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: PXN

Gene summary for PXN

Gene summary.

Gene information	Species	Human
	Gene symbol	PXN
	Gene ID	5829
	Gene name	paxillin
	Gene Alias	PXN
	Cytomap	12q24.23
	Gene Type	protein-coding
	GO ID	GO:0000302
	UniProtAcc	A0A140VJQ8

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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
5829	PXN	HTA11_2487_2000001011	Human	Colorectum	SER	7.83e-03	3.82e-01	-0.1808
5829	PXN	HTA11_78_2000001011	Human	Colorectum	AD	3.93e-03	3.77e-01	-0.1088
5829	PXN	HTA11_347_2000001011	Human	Colorectum	AD	3.51e-14	5.84e-01	-0.1954
5829	PXN	HTA11_696_2000001011	Human	Colorectum	AD	7.69e-04	3.13e-01	-0.1464
5829	PXN	HTA11_866_2000001011	Human	Colorectum	AD	1.05e-02	2.92e-01	-0.1001
5829	PXN	A015-C-203	Human	Colorectum	FAP	4.49e-04	-9.19e-02	-0.1294
5829	PXN	A002-C-205	Human	Colorectum	FAP	2.26e-05	-2.33e-01	-0.1236
5829	PXN	A015-C-104	Human	Colorectum	FAP	4.73e-06	-1.07e-01	-0.1899
5829	PXN	A002-C-016	Human	Colorectum	FAP	8.81e-06	-1.80e-01	0.0521
5829	PXN	A002-C-116	Human	Colorectum	FAP	3.78e-11	-2.04e-01	-0.0452
5829	PXN	F034	Human	Colorectum	FAP	2.87e-05	-1.85e-01	-0.0665
5829	PXN	F072B	Human	Colorectum	FAP	2.94e-03	-1.77e-01	0.257
5829	PXN	LZE4T	Human	Esophagus	ESCC	4.28e-08	-1.01e-01	0.0811
5829	PXN	LZE7T	Human	Esophagus	ESCC	2.23e-04	-9.42e-03	0.0667
5829	PXN	LZE8T	Human	Esophagus	ESCC	8.23e-05	2.36e-02	0.067
5829	PXN	LZE20T	Human	Esophagus	ESCC	4.81e-04	-8.51e-02	0.0662
5829	PXN	LZE22D1	Human	Esophagus	HGIN	6.59e-03	-9.25e-02	0.0595
5829	PXN	LZE24T	Human	Esophagus	ESCC	9.31e-10	1.76e-02	0.0596
5829	PXN	LZE6T	Human	Esophagus	ESCC	3.02e-02	1.31e-01	0.0845
5829	PXN	P2T-E	Human	Esophagus	ESCC	1.24e-25	5.04e-01	0.1177

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0007015	Colorectum	AD	actin filament organization	167/3918	442/18723	1.65e-16	7.94e-14	167
GO:1902903	Colorectum	AD	regulation of supramolecular fiber organization	139/3918	383/18723	2.01e-12	3.19e-10	139
GO:0032970	Colorectum	AD	regulation of actin filament-based process	142/3918	397/18723	4.05e-12	5.90e-10	142
GO:0110053	Colorectum	AD	regulation of actin filament organization	108/3918	278/18723	5.02e-12	6.98e-10	108
GO:1902905	Colorectum	AD	positive regulation of supramolecular fiber organization	85/3918	209/18723	5.95e-11	6.33e-09	85
GO:0032956	Colorectum	AD	regulation of actin cytoskeleton organization	127/3918	358/18723	1.03e-10	1.04e-08	127
GO:0051495	Colorectum	AD	positive regulation of cytoskeleton organization	89/3918	226/18723	1.61e-10	1.56e-08	89
GO:0006979	Colorectum	AD	response to oxidative stress	145/3918	446/18723	5.16e-09	3.23e-07	145
GO:0031589	Colorectum	AD	cell-substrate adhesion	116/3918	363/18723	4.68e-07	1.76e-05	116
GO:0062197	Colorectum	AD	cellular response to chemical stress	109/3918	337/18723	5.33e-07	1.95e-05	109
GO:0000302	Colorectum	AD	response to reactive oxygen species	78/3918	222/18723	6.17e-07	2.21e-05	78
GO:1901653	Colorectum	AD	cellular response to peptide	114/3918	359/18723	8.32e-07	2.88e-05	114
GO:0061572	Colorectum	AD	actin filament bundle organization	60/3918	161/18723	1.33e-06	4.23e-05	60
GO:0071375	Colorectum	AD	cellular response to peptide hormone stimulus	95/3918	290/18723	1.50e-06	4.66e-05	95
GO:0034599	Colorectum	AD	cellular response to oxidative stress	94/3918	288/18723	2.03e-06	6.02e-05	94
GO:0043434	Colorectum	AD	response to peptide hormone	126/3918	414/18723	2.70e-06	7.86e-05	126
GO:0051017	Colorectum	AD	actin filament bundle assembly	58/3918	157/18723	2.74e-06	7.89e-05	58
GO:0001667	Colorectum	AD	ameboidal-type cell migration	137/3918	475/18723	2.17e-05	4.33e-04	137
GO:0007160	Colorectum	AD	cell-matrix adhesion	75/3918	233/18723	3.56e-05	6.45e-04	75
GO:0031032	Colorectum	AD	actomyosin structure organization	65/3918	196/18723	4.17e-05	7.37e-04	65

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05131	Colorectum	AD	Shigellosis	109/2092	247/8465	1.09e-11	2.44e-10	1.55e-10	109
hsa05100	Colorectum	AD	Bacterial invasion of epithelial cells	44/2092	77/8465	1.13e-09	2.22e-08	1.42e-08	44
hsa05135	Colorectum	AD	Yersinia infection	58/2092	137/8465	3.90e-06	4.35e-05	2.78e-05	58
hsa05205	Colorectum	AD	Proteoglycans in cancer	70/2092	205/8465	1.37e-03	8.46e-03	5.39e-03	70
hsa05170	Colorectum	AD	Human immunodeficiency virus 1 infection	72/2092	212/8465	1.40e-03	8.46e-03	5.39e-03	72
hsa05163	Colorectum	AD	Human cytomegalovirus infection	75/2092	225/8465	2.00e-03	1.10e-02	7.01e-03	75
hsa04810	Colorectum	AD	Regulation of actin cytoskeleton	75/2092	229/8465	3.36e-03	1.76e-02	1.12e-02	75
hsa04510	Colorectum	AD	Focal adhesion	67/2092	203/8465	4.40e-03	2.17e-02	1.38e-02	67
hsa04670	Colorectum	AD	Leukocyte transendothelial migration	41/2092	114/8465	4.60e-03	2.20e-02	1.40e-02	41
hsa051311	Colorectum	AD	Shigellosis	109/2092	247/8465	1.09e-11	2.44e-10	1.55e-10	109
hsa051001	Colorectum	AD	Bacterial invasion of epithelial cells	44/2092	77/8465	1.13e-09	2.22e-08	1.42e-08	44
hsa051351	Colorectum	AD	Yersinia infection	58/2092	137/8465	3.90e-06	4.35e-05	2.78e-05	58
hsa052051	Colorectum	AD	Proteoglycans in cancer	70/2092	205/8465	1.37e-03	8.46e-03	5.39e-03	70
hsa051701	Colorectum	AD	Human immunodeficiency virus 1 infection	72/2092	212/8465	1.40e-03	8.46e-03	5.39e-03	72
hsa051631	Colorectum	AD	Human cytomegalovirus infection	75/2092	225/8465	2.00e-03	1.10e-02	7.01e-03	75
hsa048101	Colorectum	AD	Regulation of actin cytoskeleton	75/2092	229/8465	3.36e-03	1.76e-02	1.12e-02	75
hsa045101	Colorectum	AD	Focal adhesion	67/2092	203/8465	4.40e-03	2.17e-02	1.38e-02	67
hsa046701	Colorectum	AD	Leukocyte transendothelial migration	41/2092	114/8465	4.60e-03	2.20e-02	1.40e-02	41
hsa051312	Colorectum	SER	Shigellosis	87/1580	247/8465	3.07e-10	7.27e-09	5.28e-09	87
hsa051002	Colorectum	SER	Bacterial invasion of epithelial cells	36/1580	77/8465	1.56e-08	3.45e-07	2.50e-07	36

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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

PXN

SNV

Missense_Mutation

c.1190N>C

p.Val397Ala

p.V397A

P49023

protein_coding

deleterious(0.01)

possibly_damaging(0.544)

TCGA-WS-AB45-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

PXN

SNV

Missense_Mutation

c.402N>T

p.Met134Ile

p.M134I

P49023

protein_coding

tolerated(0.06)

benign(0.318)

TCGA-AJ-A3EL-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PXN

SNV

Missense_Mutation

novel

c.382N>A

p.Glu128Lys

p.E128K

P49023

protein_coding

tolerated(0.09)

possibly_damaging(0.571)

TCGA-AJ-A3TW-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

PXN

SNV

Missense_Mutation

rs201921559

c.740N>A

p.Arg247His

p.R247H

P49023

protein_coding

tolerated(0.08)

benign(0.027)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

PXN

SNV

Missense_Mutation

rs750675975

c.611N>A

p.Arg204Gln

p.R204Q

P49023

protein_coding

deleterious(0.03)

possibly_damaging(0.515)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

PXN

SNV

Missense_Mutation

c.1735N>A

p.Leu579Ile

p.L579I

P49023

protein_coding

deleterious(0)

probably_damaging(0.954)

TCGA-B5-A11E-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PXN

SNV

Missense_Mutation

novel

c.862C>T

p.Leu288Phe

p.L288F

P49023

protein_coding

tolerated(0.37)

benign(0.046)

TCGA-B5-A1MX-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Hormone Therapy

megace

PXN

SNV

Missense_Mutation

rs372866217

c.1436N>A

p.Arg479His

p.R479H

P49023

protein_coding

deleterious(0)

possibly_damaging(0.576)

TCGA-BS-A0UF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

PXN

SNV

Missense_Mutation

novel

c.1399G>A

p.Glu467Lys

p.E467K

P49023

protein_coding

deleterious(0)

probably_damaging(0.964)

TCGA-D1-A16Y-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PXN

SNV

Missense_Mutation

c.1688N>T

p.Ala563Val

p.A563V

P49023

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-D1-A17H-01

Endometrium

uterine corpus endometrioid 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
5829	PXN	NA		H2O2		9590268
5829	PXN	NA		1,2,4,5-BENZENETETRAAMINE TETRAHYDROCHLORIDE	CHEMBL456559	18989950
5829	PXN	NA		ANTISENSE OLIGONUCLEOTIDES		14576084
5829	PXN	NA		LOVASTATIN	LOVASTATIN	11581207

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