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:00064138	Breast	Precancer	translational initiation	30/1080	118/18723	3.23e-12	5.58e-10	30
GO:00064179	Breast	Precancer	regulation of translation	67/1080	468/18723	4.71e-12	7.64e-10	67
GO:00160329	Breast	Precancer	viral process	58/1080	415/18723	3.42e-10	3.16e-08	58
GO:00064466	Breast	Precancer	regulation of translational initiation	19/1080	79/18723	7.99e-08	4.60e-06	19
GO:00064028	Breast	Precancer	mRNA catabolic process	31/1080	232/18723	1.12e-05	2.93e-04	31
GO:00064018	Breast	Precancer	RNA catabolic process	34/1080	278/18723	2.88e-05	6.39e-04	34
GO:00346558	Breast	Precancer	nucleobase-containing compound catabolic process	42/1080	407/18723	1.91e-04	3.06e-03	42
GO:00486087	Breast	Precancer	reproductive structure development	43/1080	424/18723	2.36e-04	3.56e-03	43
GO:00614587	Breast	Precancer	reproductive system development	43/1080	427/18723	2.75e-04	4.00e-03	43
GO:00467007	Breast	Precancer	heterocycle catabolic process	44/1080	445/18723	3.49e-04	4.88e-03	44
GO:00442708	Breast	Precancer	cellular nitrogen compound catabolic process	44/1080	451/18723	4.64e-04	6.12e-03	44
GO:00009566	Breast	Precancer	nuclear-transcribed mRNA catabolic process	16/1080	112/18723	6.87e-04	8.36e-03	16
GO:00194397	Breast	Precancer	aromatic compound catabolic process	44/1080	467/18723	9.55e-04	1.07e-02	44
GO:19013617	Breast	Precancer	organic cyclic compound catabolic process	45/1080	495/18723	1.73e-03	1.74e-02	45
GO:00340635	Breast	Precancer	stress granule assembly	6/1080	26/18723	3.09e-03	2.62e-02	6
GO:0046661	Breast	Precancer	male sex differentiation	19/1080	165/18723	3.14e-03	2.65e-02	19
GO:0008584	Breast	Precancer	male gonad development	17/1080	141/18723	3.15e-03	2.65e-02	17
GO:0046546	Breast	Precancer	development of primary male sexual characteristics	17/1080	142/18723	3.39e-03	2.84e-02	17
GO:001603214	Breast	IDC	viral process	75/1434	415/18723	1.98e-12	4.02e-10	75
GO:000641313	Breast	IDC	translational initiation	31/1434	118/18723	7.29e-10	7.52e-08	31

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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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