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	CCI_1	Human	Cervix	CC	1.66e-04	5.97e-01	0.528
57214	CEMIP	CCI_2	Human	Cervix	CC	2.71e-03	4.86e-01	0.5249
57214	CEMIP	CCI_3	Human	Cervix	CC	2.81e-03	2.71e-01	0.516
57214	CEMIP	CCII_1	Human	Cervix	CC	2.68e-07	3.29e-01	0.3249
57214	CEMIP	HTA11_3410_2000001011	Human	Colorectum	AD	5.76e-16	6.60e-01	0.0155
57214	CEMIP	HTA11_2951_2000001011	Human	Colorectum	AD	6.57e-04	7.14e-01	0.0216
57214	CEMIP	HTA11_1938_2000001011	Human	Colorectum	AD	2.54e-37	1.66e+00	-0.0811
57214	CEMIP	HTA11_78_2000001011	Human	Colorectum	AD	7.83e-07	8.31e-01	-0.1088
57214	CEMIP	HTA11_696_2000001011	Human	Colorectum	AD	5.31e-03	3.65e-01	-0.1464
57214	CEMIP	HTA11_1391_2000001011	Human	Colorectum	AD	1.13e-24	1.46e+00	-0.059
57214	CEMIP	HTA11_866_3004761011	Human	Colorectum	AD	1.55e-11	6.02e-01	0.096
57214	CEMIP	HTA11_10711_2000001011	Human	Colorectum	AD	1.24e-21	1.49e+00	0.0338
57214	CEMIP	HTA11_7696_3000711011	Human	Colorectum	AD	8.35e-33	1.16e+00	0.0674
57214	CEMIP	HTA11_6818_2000001011	Human	Colorectum	AD	1.44e-03	6.26e-01	0.0112
57214	CEMIP	HTA11_6818_2000001021	Human	Colorectum	AD	1.01e-27	1.34e+00	0.0588
57214	CEMIP	HTA11_99999970781_79442	Human	Colorectum	MSS	2.28e-34	7.97e-01	0.294
57214	CEMIP	HTA11_99999965062_69753	Human	Colorectum	MSI-H	1.08e-06	1.47e+00	0.3487
57214	CEMIP	HTA11_99999965104_69814	Human	Colorectum	MSS	8.79e-10	7.02e-01	0.281
57214	CEMIP	HTA11_99999971662_82457	Human	Colorectum	MSS	1.30e-42	1.24e+00	0.3859
57214	CEMIP	HTA11_99999973899_84307	Human	Colorectum	MSS	4.22e-02	4.32e-01	0.2585

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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:00182101	Colorectum	MSS	peptidyl-threonine modification	36/3467	125/18723	3.28e-03	2.49e-02	36
GO:19038293	Colorectum	MSI-H	positive regulation of cellular protein localization	41/1319	276/18723	4.49e-06	2.37e-04	41
GO:00066053	Colorectum	MSI-H	protein targeting	44/1319	314/18723	9.50e-06	4.55e-04	44
GO:00323863	Colorectum	MSI-H	regulation of intracellular transport	46/1319	337/18723	1.20e-05	5.48e-04	46
GO:19049513	Colorectum	MSI-H	positive regulation of establishment of protein localization	44/1319	319/18723	1.42e-05	6.31e-04	44
GO:00331573	Colorectum	MSI-H	regulation of intracellular protein transport	33/1319	229/18723	6.86e-05	2.29e-03	33
GO:00512223	Colorectum	MSI-H	positive regulation of protein transport	40/1319	303/18723	9.21e-05	2.94e-03	40
GO:00323883	Colorectum	MSI-H	positive regulation of intracellular transport	29/1319	202/18723	1.97e-04	5.30e-03	29
GO:00903163	Colorectum	MSI-H	positive regulation of intracellular protein transport	24/1319	160/18723	3.51e-04	8.20e-03	24
GO:00336743	Colorectum	MSI-H	positive regulation of kinase activity	53/1319	467/18723	3.99e-04	8.98e-03	53
GO:00458603	Colorectum	MSI-H	positive regulation of protein kinase activity	45/1319	386/18723	6.03e-04	1.19e-02	45
GO:00901503	Colorectum	MSI-H	establishment of protein localization to membrane	32/1319	260/18723	1.47e-03	2.23e-02	32
GO:19054753	Colorectum	FAP	regulation of protein localization to membrane	58/2622	175/18723	9.05e-11	2.92e-08	58
GO:19038294	Colorectum	FAP	positive regulation of cellular protein localization	79/2622	276/18723	1.59e-10	4.38e-08	79
GO:19049514	Colorectum	FAP	positive regulation of establishment of protein localization	82/2622	319/18723	1.83e-08	1.87e-06	82
GO:00512224	Colorectum	FAP	positive regulation of protein transport	78/2622	303/18723	3.79e-08	3.23e-06	78
GO:19054773	Colorectum	FAP	positive regulation of protein localization to membrane	37/2622	106/18723	4.79e-08	3.86e-06	37
GO:00901504	Colorectum	FAP	establishment of protein localization to membrane	69/2622	260/18723	6.40e-08	4.54e-06	69
GO:00323884	Colorectum	FAP	positive regulation of intracellular transport	53/2622	202/18723	2.99e-06	1.10e-04	53
GO:00066054	Colorectum	FAP	protein targeting	74/2622	314/18723	3.21e-06	1.17e-04	74

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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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