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: CWC25

Gene summary for CWC25

Gene summary.

Gene information	Species	Human
	Gene symbol	CWC25
	Gene ID	54883
	Gene name	CWC25 spliceosome associated protein homolog
	Gene Alias	CCDC49
	Cytomap	17q12
	Gene Type	protein-coding
	GO ID	GO:0000375
	UniProtAcc	Q9NXE8

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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
54883	CWC25	GSM4909290	Human	Breast	IDC	3.31e-46	9.95e-01	0.2096
54883	CWC25	GSM4909292	Human	Breast	IDC	1.12e-10	9.27e-01	0.1236
54883	CWC25	GSM4909293	Human	Breast	IDC	6.80e-45	7.66e-01	0.1581
54883	CWC25	GSM4909296	Human	Breast	IDC	1.38e-07	-1.87e-01	0.1524
54883	CWC25	GSM4909297	Human	Breast	IDC	6.54e-06	-6.13e-02	0.1517
54883	CWC25	GSM4909311	Human	Breast	IDC	9.06e-12	-1.67e-01	0.1534
54883	CWC25	GSM4909312	Human	Breast	IDC	2.86e-05	-6.06e-02	0.1552
54883	CWC25	GSM4909319	Human	Breast	IDC	1.20e-18	-1.03e-01	0.1563
54883	CWC25	GSM4909321	Human	Breast	IDC	4.28e-04	-5.28e-02	0.1559
54883	CWC25	P1	Human	Breast	IDC	1.02e-02	-1.08e-01	0.1527
54883	CWC25	DCIS2	Human	Breast	DCIS	4.88e-51	1.59e-01	0.0085
54883	CWC25	LZE3D	Human	Esophagus	HGIN	8.77e-04	4.00e-01	0.0668
54883	CWC25	LZE4T	Human	Esophagus	ESCC	2.96e-12	3.22e-01	0.0811
54883	CWC25	LZE7T	Human	Esophagus	ESCC	5.14e-12	3.79e-01	0.0667
54883	CWC25	LZE8T	Human	Esophagus	ESCC	1.43e-09	1.12e-01	0.067
54883	CWC25	LZE20T	Human	Esophagus	ESCC	1.38e-04	3.40e-02	0.0662
54883	CWC25	LZE21D1	Human	Esophagus	HGIN	1.21e-04	2.41e-01	0.0632
54883	CWC25	LZE22D1	Human	Esophagus	HGIN	1.62e-05	1.24e-01	0.0595
54883	CWC25	LZE22T	Human	Esophagus	ESCC	6.01e-04	1.78e-01	0.068
54883	CWC25	LZE24T	Human	Esophagus	ESCC	1.30e-16	5.14e-01	0.0596

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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
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:000838014	Breast	IDC	RNA splicing	73/1434	434/18723	1.27e-10	1.57e-08	73
GO:000037514	Breast	IDC	RNA splicing, via transesterification reactions	58/1434	324/18723	9.44e-10	9.58e-08	58
GO:000037714	Breast	IDC	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	57/1434	320/18723	1.60e-09	1.49e-07	57
GO:000039814	Breast	IDC	mRNA splicing, via spliceosome	57/1434	320/18723	1.60e-09	1.49e-07	57
GO:000838024	Breast	DCIS	RNA splicing	73/1390	434/18723	3.05e-11	5.08e-09	73
GO:000037524	Breast	DCIS	RNA splicing, via transesterification reactions	58/1390	324/18723	2.89e-10	3.34e-08	58
GO:000037724	Breast	DCIS	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	57/1390	320/18723	5.01e-10	5.35e-08	57
GO:000039824	Breast	DCIS	mRNA splicing, via spliceosome	57/1390	320/18723	5.01e-10	5.35e-08	57
GO:000838026	Esophagus	HGIN	RNA splicing	160/2587	434/18723	3.74e-34	1.12e-30	160
GO:000037520	Esophagus	HGIN	RNA splicing, via transesterification reactions	115/2587	324/18723	3.16e-23	3.80e-20	115
GO:000037720	Esophagus	HGIN	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	113/2587	320/18723	1.24e-22	9.26e-20	113
GO:000039820	Esophagus	HGIN	mRNA splicing, via spliceosome	113/2587	320/18723	1.24e-22	9.26e-20	113
GO:0008380111	Esophagus	ESCC	RNA splicing	336/8552	434/18723	1.74e-42	3.67e-39	336
GO:0000375111	Esophagus	ESCC	RNA splicing, via transesterification reactions	248/8552	324/18723	3.05e-30	1.49e-27	248
GO:0000377111	Esophagus	ESCC	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	244/8552	320/18723	2.52e-29	1.07e-26	244
GO:0000398111	Esophagus	ESCC	mRNA splicing, via spliceosome	244/8552	320/18723	2.52e-29	1.07e-26	244
GO:000838012	Liver	Cirrhotic	RNA splicing	229/4634	434/18723	9.13e-37	2.86e-33	229
GO:000037512	Liver	Cirrhotic	RNA splicing, via transesterification reactions	175/4634	324/18723	5.95e-30	7.47e-27	175
GO:000037712	Liver	Cirrhotic	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	172/4634	320/18723	4.02e-29	3.60e-26	172
GO:000039812	Liver	Cirrhotic	mRNA splicing, via spliceosome	172/4634	320/18723	4.02e-29	3.60e-26	172

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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

CWC25

SNV

Missense_Mutation

rs747456719

c.37C>A

p.His13Asn

p.H13N

Q9NXE8

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A8-A083-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CWC25

SNV

Missense_Mutation

rs747456719

c.37N>A

p.His13Asn

p.H13N

Q9NXE8

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A8-A095-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

CWC25

SNV

Missense_Mutation

rs747456719

c.37N>A

p.His13Asn

p.H13N

Q9NXE8

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AN-A0FV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CWC25

SNV

Missense_Mutation

rs555146635

c.187N>A

p.Val63Ile

p.V63I

Q9NXE8

protein_coding

tolerated(0.19)

benign(0.015)

TCGA-AR-A24N-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CWC25

SNV

Missense_Mutation

rs747456719

c.37N>A

p.His13Asn

p.H13N

Q9NXE8

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-B6-A0I9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

CWC25

SNV

Missense_Mutation

rs747456719

c.37N>A

p.His13Asn

p.H13N

Q9NXE8

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-B6-A0IA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CWC25

SNV

Missense_Mutation

rs747456719

c.37N>A

p.His13Asn

p.H13N

Q9NXE8

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-D8-A27M-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

methotrexate+5

CWC25

insertion

Nonsense_Mutation

novel

c.1018_1019insTCAAACCACCAGTGTTCAAAGTGACCCTGCTTCATTGAGTCCTGAAAC

p.Glu340delinsValLysProProValPheLysValThrLeuLeuHisTerValLeuLysGln

p.E340delinsVKPPVFKVTLLH*VLKQ

Q9NXE8

protein_coding

TCGA-A2-A0CQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

CWC25

deletion

In_Frame_Del

novel

c.37_63delNNNNNNNNNNNNNNNNNNNNNNNNNNN

p.His13_Glu21del

p.H13_E21del

Q9NXE8

protein_coding

TCGA-C8-A130-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

CWC25

deletion

Frame_Shift_Del

novel

c.467delA

p.Asn156IlefsTer3

p.N156Ifs*3

Q9NXE8

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

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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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