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: WNT2B

Gene summary for WNT2B

Gene summary.

Gene information	Species	Human
	Gene symbol	WNT2B
	Gene ID	7482
	Gene name	Wnt family member 2B
	Gene Alias	WNT13
	Cytomap	1p13.2
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q5TEH8

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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
7482	WNT2B	LZE4T	Human	Esophagus	ESCC	5.33e-03	1.51e-01	0.0811
7482	WNT2B	P1T-E	Human	Esophagus	ESCC	8.90e-04	1.82e-01	0.0875
7482	WNT2B	P5T-E	Human	Esophagus	ESCC	2.97e-04	1.21e-01	0.1327
7482	WNT2B	P9T-E	Human	Esophagus	ESCC	2.87e-09	2.19e-01	0.1131
7482	WNT2B	P10T-E	Human	Esophagus	ESCC	4.69e-06	8.59e-02	0.116
7482	WNT2B	P11T-E	Human	Esophagus	ESCC	1.17e-04	2.15e-01	0.1426
7482	WNT2B	P12T-E	Human	Esophagus	ESCC	1.82e-35	6.93e-01	0.1122
7482	WNT2B	P20T-E	Human	Esophagus	ESCC	1.86e-07	1.99e-01	0.1124
7482	WNT2B	P22T-E	Human	Esophagus	ESCC	3.75e-03	8.48e-02	0.1236
7482	WNT2B	P23T-E	Human	Esophagus	ESCC	1.82e-16	5.21e-01	0.108
7482	WNT2B	P26T-E	Human	Esophagus	ESCC	1.62e-16	3.10e-01	0.1276
7482	WNT2B	P27T-E	Human	Esophagus	ESCC	2.84e-17	2.03e-01	0.1055
7482	WNT2B	P28T-E	Human	Esophagus	ESCC	3.66e-25	5.72e-01	0.1149
7482	WNT2B	P30T-E	Human	Esophagus	ESCC	8.53e-15	7.06e-01	0.137
7482	WNT2B	P31T-E	Human	Esophagus	ESCC	1.75e-08	1.60e-01	0.1251
7482	WNT2B	P37T-E	Human	Esophagus	ESCC	2.98e-08	6.53e-02	0.1371
7482	WNT2B	P40T-E	Human	Esophagus	ESCC	3.22e-04	1.20e-01	0.109
7482	WNT2B	P42T-E	Human	Esophagus	ESCC	8.43e-06	2.05e-01	0.1175
7482	WNT2B	P48T-E	Human	Esophagus	ESCC	2.99e-10	2.11e-01	0.0959
7482	WNT2B	P49T-E	Human	Esophagus	ESCC	3.19e-03	3.83e-01	0.1768

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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:0071496111	Esophagus	ESCC	cellular response to external stimulus	215/8552	320/18723	4.29e-15	2.43e-13	215
GO:0031668111	Esophagus	ESCC	cellular response to extracellular stimulus	168/8552	246/18723	4.93e-13	2.23e-11	168
GO:0031669110	Esophagus	ESCC	cellular response to nutrient levels	148/8552	215/18723	4.58e-12	1.76e-10	148
GO:0031667111	Esophagus	ESCC	response to nutrient levels	289/8552	474/18723	9.25e-12	3.47e-10	289
GO:001605517	Esophagus	ESCC	Wnt signaling pathway	268/8552	444/18723	2.32e-10	6.58e-09	268
GO:019873817	Esophagus	ESCC	cell-cell signaling by wnt	269/8552	446/18723	2.41e-10	6.79e-09	269
GO:0009267110	Esophagus	ESCC	cellular response to starvation	110/8552	156/18723	2.63e-10	7.37e-09	110
GO:004259419	Esophagus	ESCC	response to starvation	133/8552	197/18723	4.31e-10	1.14e-08	133
GO:00163316	Esophagus	ESCC	morphogenesis of embryonic epithelium	98/8552	147/18723	2.12e-07	3.27e-06	98
GO:0061458110	Esophagus	ESCC	reproductive system development	247/8552	427/18723	2.24e-07	3.42e-06	247
GO:004860818	Esophagus	ESCC	reproductive structure development	245/8552	424/18723	2.82e-07	4.14e-06	245
GO:006007016	Esophagus	ESCC	canonical Wnt signaling pathway	180/8552	303/18723	9.15e-07	1.17e-05	180
GO:00303239	Esophagus	ESCC	respiratory tube development	112/8552	181/18723	7.82e-06	7.69e-05	112
GO:006056210	Esophagus	ESCC	epithelial tube morphogenesis	187/8552	325/18723	9.95e-06	9.44e-05	187
GO:00605417	Esophagus	ESCC	respiratory system development	123/8552	203/18723	1.26e-05	1.15e-04	123
GO:00303249	Esophagus	ESCC	lung development	109/8552	177/18723	1.40e-05	1.27e-04	109
GO:00604257	Esophagus	ESCC	lung morphogenesis	37/8552	50/18723	4.42e-05	3.51e-04	37
GO:00604414	Esophagus	ESCC	epithelial tube branching involved in lung morphogenesis	22/8552	29/18723	9.30e-04	4.73e-03	22
GO:00016559	Esophagus	ESCC	urogenital system development	177/8552	338/18723	7.51e-03	2.69e-02	177
GO:20000274	Esophagus	ESCC	regulation of animal organ morphogenesis	71/8552	125/18723	7.97e-03	2.84e-02	71

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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
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
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
WNT2B	FZD6_LRP5	WNT2B_FZD6_LRP5	WNT	Cervix	CC
WNT2B	FZD6_LRP6	WNT2B_FZD6_LRP6	WNT	Cervix	CC
WNT2B	FZD4_LRP6	WNT2B_FZD4_LRP6	WNT	Endometrium	AEH
WNT2B	FZD4_LRP6	WNT2B_FZD4_LRP6	WNT	Endometrium	EEC
WNT2B	FZD6_LRP6	WNT2B_FZD6_LRP6	WNT	Endometrium	EEC
WNT2B	FZD10_LRP6	WNT2B_FZD10_LRP6	WNT	Esophagus	ESCC
WNT2B	FZD3_LRP6	WNT2B_FZD3_LRP6	WNT	Esophagus	ESCC
WNT2B	FZD4_LRP6	WNT2B_FZD4_LRP6	WNT	Esophagus	ESCC
WNT2B	FZD5_LRP6	WNT2B_FZD5_LRP6	WNT	Esophagus	ESCC
WNT2B	FZD6_LRP6	WNT2B_FZD6_LRP6	WNT	Esophagus	ESCC
WNT2B	FZD8_LRP6	WNT2B_FZD8_LRP6	WNT	Esophagus	ESCC
WNT2B	FZD6_LRP5	WNT2B_FZD6_LRP5	WNT	HNSCC	Precancer
WNT2B	FZD6_LRP6	WNT2B_FZD6_LRP6	WNT	HNSCC	Precancer
WNT2B	FZD4_LRP5	WNT2B_FZD4_LRP5	WNT	Liver	Healthy
WNT2B	FZD6_LRP5	WNT2B_FZD6_LRP5	WNT	Liver	Healthy
WNT2B	FZD4_LRP6	WNT2B_FZD4_LRP6	WNT	Liver	Healthy
WNT2B	FZD6_LRP6	WNT2B_FZD6_LRP6	WNT	Liver	Healthy
WNT2B	FZD1_LRP5	WNT2B_FZD1_LRP5	WNT	THCA	Cancer
WNT2B	FZD4_LRP5	WNT2B_FZD4_LRP5	WNT	THCA	Cancer
WNT2B	FZD6_LRP5	WNT2B_FZD6_LRP5	WNT	THCA	Cancer

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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

WNT2B

SNV

Missense_Mutation

rs754142898

c.650T>C

p.Met217Thr

p.M217T

Q93097

protein_coding

deleterious(0)

probably_damaging(0.986)

TCGA-A8-A08L-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

WNT2B

SNV

Missense_Mutation

novel

c.651G>T

p.Met217Ile

p.M217I

Q93097

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-A8-A08L-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

WNT2B

SNV

Missense_Mutation

c.757N>T

p.Arg253Cys

p.R253C

Q93097

protein_coding

deleterious(0.01)

possibly_damaging(0.601)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

WNT2B

SNV

Missense_Mutation

rs140445206

c.302N>A

p.Arg101Gln

p.R101Q

Q93097

protein_coding

tolerated(0.21)

benign(0.041)

TCGA-B6-A0RI-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

WNT2B

SNV

Missense_Mutation

rs140255509

c.379N>A

p.Val127Ile

p.V127I

Q93097

protein_coding

deleterious(0.01)

benign(0.317)

TCGA-D8-A1JL-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WNT2B

SNV

Missense_Mutation

rs180824040

c.668N>A

p.Arg223His

p.R223H

Q93097

protein_coding

deleterious(0.03)

possibly_damaging(0.46)

TCGA-E9-A1NE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

WNT2B

insertion

Nonsense_Mutation

novel

c.1031_1032insAATATTTTAAATTGATGAGATAAAAAACATAGAAGTT

p.Tyr344Ter

p.Y344*

Q93097

protein_coding

TCGA-A2-A0EQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

WNT2B

SNV

Missense_Mutation

rs768030352

c.590G>A

p.Arg197His

p.R197H

Q93097

protein_coding

tolerated(0.1)

benign(0.066)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

WNT2B

SNV

Missense_Mutation

rs759333195

c.247C>T

p.Arg83Trp

p.R83W

Q93097

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-C5-A2M2-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

WNT2B

SNV

Missense_Mutation

c.335N>A

p.Arg112His

p.R112H

Q93097

protein_coding

deleterious(0.01)

probably_damaging(0.973)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

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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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