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: SDCBP

Gene summary for SDCBP

Gene summary.

Gene information	Species	Human
	Gene symbol	SDCBP
	Gene ID	6386
	Gene name	syndecan binding protein
	Gene Alias	MDA-9
	Cytomap	8q12.1
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	A0A024R7Z5

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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
6386	SDCBP	GSM4909285	Human	Breast	IDC	3.32e-05	-2.56e-01	0.21
6386	SDCBP	GSM4909286	Human	Breast	IDC	2.74e-11	-4.68e-01	0.1081
6386	SDCBP	GSM4909290	Human	Breast	IDC	8.18e-18	-6.68e-01	0.2096
6386	SDCBP	GSM4909293	Human	Breast	IDC	4.15e-12	-3.04e-01	0.1581
6386	SDCBP	GSM4909294	Human	Breast	IDC	9.47e-04	-3.55e-01	0.2022
6386	SDCBP	GSM4909296	Human	Breast	IDC	8.42e-29	-6.60e-01	0.1524
6386	SDCBP	GSM4909297	Human	Breast	IDC	4.15e-18	-4.88e-01	0.1517
6386	SDCBP	GSM4909298	Human	Breast	IDC	1.53e-29	-6.69e-01	0.1551
6386	SDCBP	GSM4909301	Human	Breast	IDC	1.82e-10	-4.70e-01	0.1577
6386	SDCBP	GSM4909302	Human	Breast	IDC	3.32e-07	-4.60e-01	0.1545
6386	SDCBP	GSM4909307	Human	Breast	IDC	6.93e-21	-6.26e-01	0.1569
6386	SDCBP	GSM4909308	Human	Breast	IDC	4.81e-09	-4.96e-01	0.158
6386	SDCBP	GSM4909309	Human	Breast	IDC	5.83e-11	-5.30e-01	0.0483
6386	SDCBP	GSM4909311	Human	Breast	IDC	2.14e-40	-6.79e-01	0.1534
6386	SDCBP	GSM4909312	Human	Breast	IDC	4.83e-06	-2.38e-01	0.1552
6386	SDCBP	GSM4909313	Human	Breast	IDC	7.88e-04	-3.82e-01	0.0391
6386	SDCBP	GSM4909317	Human	Breast	IDC	8.49e-05	-4.06e-01	0.1355
6386	SDCBP	GSM4909319	Human	Breast	IDC	6.98e-38	-5.15e-01	0.1563
6386	SDCBP	GSM4909320	Human	Breast	IDC	1.18e-12	-7.27e-01	0.1575
6386	SDCBP	GSM4909321	Human	Breast	IDC	4.38e-22	-5.15e-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:00458619	Breast	Precancer	negative regulation of proteolysis	50/1080	351/18723	2.99e-09	2.39e-07	50
GO:00104989	Breast	Precancer	proteasomal protein catabolic process	58/1080	490/18723	1.54e-07	8.05e-06	58
GO:19033629	Breast	Precancer	regulation of cellular protein catabolic process	36/1080	255/18723	6.03e-07	2.55e-05	36
GO:00421769	Breast	Precancer	regulation of protein catabolic process	47/1080	391/18723	1.50e-06	5.58e-05	47
GO:19030509	Breast	Precancer	regulation of proteolysis involved in cellular protein catabolic process	31/1080	221/18723	4.10e-06	1.27e-04	31
GO:00313309	Breast	Precancer	negative regulation of cellular catabolic process	34/1080	262/18723	8.16e-06	2.20e-04	34
GO:19033638	Breast	Precancer	negative regulation of cellular protein catabolic process	14/1080	75/18723	8.54e-05	1.63e-03	14
GO:00098959	Breast	Precancer	negative regulation of catabolic process	36/1080	320/18723	9.92e-05	1.83e-03	36
GO:00611369	Breast	Precancer	regulation of proteasomal protein catabolic process	24/1080	187/18723	1.99e-04	3.14e-03	24
GO:00431619	Breast	Precancer	proteasome-mediated ubiquitin-dependent protein catabolic process	42/1080	412/18723	2.49e-04	3.72e-03	42
GO:19030518	Breast	Precancer	negative regulation of proteolysis involved in cellular protein catabolic process	12/1080	64/18723	2.58e-04	3.83e-03	12
GO:20000599	Breast	Precancer	negative regulation of ubiquitin-dependent protein catabolic process	10/1080	48/18723	3.43e-04	4.81e-03	10
GO:20000589	Breast	Precancer	regulation of ubiquitin-dependent protein catabolic process	21/1080	164/18723	5.00e-04	6.53e-03	21
GO:00160497	Breast	Precancer	cell growth	46/1080	482/18723	5.63e-04	7.16e-03	46
GO:00421779	Breast	Precancer	negative regulation of protein catabolic process	17/1080	121/18723	5.76e-04	7.28e-03	17
GO:00066059	Breast	Precancer	protein targeting	33/1080	314/18723	6.50e-04	7.99e-03	33
GO:00068986	Breast	Precancer	receptor-mediated endocytosis	27/1080	244/18723	9.01e-04	1.03e-02	27
GO:19035434	Breast	Precancer	positive regulation of exosomal secretion	5/1080	15/18723	1.17e-03	1.26e-02	5
GO:00018373	Breast	Precancer	epithelial to mesenchymal transition	19/1080	157/18723	1.78e-03	1.75e-02	19
GO:00015587	Breast	Precancer	regulation of cell growth	39/1080	414/18723	1.81e-03	1.78e-02	39

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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

SDCBP

SNV

Missense_Mutation

c.263N>T

p.Arg88Leu

p.R88L

protein_coding

tolerated(0.11)

benign(0.246)

TCGA-GM-A2DD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

SDCBP

SNV

Missense_Mutation

c.574N>C

p.Asp192His

p.D192H

protein_coding

deleterious(0.03)

possibly_damaging(0.845)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

SDCBP

SNV

Missense_Mutation

rs769061064

c.893N>C

p.Ile298Thr

p.I298T

protein_coding

deleterious(0)

benign(0.197)

TCGA-DS-A0VN-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SDCBP

SNV

Missense_Mutation

c.274N>T

p.Ala92Ser

p.A92S

protein_coding

tolerated(0.54)

benign(0.042)

TCGA-JW-A69B-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SDCBP

SNV

Missense_Mutation

novel

c.128N>G

p.Phe43Cys

p.F43C

protein_coding

tolerated(0.15)

possibly_damaging(0.831)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

SDCBP

SNV

Missense_Mutation

novel

c.68C>A

p.Ser23Tyr

p.S23Y

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

SDCBP

SNV

Missense_Mutation

novel

c.125C>A

p.Ala42Asp

p.A42D

protein_coding

tolerated(0.22)

benign(0.287)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

SDCBP

SNV

Missense_Mutation

novel

c.16A>G

p.Thr6Ala

p.T6A

protein_coding

tolerated_low_confidence(1)

unknown(0)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SDCBP

SNV

Missense_Mutation

novel

c.220C>T

p.Leu74Phe

p.L74F

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-A5-A2K5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SDCBP

SNV

Missense_Mutation

novel

c.886N>A

p.Glu296Lys

p.E296K

protein_coding

tolerated(0.09)

benign(0.326)

TCGA-AJ-A3EK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

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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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