B	A002-C-201	Human	Colorectum	FAP	1.19e-26	-6.66e-01	0.0324
57609	DIP2B	A002-C-203	Human	Colorectum	FAP	5.96e-07	-2.82e-01	0.2786
57609	DIP2B	A001-C-119	Human	Colorectum	FAP	6.03e-08	-2.81e-01	-0.1557
57609	DIP2B	A001-C-108	Human	Colorectum	FAP	4.03e-22	-3.68e-01	-0.0272
57609	DIP2B	A002-C-205	Human	Colorectum	FAP	3.70e-34	-6.06e-01	-0.1236

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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

∗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:006056015	Oral cavity	EOLP	developmental growth involved in morphogenesis	41/2218	234/18723	6.54e-03	3.21e-02	41
GO:003030812	Oral cavity	EOLP	negative regulation of cell growth	34/2218	188/18723	7.73e-03	3.69e-02	34
GO:000740910	Oral cavity	EOLP	axonogenesis	66/2218	418/18723	8.99e-03	4.13e-02	66
GO:003134521	Oral cavity	EOLP	negative regulation of cell projection organization	33/2218	186/18723	1.14e-02	4.99e-02	33
GO:006156414	Oral cavity	EOLP	axon development	72/2218	467/18723	1.14e-02	5.00e-02	72
GO:001604931	Oral cavity	NEOLP	cell growth	90/2005	482/18723	9.23e-08	3.43e-06	90
GO:003253532	Oral cavity	NEOLP	regulation of cellular component size	73/2005	383/18723	6.70e-07	1.93e-05	73
GO:000155831	Oral cavity	NEOLP	regulation of cell growth	73/2005	414/18723	1.23e-05	2.23e-04	73
GO:001097521	Oral cavity	NEOLP	regulation of neuron projection development	77/2005	445/18723	1.44e-05	2.53e-04	77
GO:004867521	Oral cavity	NEOLP	axon extension	29/2005	120/18723	1.97e-05	3.29e-04	29
GO:006156421	Oral cavity	NEOLP	axon development	78/2005	467/18723	4.49e-05	6.26e-04	78
GO:000740914	Oral cavity	NEOLP	axonogenesis	71/2005	418/18723	5.64e-05	7.62e-04	71
GO:001820531	Oral cavity	NEOLP	peptidyl-lysine modification	64/2005	376/18723	1.21e-04	1.43e-03	64
GO:005076721	Oral cavity	NEOLP	regulation of neurogenesis	62/2005	364/18723	1.50e-04	1.71e-03	62
GO:004592621	Oral cavity	NEOLP	negative regulation of growth	46/2005	249/18723	1.58e-04	1.77e-03	46
GO:006056022	Oral cavity	NEOLP	developmental growth involved in morphogenesis	43/2005	234/18723	2.87e-04	2.86e-03	43
GO:199013822	Oral cavity	NEOLP	neuron projection extension	34/2005	172/18723	3.02e-04	2.98e-03	34
GO:003030821	Oral cavity	NEOLP	negative regulation of cell growth	36/2005	188/18723	3.88e-04	3.63e-03	36
GO:004858822	Oral cavity	NEOLP	developmental cell growth	41/2005	234/18723	1.05e-03	8.00e-03	41
GO:005196012	Oral cavity	NEOLP	regulation of nervous system development	68/2005	443/18723	1.46e-03	1.03e-02	68

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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

DIP2B

SNV

Missense_Mutation

c.3997N>A

p.Asp1333Asn

p.D1333N

Q9P265

protein_coding

deleterious(0.03)

probably_damaging(1)

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

DIP2B

SNV

Missense_Mutation

c.4606G>C

p.Val1536Leu

p.V1536L

Q9P265

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-A8-A09C-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DIP2B

SNV

Missense_Mutation

c.2437N>T

p.Asp813Tyr

p.D813Y

Q9P265

protein_coding

deleterious(0)

probably_damaging(0.988)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DIP2B

SNV

Missense_Mutation

c.4702N>C

p.Asp1568His

p.D1568H

Q9P265

protein_coding

tolerated(0.07)

probably_damaging(0.996)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DIP2B

SNV

Missense_Mutation

novel

c.3082A>G

p.Lys1028Glu

p.K1028E

Q9P265

protein_coding

deleterious(0.02)

probably_damaging(0.947)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DIP2B

SNV

Missense_Mutation

c.4214A>C

p.Tyr1405Ser

p.Y1405S

Q9P265

protein_coding

deleterious(0.01)

possibly_damaging(0.906)

TCGA-AO-A12H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

DIP2B

SNV

Missense_Mutation

novel

c.1694N>T

p.Ala565Val

p.A565V

Q9P265

protein_coding

tolerated(1)

benign(0.052)

TCGA-BH-A5IZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

DIP2B

SNV

Missense_Mutation

c.2918N>T

p.Gly973Val

p.G973V

Q9P265

protein_coding

deleterious(0)

probably_damaging(0.932)

TCGA-D8-A1XY-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

tamoxiphen

DIP2B

SNV

Missense_Mutation

c.4058A>G

p.Glu1353Gly

p.E1353G

Q9P265

protein_coding

tolerated(0.07)

probably_damaging(1)

TCGA-E2-A10A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

zoladex

DIP2B

SNV

Missense_Mutation

c.2799N>C

p.Met933Ile

p.M933I

Q9P265

protein_coding

deleterious(0.01)

benign(0.08)

TCGA-E9-A295-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

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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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