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: SORBS2

Gene summary for SORBS2

Gene summary.

Gene information	Species	Human
	Gene symbol	SORBS2
	Gene ID	8470
	Gene name	sorbin and SH3 domain containing 2
	Gene Alias	ARGBP2
	Cytomap	4q35.1
	Gene Type	protein-coding
	GO ID	GO:0003008
	UniProtAcc	O94875

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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
8470	SORBS2	GSM4909281	Human	Breast	IDC	5.03e-03	2.77e-01	0.21
8470	SORBS2	GSM4909286	Human	Breast	IDC	2.02e-02	-8.44e-02	0.1081
8470	SORBS2	GSM4909297	Human	Breast	IDC	4.61e-09	-3.01e-01	0.1517
8470	SORBS2	GSM4909299	Human	Breast	IDC	6.34e-09	4.93e-01	0.035
8470	SORBS2	GSM4909300	Human	Breast	IDC	2.03e-02	4.61e-01	0.0334
8470	SORBS2	GSM4909304	Human	Breast	IDC	2.16e-08	-3.15e-01	0.1636
8470	SORBS2	GSM4909307	Human	Breast	IDC	3.14e-05	4.15e-01	0.1569
8470	SORBS2	GSM4909308	Human	Breast	IDC	1.51e-14	5.74e-01	0.158
8470	SORBS2	GSM4909309	Human	Breast	IDC	1.20e-06	4.81e-01	0.0483
8470	SORBS2	GSM4909311	Human	Breast	IDC	7.36e-11	-2.55e-01	0.1534
8470	SORBS2	GSM4909315	Human	Breast	IDC	2.44e-15	-3.35e-01	0.21
8470	SORBS2	GSM4909316	Human	Breast	IDC	2.46e-04	-3.40e-01	0.21
8470	SORBS2	GSM4909319	Human	Breast	IDC	4.11e-12	-3.27e-01	0.1563
8470	SORBS2	GSM4909320	Human	Breast	IDC	3.15e-05	-3.40e-01	0.1575
8470	SORBS2	GSM4909321	Human	Breast	IDC	6.69e-11	-2.77e-01	0.1559
8470	SORBS2	brca10	Human	Breast	Precancer	2.02e-08	-2.85e-01	-0.0029
8470	SORBS2	NCCBC14	Human	Breast	DCIS	8.16e-07	-1.58e-01	0.2021
8470	SORBS2	NCCBC5	Human	Breast	DCIS	2.24e-09	-3.12e-01	0.2046
8470	SORBS2	P1	Human	Breast	IDC	2.89e-07	-2.44e-01	0.1527
8470	SORBS2	P2	Human	Breast	IDC	2.03e-05	-3.10e-01	0.21

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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
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
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:00070159	Breast	Precancer	actin filament organization	44/1080	442/18723	3.02e-04	4.35e-03	44
GO:00160497	Breast	Precancer	cell growth	46/1080	482/18723	5.63e-04	7.16e-03	46
GO:00605374	Breast	Precancer	muscle tissue development	37/1080	403/18723	3.60e-03	2.98e-02	37
GO:00147063	Breast	Precancer	striated muscle tissue development	35/1080	384/18723	5.10e-03	3.83e-02	35
GO:000701514	Breast	IDC	actin filament organization	55/1434	442/18723	2.45e-04	3.84e-03	55
GO:006053711	Breast	IDC	muscle tissue development	50/1434	403/18723	4.91e-04	6.45e-03	50
GO:001604913	Breast	IDC	cell growth	56/1434	482/18723	1.16e-03	1.26e-02	56
GO:00147061	Breast	IDC	striated muscle tissue development	46/1434	384/18723	1.67e-03	1.63e-02	46
GO:00426923	Breast	IDC	muscle cell differentiation	44/1434	384/18723	4.77e-03	3.66e-02	44
GO:00030125	Breast	IDC	muscle system process	50/1434	452/18723	5.52e-03	4.05e-02	50
GO:00511463	Breast	IDC	striated muscle cell differentiation	34/1434	283/18723	6.00e-03	4.31e-02	34
GO:000701524	Breast	DCIS	actin filament organization	56/1390	442/18723	5.90e-05	1.19e-03	56
GO:006053721	Breast	DCIS	muscle tissue development	50/1390	403/18723	2.39e-04	3.74e-03	50
GO:00147062	Breast	DCIS	striated muscle tissue development	46/1390	384/18723	8.88e-04	1.01e-02	46
GO:001604923	Breast	DCIS	cell growth	54/1390	482/18723	1.60e-03	1.59e-02	54
GO:000301212	Breast	DCIS	muscle system process	50/1390	452/18723	3.02e-03	2.57e-02	50
GO:004269211	Breast	DCIS	muscle cell differentiation	43/1390	384/18723	4.56e-03	3.49e-02	43
GO:005114611	Breast	DCIS	striated muscle cell differentiation	33/1390	283/18723	6.63e-03	4.62e-02	33
GO:0007015	Colorectum	AD	actin filament organization	167/3918	442/18723	1.65e-16	7.94e-14	167
GO:0016049	Colorectum	AD	cell growth	143/3918	482/18723	2.83e-06	8.09e-05	143

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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

SORBS2

SNV

Missense_Mutation

c.2713N>A

p.Cys905Ser

p.C905S

O94875

protein_coding

tolerated(0.33)

benign(0.06)

TCGA-A2-A0SV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate therapy

zometa

SORBS2

SNV

Missense_Mutation

novel

c.1742A>G

p.Glu581Gly

p.E581G

O94875

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A2-A1FZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Arimidex

SORBS2

SNV

Missense_Mutation

c.1954N>C

p.Glu652Gln

p.E652Q

O94875

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A8-A081-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SORBS2

SNV

Missense_Mutation

c.481G>C

p.Glu161Gln

p.E161Q

O94875

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A8-A08L-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

SORBS2

SNV

Missense_Mutation

novel

c.2567T>C

p.Ile856Thr

p.I856T

O94875

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SORBS2

SNV

Missense_Mutation

c.2435C>T

p.Ser812Leu

p.S812L

O94875

protein_coding

tolerated(0.3)

benign(0)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SORBS2

SNV

Missense_Mutation

c.3505G>A

p.Asp1169Asn

p.D1169N

O94875

protein_coding

deleterious(0.01)

probably_damaging(0.925)

TCGA-BH-A0DZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

SORBS2

SNV

Missense_Mutation

c.1739N>G

p.Tyr580Cys

p.Y580C

O94875

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-D8-A1Y0-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cyclophosphamide+methotrexatum+fluorouracillum

SORBS2

SNV

Missense_Mutation

novel

c.290C>T

p.Ala97Val

p.A97V

O94875

protein_coding

tolerated(0.05)

benign(0.279)

TCGA-OL-A6VR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SORBS2

insertion

Frame_Shift_Ins

novel

c.2542_2543insTGCCCCGCAGTGCCTCTTTCCAAGACGTGGACACAGCCAACAGCAGC

p.Arg848MetfsTer44

p.R848Mfs*44

O94875

protein_coding

TCGA-A2-A0EQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

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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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