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: WNT5A

Gene summary for WNT5A

Gene summary.

Gene information	Species	Human
	Gene symbol	WNT5A
	Gene ID	7474
	Gene name	Wnt family member 5A
	Gene Alias	hWNT5A
	Cytomap	3p14.3
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	A0A024R316

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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
7474	WNT5A	LZE4T	Human	Esophagus	ESCC	1.47e-05	2.62e-01	0.0811
7474	WNT5A	P4T-E	Human	Esophagus	ESCC	1.29e-08	3.40e-01	0.1323
7474	WNT5A	P8T-E	Human	Esophagus	ESCC	9.35e-12	2.41e-01	0.0889
7474	WNT5A	P9T-E	Human	Esophagus	ESCC	7.73e-07	2.00e-01	0.1131
7474	WNT5A	P10T-E	Human	Esophagus	ESCC	7.80e-11	2.40e-01	0.116
7474	WNT5A	P12T-E	Human	Esophagus	ESCC	2.33e-33	6.94e-01	0.1122
7474	WNT5A	P15T-E	Human	Esophagus	ESCC	6.29e-13	3.25e-01	0.1149
7474	WNT5A	P22T-E	Human	Esophagus	ESCC	6.11e-04	1.56e-01	0.1236
7474	WNT5A	P23T-E	Human	Esophagus	ESCC	5.15e-05	3.79e-01	0.108
7474	WNT5A	P24T-E	Human	Esophagus	ESCC	7.66e-05	2.02e-01	0.1287
7474	WNT5A	P26T-E	Human	Esophagus	ESCC	1.93e-16	3.97e-01	0.1276
7474	WNT5A	P27T-E	Human	Esophagus	ESCC	6.39e-18	3.45e-01	0.1055
7474	WNT5A	P28T-E	Human	Esophagus	ESCC	4.38e-05	7.38e-02	0.1149
7474	WNT5A	P30T-E	Human	Esophagus	ESCC	3.26e-21	9.54e-01	0.137
7474	WNT5A	P32T-E	Human	Esophagus	ESCC	9.60e-09	2.51e-01	0.1666
7474	WNT5A	P36T-E	Human	Esophagus	ESCC	4.78e-07	3.85e-01	0.1187
7474	WNT5A	P39T-E	Human	Esophagus	ESCC	2.79e-12	2.82e-01	0.0894
7474	WNT5A	P42T-E	Human	Esophagus	ESCC	4.51e-07	4.71e-01	0.1175
7474	WNT5A	P47T-E	Human	Esophagus	ESCC	1.69e-02	2.39e-01	0.1067
7474	WNT5A	P48T-E	Human	Esophagus	ESCC	6.01e-11	2.86e-01	0.0959

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
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:004858810	Esophagus	ESCC	developmental cell growth	125/8552	234/18723	1.01e-02	3.46e-02	125
GO:00463302	Esophagus	ESCC	positive regulation of JNK cascade	52/8552	89/18723	1.04e-02	3.56e-02	52
GO:00017639	Esophagus	ESCC	morphogenesis of a branching structure	106/8552	196/18723	1.08e-02	3.66e-02	106
GO:00512161	Esophagus	ESCC	cartilage development	103/8552	190/18723	1.08e-02	3.67e-02	103
GO:001821010	Esophagus	ESCC	peptidyl-threonine modification	70/8552	125/18723	1.29e-02	4.25e-02	70
GO:001470615	Esophagus	ESCC	striated muscle tissue development	197/8552	384/18723	1.46e-02	4.74e-02	197
GO:0070231	Esophagus	ESCC	T cell apoptotic process	31/8552	50/18723	1.48e-02	4.79e-02	31
GO:00104645	Esophagus	ESCC	regulation of mesenchymal cell proliferation	19/8552	28/18723	1.49e-02	4.84e-02	19
GO:190188810	Esophagus	ESCC	regulation of cell junction assembly	109/8552	204/18723	1.53e-02	4.96e-02	109
GO:00331383	Esophagus	ESCC	positive regulation of peptidyl-serine phosphorylation	61/8552	108/18723	1.54e-02	4.96e-02	61
GO:0009896113	Thyroid	PTC	positive regulation of catabolic process	278/5968	492/18723	3.35e-30	2.64e-27	278
GO:0042176113	Thyroid	PTC	regulation of protein catabolic process	231/5968	391/18723	4.76e-29	2.14e-26	231
GO:0045732113	Thyroid	PTC	positive regulation of protein catabolic process	142/5968	231/18723	1.43e-20	2.38e-18	142
GO:0051098113	Thyroid	PTC	regulation of binding	195/5968	363/18723	3.21e-18	3.37e-16	195
GO:0022604112	Thyroid	PTC	regulation of cell morphogenesis	165/5968	309/18723	2.60e-15	1.82e-13	165
GO:0016055110	Thyroid	PTC	Wnt signaling pathway	217/5968	444/18723	3.71e-14	2.30e-12	217
GO:0198738110	Thyroid	PTC	cell-cell signaling by wnt	217/5968	446/18723	6.68e-14	3.73e-12	217
GO:0051099113	Thyroid	PTC	positive regulation of binding	100/5968	173/18723	1.56e-12	6.96e-11	100
GO:0016049112	Thyroid	PTC	cell growth	225/5968	482/18723	4.75e-12	2.07e-10	225
GO:0030111110	Thyroid	PTC	regulation of Wnt signaling pathway	163/5968	328/18723	1.05e-11	4.29e-10	163

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05022210	Esophagus	ESCC	Pathways of neurodegeneration - multiple diseases	318/4205	476/8465	6.10e-15	2.04e-13	1.05e-13	318
hsa05010210	Esophagus	ESCC	Alzheimer disease	263/4205	384/8465	1.80e-14	5.47e-13	2.80e-13	263
hsa0516510	Esophagus	ESCC	Human papillomavirus infection	215/4205	331/8465	7.86e-09	7.12e-08	3.65e-08	215
hsa0520529	Esophagus	ESCC	Proteoglycans in cancer	138/4205	205/8465	1.79e-07	1.40e-06	7.15e-07	138
hsa0522518	Esophagus	ESCC	Hepatocellular carcinoma	109/4205	168/8465	4.27e-05	1.88e-04	9.64e-05	109
hsa041505	Esophagus	ESCC	mTOR signaling pathway	98/4205	156/8465	5.81e-04	1.95e-03	9.97e-04	98
hsa0436016	Esophagus	ESCC	Axon guidance	108/4205	182/8465	5.13e-03	1.30e-02	6.67e-03	108
hsa0439018	Esophagus	ESCC	Hippo signaling pathway	92/4205	157/8465	1.46e-02	3.31e-02	1.69e-02	92
hsa0502238	Esophagus	ESCC	Pathways of neurodegeneration - multiple diseases	318/4205	476/8465	6.10e-15	2.04e-13	1.05e-13	318
hsa0501038	Esophagus	ESCC	Alzheimer disease	263/4205	384/8465	1.80e-14	5.47e-13	2.80e-13	263
hsa0516515	Esophagus	ESCC	Human papillomavirus infection	215/4205	331/8465	7.86e-09	7.12e-08	3.65e-08	215
hsa0520537	Esophagus	ESCC	Proteoglycans in cancer	138/4205	205/8465	1.79e-07	1.40e-06	7.15e-07	138
hsa0522519	Esophagus	ESCC	Hepatocellular carcinoma	109/4205	168/8465	4.27e-05	1.88e-04	9.64e-05	109
hsa0415013	Esophagus	ESCC	mTOR signaling pathway	98/4205	156/8465	5.81e-04	1.95e-03	9.97e-04	98
hsa0436017	Esophagus	ESCC	Axon guidance	108/4205	182/8465	5.13e-03	1.30e-02	6.67e-03	108
hsa0439019	Esophagus	ESCC	Hippo signaling pathway	92/4205	157/8465	1.46e-02	3.31e-02	1.69e-02	92

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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
WNT5A	FZD1	WNT5A_FZD1	ncWNT	Cervix	ADJ
WNT5A	FZD4	WNT5A_FZD4	ncWNT	Cervix	ADJ
WNT5A	FZD6	WNT5A_FZD6	ncWNT	Cervix	ADJ
WNT5A	FZD7	WNT5A_FZD7	ncWNT	Cervix	ADJ
WNT5A	MCAM	WNT5A_MCAM	ncWNT	Cervix	ADJ
WNT5A	FZD4	WNT5A_FZD4	ncWNT	Cervix	CC
WNT5A	FZD6	WNT5A_FZD6	ncWNT	Cervix	CC
WNT5A	MCAM	WNT5A_MCAM	ncWNT	Cervix	CC
WNT5A	MCAM	WNT5A_MCAM	ncWNT	Cervix	Precancer
WNT5A	FZD4	WNT5A_FZD4	ncWNT	Endometrium	ADJ
WNT5A	FZD6	WNT5A_FZD6	ncWNT	Endometrium	ADJ
WNT5A	MCAM	WNT5A_MCAM	ncWNT	Endometrium	ADJ
WNT5A	FZD4	WNT5A_FZD4	ncWNT	Endometrium	AEH
WNT5A	FZD7	WNT5A_FZD7	ncWNT	Endometrium	AEH
WNT5A	MCAM	WNT5A_MCAM	ncWNT	Endometrium	AEH
WNT5A	MCAM	WNT5A_MCAM	ncWNT	Endometrium	Healthy
WNT5A	FZD1	WNT5A_FZD1	ncWNT	Esophagus	ESCC
WNT5A	FZD10	WNT5A_FZD10	ncWNT	Esophagus	ESCC
WNT5A	FZD3	WNT5A_FZD3	ncWNT	Esophagus	ESCC
WNT5A	FZD4	WNT5A_FZD4	ncWNT	Esophagus	ESCC

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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

WNT5A

SNV

Missense_Mutation

rs369954366

c.830G>A

p.Arg277Gln

p.R277Q

P41221

protein_coding

tolerated(0.05)

possibly_damaging(0.65)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

WNT5A

SNV

Missense_Mutation

novel

c.947N>A

p.Gly316Asp

p.G316D

P41221

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-C5-A1M6-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

WNT5A

SNV

Missense_Mutation

rs755298573

c.1055N>T

p.Thr352Met

p.T352M

P41221

protein_coding

tolerated(0.09)

possibly_damaging(0.502)

TCGA-UC-A7PI-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

WNT5A

SNV

Missense_Mutation

c.758G>T

p.Trp253Leu

p.W253L

P41221

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AA-3489-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

WNT5A

SNV

Missense_Mutation

c.442N>T

p.Asn148Tyr

p.N148Y

P41221

protein_coding

tolerated(1)

possibly_damaging(0.629)

TCGA-AA-3492-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

WNT5A

SNV

Missense_Mutation

rs201975128

c.983N>T

p.Thr328Met

p.T328M

P41221

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-AA-3947-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

WNT5A

SNV

Missense_Mutation

c.928N>A

p.Val310Met

p.V310M

P41221

protein_coding

tolerated(0.13)

benign(0.051)

TCGA-AA-3984-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

WNT5A

SNV

Missense_Mutation

c.306A>C

p.Lys102Asn

p.K102N

P41221

protein_coding

tolerated(0.1)

possibly_damaging(0.529)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

WNT5A

SNV

Missense_Mutation

c.1021N>T

p.Gly341Cys

p.G341C

P41221

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AA-A02R-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

WNT5A

SNV

Missense_Mutation

c.928N>A

p.Val310Met

p.V310M

P41221

protein_coding

tolerated(0.13)

benign(0.051)

TCGA-AM-5821-01

Colorectum

colon adenocarcinoma

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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