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: CSDE1

Gene summary for CSDE1

Gene summary.

Gene information	Species	Human
	Gene symbol	CSDE1
	Gene ID	7812
	Gene name	cold shock domain containing E1
	Gene Alias	D1S155E
	Cytomap	1p13.2
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	A0A024R0E2

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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
7812	CSDE1	GSM4909286	Human	Breast	IDC	1.92e-05	-2.50e-01	0.1081
7812	CSDE1	GSM4909294	Human	Breast	IDC	3.74e-14	-4.34e-02	0.2022
7812	CSDE1	GSM4909296	Human	Breast	IDC	1.20e-20	-3.60e-01	0.1524
7812	CSDE1	GSM4909297	Human	Breast	IDC	5.66e-19	-3.61e-01	0.1517
7812	CSDE1	GSM4909301	Human	Breast	IDC	1.55e-14	-4.83e-01	0.1577
7812	CSDE1	GSM4909302	Human	Breast	IDC	5.50e-06	-4.06e-01	0.1545
7812	CSDE1	GSM4909304	Human	Breast	IDC	2.90e-02	-1.96e-01	0.1636
7812	CSDE1	GSM4909306	Human	Breast	IDC	1.99e-09	-3.92e-01	0.1564
7812	CSDE1	GSM4909307	Human	Breast	IDC	2.04e-16	-4.90e-01	0.1569
7812	CSDE1	GSM4909308	Human	Breast	IDC	8.86e-07	-4.44e-01	0.158
7812	CSDE1	GSM4909311	Human	Breast	IDC	2.58e-49	-4.66e-01	0.1534
7812	CSDE1	GSM4909312	Human	Breast	IDC	9.56e-14	-4.55e-04	0.1552
7812	CSDE1	GSM4909313	Human	Breast	IDC	6.56e-03	-4.31e-04	0.0391
7812	CSDE1	GSM4909319	Human	Breast	IDC	1.64e-56	-6.99e-01	0.1563
7812	CSDE1	GSM4909320	Human	Breast	IDC	1.93e-14	-7.61e-01	0.1575
7812	CSDE1	GSM4909321	Human	Breast	IDC	2.29e-45	-6.89e-01	0.1559
7812	CSDE1	brca2	Human	Breast	Precancer	1.96e-02	1.02e-01	-0.024
7812	CSDE1	brca3	Human	Breast	Precancer	6.69e-03	2.07e-01	-0.0263
7812	CSDE1	brca10	Human	Breast	Precancer	2.18e-02	-3.68e-01	-0.0029
7812	CSDE1	M2	Human	Breast	IDC	1.14e-07	3.23e-01	0.21

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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
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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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:004670014	Prostate	Tumor	heterocycle catabolic process	117/3246	445/18723	1.11e-06	2.10e-05	117
GO:004427015	Prostate	Tumor	cellular nitrogen compound catabolic process	118/3246	451/18723	1.30e-06	2.39e-05	118
GO:003406313	Prostate	Tumor	stress granule assembly	15/3246	26/18723	4.17e-06	6.64e-05	15
GO:190136114	Prostate	Tumor	organic cyclic compound catabolic process	124/3246	495/18723	7.37e-06	1.10e-04	124
GO:001943914	Prostate	Tumor	aromatic compound catabolic process	118/3246	467/18723	7.92e-06	1.17e-04	118
GO:004666111	Prostate	Tumor	male sex differentiation	48/3246	165/18723	1.25e-04	1.16e-03	48
GO:000840612	Prostate	Tumor	gonad development	60/3246	221/18723	1.68e-04	1.50e-03	60
GO:000858411	Prostate	Tumor	male gonad development	42/3246	141/18723	1.83e-04	1.61e-03	42
GO:004654611	Prostate	Tumor	development of primary male sexual characteristics	42/3246	142/18723	2.17e-04	1.86e-03	42
GO:000754811	Prostate	Tumor	sex differentiation	71/3246	276/18723	2.70e-04	2.24e-03	71
GO:004513712	Prostate	Tumor	development of primary sexual characteristics	60/3246	227/18723	3.65e-04	2.86e-03	60
GO:001603229	Skin	cSCC	viral process	211/4864	415/18723	7.04e-28	2.76e-25	211
GO:000641729	Skin	cSCC	regulation of translation	226/4864	468/18723	8.78e-26	2.62e-23	226
GO:0006413111	Skin	cSCC	translational initiation	84/4864	118/18723	9.12e-25	2.29e-22	84
GO:0006401111	Skin	cSCC	RNA catabolic process	133/4864	278/18723	2.71e-15	2.23e-13	133
GO:000644619	Skin	cSCC	regulation of translational initiation	54/4864	79/18723	3.38e-15	2.72e-13	54
GO:0006402111	Skin	cSCC	mRNA catabolic process	115/4864	232/18723	9.01e-15	6.57e-13	115
GO:0034655111	Skin	cSCC	nucleobase-containing compound catabolic process	172/4864	407/18723	4.11e-13	2.43e-11	172
GO:0046700110	Skin	cSCC	heterocycle catabolic process	178/4864	445/18723	4.45e-11	2.13e-09	178
GO:0044270110	Skin	cSCC	cellular nitrogen compound catabolic process	179/4864	451/18723	8.34e-11	3.79e-09	179

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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

CSDE1

SNV

Missense_Mutation

novel

c.1489N>C

p.Glu497Gln

p.E497Q

O75534

protein_coding

tolerated(0.06)

benign(0.136)

TCGA-AR-A2LE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

CSDE1

SNV

Missense_Mutation

c.772N>T

p.His258Tyr

p.H258Y

O75534

protein_coding

deleterious(0)

probably_damaging(0.922)

TCGA-C8-A12T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CSDE1

SNV

Missense_Mutation

c.114G>C

p.Lys38Asn

p.K38N

O75534

protein_coding

tolerated_low_confidence(0.13)

probably_damaging(0.991)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CSDE1

SNV

Missense_Mutation

c.151N>G

p.Pro51Ala

p.P51A

O75534

protein_coding

tolerated(0.08)

probably_damaging(0.994)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CSDE1

SNV

Missense_Mutation

novel

c.2281G>A

p.Asp761Asn

p.D761N

O75534

protein_coding

deleterious(0.03)

possibly_damaging(0.794)

TCGA-PE-A5DE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

CSDE1

insertion

In_Frame_Ins

novel

c.1798_1799insGATATAGTCCAAAGCAAGGGTTTTATTTAGGCATCTCTAAGC

p.Asp600delinsGlyTyrSerProLysGlnGlyPheTyrLeuGlyIleSerLysHis

p.D600delinsGYSPKQGFYLGISKH

O75534

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

CSDE1

SNV

Missense_Mutation

novel

c.272N>A

p.Arg91His

p.R91H

O75534

protein_coding

deleterious(0)

benign(0.072)

TCGA-PN-A8MA-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CSDE1

SNV

Missense_Mutation

novel

c.95N>T

p.Ser32Phe

p.S32F

O75534

protein_coding

tolerated_low_confidence(0.18)

possibly_damaging(0.663)

TCGA-VS-A8EC-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

carboplatin

CSDE1

SNV

Missense_Mutation

novel

c.2356G>A

p.Glu786Lys

p.E786K

O75534

protein_coding

tolerated(0.09)

benign(0.007)

TCGA-VS-A8EJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CSDE1

SNV

Missense_Mutation

c.681N>T

p.Lys227Asn

p.K227N

O75534

protein_coding

deleterious(0.02)

probably_damaging(0.978)

TCGA-A6-6141-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

5-fu

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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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