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: CLSPN

Gene summary for CLSPN

Gene summary.

Gene information	Species	Human
	Gene symbol	CLSPN
	Gene ID	63967
	Gene name	claspin
	Gene Alias	CLSPN
	Cytomap	1p34.3
	Gene Type	protein-coding
	GO ID	GO:0000075
	UniProtAcc	Q9HAW4

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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
63967	CLSPN	LZE7T	Human	Esophagus	ESCC	6.13e-07	4.59e-01	0.0667
63967	CLSPN	LZE6T	Human	Esophagus	ESCC	5.35e-04	2.02e-01	0.0845
63967	CLSPN	P1T-E	Human	Esophagus	ESCC	4.62e-03	3.11e-01	0.0875
63967	CLSPN	P2T-E	Human	Esophagus	ESCC	2.68e-08	4.30e-01	0.1177
63967	CLSPN	P4T-E	Human	Esophagus	ESCC	6.14e-11	2.89e-01	0.1323
63967	CLSPN	P5T-E	Human	Esophagus	ESCC	1.29e-11	3.60e-01	0.1327
63967	CLSPN	P10T-E	Human	Esophagus	ESCC	1.29e-06	2.62e-01	0.116
63967	CLSPN	P12T-E	Human	Esophagus	ESCC	1.31e-03	1.52e-01	0.1122
63967	CLSPN	P15T-E	Human	Esophagus	ESCC	3.34e-06	2.01e-01	0.1149
63967	CLSPN	P17T-E	Human	Esophagus	ESCC	2.14e-09	3.71e-01	0.1278
63967	CLSPN	P21T-E	Human	Esophagus	ESCC	1.16e-05	3.67e-01	0.1617
63967	CLSPN	P22T-E	Human	Esophagus	ESCC	9.54e-05	1.47e-01	0.1236
63967	CLSPN	P23T-E	Human	Esophagus	ESCC	3.36e-03	1.47e-01	0.108
63967	CLSPN	P24T-E	Human	Esophagus	ESCC	2.89e-04	1.57e-01	0.1287
63967	CLSPN	P26T-E	Human	Esophagus	ESCC	1.48e-03	1.21e-01	0.1276
63967	CLSPN	P27T-E	Human	Esophagus	ESCC	2.04e-06	2.46e-01	0.1055
63967	CLSPN	P28T-E	Human	Esophagus	ESCC	1.29e-12	3.49e-01	0.1149
63967	CLSPN	P30T-E	Human	Esophagus	ESCC	2.13e-03	3.78e-01	0.137
63967	CLSPN	P31T-E	Human	Esophagus	ESCC	1.92e-17	5.34e-01	0.1251
63967	CLSPN	P32T-E	Human	Esophagus	ESCC	7.37e-19	5.02e-01	0.1666

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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
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
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:004477216	Esophagus	ESCC	mitotic cell cycle phase transition	281/8552	424/18723	4.63e-18	4.45e-16	281
GO:000734615	Esophagus	ESCC	regulation of mitotic cell cycle	293/8552	457/18723	8.00e-16	5.64e-14	293
GO:190198713	Esophagus	ESCC	regulation of cell cycle phase transition	242/8552	390/18723	3.86e-11	1.26e-09	242
GO:190199013	Esophagus	ESCC	regulation of mitotic cell cycle phase transition	191/8552	299/18723	1.35e-10	3.94e-09	191
GO:00457865	Esophagus	ESCC	negative regulation of cell cycle	236/8552	385/18723	3.62e-10	9.93e-09	236
GO:00000754	Esophagus	ESCC	cell cycle checkpoint	117/8552	169/18723	4.47e-10	1.17e-08	117
GO:004277014	Esophagus	ESCC	signal transduction in response to DNA damage	117/8552	172/18723	2.38e-09	5.32e-08	117
GO:00448394	Esophagus	ESCC	cell cycle G2/M phase transition	103/8552	148/18723	3.09e-09	6.67e-08	103
GO:00000864	Esophagus	ESCC	G2/M transition of mitotic cell cycle	96/8552	137/18723	6.00e-09	1.23e-07	96
GO:00070934	Esophagus	ESCC	mitotic cell cycle checkpoint	90/8552	129/18723	2.49e-08	4.69e-07	90
GO:00109484	Esophagus	ESCC	negative regulation of cell cycle process	177/8552	294/18723	3.26e-07	4.59e-06	177
GO:00315705	Esophagus	ESCC	DNA integrity checkpoint	83/8552	123/18723	8.17e-07	1.06e-05	83
GO:00000775	Esophagus	ESCC	DNA damage checkpoint	78/8552	115/18723	1.27e-06	1.56e-05	78
GO:19019883	Esophagus	ESCC	negative regulation of cell cycle phase transition	151/8552	249/18723	1.28e-06	1.57e-05	151
GO:004593013	Esophagus	ESCC	negative regulation of mitotic cell cycle	143/8552	235/18723	1.84e-06	2.15e-05	143
GO:00182099	Esophagus	ESCC	peptidyl-serine modification	196/8552	338/18723	3.07e-06	3.47e-05	196
GO:001810515	Esophagus	ESCC	peptidyl-serine phosphorylation	184/8552	315/18723	3.22e-06	3.61e-05	184
GO:190199113	Esophagus	ESCC	negative regulation of mitotic cell cycle phase transition	112/8552	179/18723	3.69e-06	4.03e-05	112
GO:004586018	Esophagus	ESCC	positive regulation of protein kinase activity	219/8552	386/18723	6.91e-06	6.97e-05	219
GO:003367420	Esophagus	ESCC	positive regulation of kinase activity	260/8552	467/18723	7.26e-06	7.22e-05	260

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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

CLSPN

SNV

Missense_Mutation

c.3097G>A

p.Asp1033Asn

p.D1033N

Q9HAW4

protein_coding

deleterious(0.01)

probably_damaging(0.981)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CLSPN

SNV

Missense_Mutation

novel

c.908A>C

p.Asn303Thr

p.N303T

Q9HAW4

protein_coding

tolerated(0.14)

benign(0.337)

TCGA-EW-A1J3-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

CLSPN

SNV

Missense_Mutation

c.1567N>A

p.Glu523Lys

p.E523K

Q9HAW4

protein_coding

tolerated(0.26)

possibly_damaging(0.636)

TCGA-GM-A2D9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

CLSPN

SNV

Missense_Mutation

c.3929N>G

p.Ser1310Cys

p.S1310C

Q9HAW4

protein_coding

deleterious(0.03)

benign(0.428)

TCGA-GM-A2DO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

CLSPN

insertion

In_Frame_Ins

novel

c.2301_2302insTCCGCCCGCCTCGGCCTCCCG

p.Thr767_Lys768insSerAlaArgLeuGlyLeuPro

p.T767_K768insSARLGLP

Q9HAW4

protein_coding

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

CLSPN

insertion

Frame_Shift_Ins

novel

c.2352_2353insAGCTATCATTCCTTGGTGACACATCTTTTCCTTGTTG

p.Gln787HisfsTer50

p.Q787Hfs*50

Q9HAW4

protein_coding

TCGA-A8-A09C-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CLSPN

deletion

Frame_Shift_Del

c.3902delN

p.Lys1301SerfsTer4

p.K1301Sfs*4

Q9HAW4

protein_coding

TCGA-A8-A0AB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

CLSPN

insertion

Nonsense_Mutation

novel

c.2862_2863insTGGTCTTGGTGACACAGGTCA

p.Ser954_Thr955insTrpSerTrpTerHisArgSer

p.S954_T955insWSW*HRS

Q9HAW4

protein_coding

TCGA-AO-A03R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

CLSPN

insertion

Nonsense_Mutation

novel

c.2860_2861insGAGGTCAGGAGTTCAAGACCAG

p.Ser954Ter

p.S954*

Q9HAW4

protein_coding

TCGA-AO-A03R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

CLSPN

insertion

Frame_Shift_Ins

novel

c.3573_3574insTCCACCTGCCTCTGCCTCCCAAAGTGTTGGG

p.Ile1192SerfsTer14

p.I1192Sfs*14

Q9HAW4

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

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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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