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: CEMIP

Gene summary for CEMIP

Gene summary.

Gene information	Species	Human
	Gene symbol	CEMIP
	Gene ID	57214
	Gene name	cell migration inducing hyaluronidase 1
	Gene Alias	CCSP1
	Cytomap	15q25.1
	Gene Type	protein-coding
	GO ID	GO:0001932
	UniProtAcc	Q8WUJ3

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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
57214	CEMIP	A015-C-002	Human	Colorectum	FAP	2.24e-09	7.66e-01	-0.0763
57214	CEMIP	A001-C-203	Human	Colorectum	FAP	2.87e-19	9.25e-01	-0.0481
57214	CEMIP	A002-C-116	Human	Colorectum	FAP	5.82e-05	5.37e-01	-0.0452
57214	CEMIP	A014-C-008	Human	Colorectum	FAP	2.48e-09	7.40e-01	-0.191
57214	CEMIP	A018-E-020	Human	Colorectum	FAP	4.78e-04	4.81e-01	-0.2034
57214	CEMIP	F034	Human	Colorectum	FAP	2.23e-26	9.82e-01	-0.0665
57214	CEMIP	F072B	Human	Colorectum	FAP	3.83e-06	4.35e-01	0.257
57214	CEMIP	CRC-1-8810	Human	Colorectum	CRC	3.66e-24	8.64e-01	0.6257
57214	CEMIP	CRC-3-11773	Human	Colorectum	CRC	3.91e-06	5.24e-01	0.2564
57214	CEMIP	P11T-E	Human	Esophagus	ESCC	2.51e-04	1.29e-01	0.1426
57214	CEMIP	P31T-E	Human	Esophagus	ESCC	2.38e-02	-1.05e-01	0.1251
57214	CEMIP	P48T-E	Human	Esophagus	ESCC	2.27e-05	2.39e-01	0.0959
57214	CEMIP	P54T-E	Human	Esophagus	ESCC	2.70e-14	1.03e+00	0.0975
57214	CEMIP	P62T-E	Human	Esophagus	ESCC	1.11e-09	5.92e-01	0.1302
57214	CEMIP	P65T-E	Human	Esophagus	ESCC	1.41e-05	2.64e-01	0.0978
57214	CEMIP	P79T-E	Human	Esophagus	ESCC	6.59e-06	-3.17e-02	0.1154
57214	CEMIP	P107T-E	Human	Esophagus	ESCC	4.62e-03	4.19e-01	0.171
57214	CEMIP	P130T-E	Human	Esophagus	ESCC	1.39e-24	1.56e+00	0.1676
57214	CEMIP	HCC2_Meng	Human	Liver	HCC	1.95e-12	1.43e-01	0.0107
57214	CEMIP	S014	Human	Liver	HCC	7.44e-07	3.73e-01	0.2254

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma

∗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:190382910	Cervix	CC	positive regulation of cellular protein localization	72/2311	276/18723	3.20e-10	4.46e-08	72
GO:00512359	Cervix	CC	maintenance of location	78/2311	327/18723	5.18e-09	4.92e-07	78
GO:003367410	Cervix	CC	positive regulation of kinase activity	101/2311	467/18723	8.66e-09	7.22e-07	101
GO:005122210	Cervix	CC	positive regulation of protein transport	72/2311	303/18723	2.36e-08	1.70e-06	72
GO:00458608	Cervix	CC	positive regulation of protein kinase activity	85/2311	386/18723	5.61e-08	3.29e-06	85
GO:005165110	Cervix	CC	maintenance of location in cell	55/2311	214/18723	6.63e-08	3.85e-06	55
GO:190495110	Cervix	CC	positive regulation of establishment of protein localization	73/2311	319/18723	9.69e-08	5.25e-06	73
GO:000660510	Cervix	CC	protein targeting	68/2311	314/18723	2.17e-06	6.55e-05	68
GO:00719007	Cervix	CC	regulation of protein serine/threonine kinase activity	75/2311	359/18723	2.76e-06	8.02e-05	75
GO:00903167	Cervix	CC	positive regulation of intracellular protein transport	41/2311	160/18723	3.24e-06	8.80e-05	41
GO:00323868	Cervix	CC	regulation of intracellular transport	71/2311	337/18723	3.70e-06	9.74e-05	71
GO:00331579	Cervix	CC	regulation of intracellular protein transport	52/2311	229/18723	8.16e-06	1.88e-04	52
GO:00719025	Cervix	CC	positive regulation of protein serine/threonine kinase activity	46/2311	200/18723	1.87e-05	3.47e-04	46
GO:19054778	Cervix	CC	positive regulation of protein localization to membrane	29/2311	106/18723	2.29e-05	4.01e-04	29
GO:00323889	Cervix	CC	positive regulation of intracellular transport	46/2311	202/18723	2.45e-05	4.24e-04	46
GO:00901509	Cervix	CC	establishment of protein localization to membrane	54/2311	260/18723	7.67e-05	1.05e-03	54
GO:19054758	Cervix	CC	regulation of protein localization to membrane	36/2311	175/18723	1.33e-03	1.05e-02	36
GO:00181076	Cervix	CC	peptidyl-threonine phosphorylation	25/2311	116/18723	3.59e-03	2.30e-02	25
GO:19035334	Cervix	CC	regulation of protein targeting	19/2311	81/18723	3.96e-03	2.48e-02	19
GO:00182106	Cervix	CC	peptidyl-threonine modification	26/2311	125/18723	4.98e-03	2.97e-02	26

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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

CEMIP

SNV

Missense_Mutation

novel

c.2495A>T

p.Glu832Val

p.E832V

Q8WUJ3

protein_coding

deleterious(0.03)

possibly_damaging(0.617)

TCGA-3C-AALJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

CEMIP

SNV

Missense_Mutation

novel

c.1018G>T

p.Gly340Trp

p.G340W

Q8WUJ3

protein_coding

tolerated(0.39)

benign(0.096)

TCGA-A7-A0DB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

CEMIP

SNV

Missense_Mutation

c.1352N>A

p.Ala451Glu

p.A451E

Q8WUJ3

protein_coding

deleterious(0)

benign(0.422)

TCGA-A8-A08B-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

CEMIP

SNV

Missense_Mutation

c.2273N>T

p.Ser758Leu

p.S758L

Q8WUJ3

protein_coding

deleterious(0.03)

benign(0.086)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CEMIP

SNV

Missense_Mutation

c.2552N>G

p.Asp851Gly

p.D851G

Q8WUJ3

protein_coding

tolerated(0.56)

possibly_damaging(0.73)

TCGA-E2-A1B0-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

CEMIP

deletion

Frame_Shift_Del

rs779771025

c.801delN

p.Pro268LeufsTer5

p.P268Lfs*5

Q8WUJ3

protein_coding

TCGA-A2-A0T5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Taxotere

CEMIP

insertion

Nonsense_Mutation

novel

c.756_757insGATTCTAAGATGCATTATCATAAGAATCATTAACAGGTCAAT

p.Met252_Thr253insAspSerLysMetHisTyrHisLysAsnHisTerGlnValAsn

p.M252_T253insDSKMHYHKNH*QVN

Q8WUJ3

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CEMIP

insertion

Frame_Shift_Ins

novel

c.304_305insCTCCTCTCTTCCATGGGAATGGTCCTGGCAGCCTTCC

p.Asp102AlafsTer40

p.D102Afs*40

Q8WUJ3

protein_coding

TCGA-AN-A0FK-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

CEMIP

insertion

Frame_Shift_Ins

novel

c.2325_2326insTCTACTT

p.Arg776SerfsTer37

p.R776Sfs*37

Q8WUJ3

protein_coding

TCGA-BH-A0EE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

CEMIP

deletion

Frame_Shift_Del

novel

c.3580delN

p.Pro1194ArgfsTer11

p.P1194Rfs*11

Q8WUJ3

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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