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: SH3PXD2A

Gene summary for SH3PXD2A

Gene summary.

Gene information	Species	Human
	Gene symbol	SH3PXD2A
	Gene ID	9644
	Gene name	SH3 and PX domains 2A
	Gene Alias	FISH
	Cytomap	10q24.33
	Gene Type	protein-coding
	GO ID	GO:0000768
	UniProtAcc	B3KPL1

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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
9644	SH3PXD2A	F034	Human	Colorectum	FAP	7.89e-16	-7.42e-03	-0.0665
9644	SH3PXD2A	F072B	Human	Colorectum	FAP	1.63e-10	3.09e-01	0.257
9644	SH3PXD2A	CRC-1-8810	Human	Colorectum	CRC	6.21e-05	-1.70e-01	0.6257
9644	SH3PXD2A	CRC-3-11773	Human	Colorectum	CRC	5.39e-11	-3.69e-01	0.2564
9644	SH3PXD2A	LZE4T	Human	Esophagus	ESCC	2.63e-08	1.25e-01	0.0811
9644	SH3PXD2A	LZE8T	Human	Esophagus	ESCC	2.96e-06	1.45e-01	0.067
9644	SH3PXD2A	LZE20T	Human	Esophagus	ESCC	2.84e-02	-7.11e-02	0.0662
9644	SH3PXD2A	LZE24T	Human	Esophagus	ESCC	9.62e-04	1.77e-01	0.0596
9644	SH3PXD2A	P1T-E	Human	Esophagus	ESCC	1.17e-10	2.77e-01	0.0875
9644	SH3PXD2A	P2T-E	Human	Esophagus	ESCC	9.64e-23	5.42e-01	0.1177
9644	SH3PXD2A	P4T-E	Human	Esophagus	ESCC	2.22e-13	2.41e-01	0.1323
9644	SH3PXD2A	P5T-E	Human	Esophagus	ESCC	4.68e-03	1.06e-01	0.1327
9644	SH3PXD2A	P8T-E	Human	Esophagus	ESCC	1.16e-06	1.75e-01	0.0889
9644	SH3PXD2A	P9T-E	Human	Esophagus	ESCC	5.93e-03	1.48e-01	0.1131
9644	SH3PXD2A	P10T-E	Human	Esophagus	ESCC	9.83e-06	1.34e-01	0.116
9644	SH3PXD2A	P11T-E	Human	Esophagus	ESCC	6.35e-15	9.68e-01	0.1426
9644	SH3PXD2A	P12T-E	Human	Esophagus	ESCC	5.67e-12	2.58e-01	0.1122
9644	SH3PXD2A	P15T-E	Human	Esophagus	ESCC	2.40e-21	3.68e-01	0.1149
9644	SH3PXD2A	P16T-E	Human	Esophagus	ESCC	1.61e-16	1.18e-01	0.1153
9644	SH3PXD2A	P20T-E	Human	Esophagus	ESCC	1.04e-12	4.02e-01	0.1124

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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
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:003009910	Cervix	CC	myeloid cell differentiation	83/2311	381/18723	1.31e-07	6.42e-06	83
GO:00025738	Cervix	CC	myeloid leukocyte differentiation	47/2311	208/18723	2.48e-05	4.27e-04	47
GO:00017018	Cervix	CC	in utero embryonic development	71/2311	367/18723	7.21e-05	1.00e-03	71
GO:00725939	Cervix	CC	reactive oxygen species metabolic process	47/2311	239/18723	7.74e-04	6.87e-03	47
GO:0000768	Cervix	CC	syncytium formation by plasma membrane fusion	15/2311	55/18723	2.14e-03	1.54e-02	15
GO:0140253	Cervix	CC	cell-cell fusion	15/2311	55/18723	2.14e-03	1.54e-02	15
GO:00069491	Cervix	CC	syncytium formation	15/2311	57/18723	3.13e-03	2.05e-02	15
GO:0006801	Cervix	CC	superoxide metabolic process	17/2311	74/18723	7.73e-03	4.10e-02	17
GO:0030316	Cervix	CC	osteoclast differentiation	20/2311	94/18723	9.92e-03	4.86e-02	20
GO:0030099	Colorectum	AD	myeloid cell differentiation	119/3918	381/18723	1.24e-06	4.01e-05	119
GO:0001701	Colorectum	AD	in utero embryonic development	110/3918	367/18723	2.36e-05	4.62e-04	110
GO:0072593	Colorectum	AD	reactive oxygen species metabolic process	73/3918	239/18723	2.79e-04	3.42e-03	73
GO:0002573	Colorectum	AD	myeloid leukocyte differentiation	60/3918	208/18723	4.03e-03	2.81e-02	60
GO:00725931	Colorectum	SER	reactive oxygen species metabolic process	61/2897	239/18723	3.63e-05	9.39e-04	61
GO:00300991	Colorectum	SER	myeloid cell differentiation	80/2897	381/18723	2.28e-03	2.18e-02	80
GO:00017011	Colorectum	SER	in utero embryonic development	77/2897	367/18723	2.77e-03	2.48e-02	77
GO:00017013	Colorectum	FAP	in utero embryonic development	81/2622	367/18723	1.58e-05	4.10e-04	81
GO:00300994	Colorectum	FAP	myeloid cell differentiation	81/2622	381/18723	6.33e-05	1.22e-03	81
GO:00300995	Colorectum	CRC	myeloid cell differentiation	66/2078	381/18723	1.59e-04	2.87e-03	66
GO:00025733	Colorectum	CRC	myeloid leukocyte differentiation	36/2078	208/18723	4.57e-03	3.57e-02	36

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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

SH3PXD2A

SNV

Missense_Mutation

novel

c.2608G>A

p.Glu870Lys

p.E870K

Q5TCZ1

protein_coding

tolerated(0.57)

benign(0.048)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

SH3PXD2A

SNV

Missense_Mutation

novel

c.739N>A

p.Gln247Lys

p.Q247K

Q5TCZ1

protein_coding

tolerated(0.12)

probably_damaging(0.946)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

SH3PXD2A

SNV

Missense_Mutation

c.1133C>G

p.Ser378Cys

p.S378C

Q5TCZ1

protein_coding

deleterious(0)

probably_damaging(0.988)

TCGA-AC-A2B8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

chemo

SH3PXD2A

SNV

Missense_Mutation

rs553552960

c.1090G>A

p.Val364Met

p.V364M

Q5TCZ1

protein_coding

tolerated(0.28)

benign(0.005)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

SH3PXD2A

SNV

Missense_Mutation

c.1996N>G

p.Ile666Val

p.I666V

Q5TCZ1

protein_coding

tolerated_low_confidence(0.43)

benign(0)

TCGA-BH-A0BT-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SH3PXD2A

SNV

Missense_Mutation

c.778N>C

p.Glu260Gln

p.E260Q

Q5TCZ1

protein_coding

deleterious(0)

possibly_damaging(0.844)

TCGA-C8-A12T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SH3PXD2A

SNV

Missense_Mutation

novel

c.1665N>C

p.Glu555Asp

p.E555D

Q5TCZ1

protein_coding

tolerated_low_confidence(0.49)

benign(0)

TCGA-C8-A8HP-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

5-fluorouracil

SH3PXD2A

SNV

Missense_Mutation

c.2421N>C

p.Lys807Asn

p.K807N

Q5TCZ1

protein_coding

tolerated(0.13)

benign(0.003)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

SH3PXD2A

SNV

Missense_Mutation

rs369836291

c.2981G>A

p.Arg994His

p.R994H

Q5TCZ1

protein_coding

tolerated(0.08)

possibly_damaging(0.674)

TCGA-E9-A295-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

SH3PXD2A

insertion

Frame_Shift_Ins

novel

c.2162_2163insCCAGCCAGGGT

p.Pro722GlnfsTer17

p.P722Qfs*17

Q5TCZ1

protein_coding

TCGA-AN-A0FS-01

Breast

breast invasive 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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