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:00160503	Colorectum	FAP	vesicle organization	74/2622	300/18723	5.16e-07	2.66e-05	74
GO:00459273	Colorectum	FAP	positive regulation of growth	66/2622	259/18723	6.11e-07	3.05e-05	66
GO:00421774	Colorectum	FAP	negative regulation of protein catabolic process	38/2622	121/18723	7.10e-07	3.32e-05	38
GO:00072652	Colorectum	FAP	Ras protein signal transduction	80/2622	337/18723	9.61e-07	4.33e-05	80
GO:00068982	Colorectum	FAP	receptor-mediated endocytosis	62/2622	244/18723	1.47e-06	6.39e-05	62
GO:00431122	Colorectum	FAP	receptor metabolic process	46/2622	166/18723	2.70e-06	1.02e-04	46
GO:00066054	Colorectum	FAP	protein targeting	74/2622	314/18723	3.21e-06	1.17e-04	74
GO:00715591	Colorectum	FAP	response to transforming growth factor beta	63/2622	256/18723	3.82e-06	1.32e-04	63
GO:00071782	Colorectum	FAP	transmembrane receptor protein serine/threonine kinase signaling pathway	81/2622	355/18723	4.28e-06	1.46e-04	81
GO:00310983	Colorectum	FAP	stress-activated protein kinase signaling cascade	61/2622	247/18723	4.79e-06	1.57e-04	61
GO:00303073	Colorectum	FAP	positive regulation of cell growth	45/2622	166/18723	6.49e-06	2.02e-04	45
GO:00514033	Colorectum	FAP	stress-activated MAPK cascade	59/2622	239/18723	6.90e-06	2.11e-04	59
GO:00715601	Colorectum	FAP	cellular response to transforming growth factor beta stimulus	61/2622	250/18723	7.22e-06	2.19e-04	61
GO:19033634	Colorectum	FAP	negative regulation of cellular protein catabolic process	25/2622	75/18723	1.74e-05	4.42e-04	25
GO:00071791	Colorectum	FAP	transforming growth factor beta receptor signaling pathway	50/2622	198/18723	1.75e-05	4.44e-04	50
GO:00508083	Colorectum	FAP	synapse organization	91/2622	426/18723	1.90e-05	4.74e-04	91
GO:19030504	Colorectum	FAP	regulation of proteolysis involved in cellular protein catabolic process	54/2622	221/18723	2.26e-05	5.32e-04	54
GO:00301003	Colorectum	FAP	regulation of endocytosis	52/2622	211/18723	2.47e-05	5.77e-04	52
GO:00703022	Colorectum	FAP	regulation of stress-activated protein kinase signaling cascade	48/2622	195/18723	5.14e-05	1.04e-03	48
GO:00328722	Colorectum	FAP	regulation of stress-activated MAPK cascade	47/2622	192/18723	7.08e-05	1.32e-03	47

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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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