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: CEP70

Gene summary for CEP70

Gene summary.

Gene information	Species	Human
	Gene symbol	CEP70
	Gene ID	80321
	Gene name	centrosomal protein 70
	Gene Alias	BITE
	Cytomap	3q22.3
	Gene Type	protein-coding
	GO ID	GO:0000226
	UniProtAcc	Q8NHQ1

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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
80321	CEP70	CA_HPV_1	Human	Cervix	CC	8.11e-04	-1.53e-01	0.0264
80321	CEP70	CCI_2	Human	Cervix	CC	3.08e-04	7.02e-01	0.5249
80321	CEP70	CCI_3	Human	Cervix	CC	4.38e-08	6.47e-01	0.516
80321	CEP70	HTA11_3410_2000001011	Human	Colorectum	AD	3.48e-13	-5.30e-01	0.0155
80321	CEP70	HTA11_2487_2000001011	Human	Colorectum	SER	3.74e-07	-5.23e-01	-0.1808
80321	CEP70	HTA11_347_2000001011	Human	Colorectum	AD	5.85e-03	-2.17e-01	-0.1954
80321	CEP70	HTA11_3361_2000001011	Human	Colorectum	AD	2.54e-06	-5.51e-01	-0.1207
80321	CEP70	HTA11_696_2000001011	Human	Colorectum	AD	9.94e-08	-3.96e-01	-0.1464
80321	CEP70	HTA11_866_2000001011	Human	Colorectum	AD	1.22e-11	-4.25e-01	-0.1001
80321	CEP70	HTA11_866_3004761011	Human	Colorectum	AD	2.19e-08	-4.77e-01	0.096
80321	CEP70	HTA11_10711_2000001011	Human	Colorectum	AD	1.13e-02	-3.90e-01	0.0338
80321	CEP70	HTA11_7696_3000711011	Human	Colorectum	AD	2.69e-12	-4.42e-01	0.0674
80321	CEP70	HTA11_6818_2000001021	Human	Colorectum	AD	2.86e-03	-4.94e-01	0.0588
80321	CEP70	HTA11_99999970781_79442	Human	Colorectum	MSS	1.21e-09	-4.30e-01	0.294
80321	CEP70	HTA11_99999971662_82457	Human	Colorectum	MSS	1.82e-15	-5.07e-01	0.3859
80321	CEP70	HTA11_99999973899_84307	Human	Colorectum	MSS	2.77e-08	-6.01e-01	0.2585
80321	CEP70	HTA11_99999974143_84620	Human	Colorectum	MSS	2.18e-22	-5.61e-01	0.3005
80321	CEP70	A001-C-207	Human	Colorectum	FAP	2.65e-02	-2.88e-01	0.1278
80321	CEP70	A015-C-203	Human	Colorectum	FAP	6.93e-18	-3.32e-01	-0.1294
80321	CEP70	A002-C-201	Human	Colorectum	FAP	5.26e-06	-2.28e-01	0.0324

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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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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
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:00705074	Cervix	CC	regulation of microtubule cytoskeleton organization	32/2311	148/18723	1.02e-03	8.51e-03	32
GO:0070507	Colorectum	AD	regulation of microtubule cytoskeleton organization	44/3918	148/18723	7.05e-03	4.31e-02	44
GO:00705071	Colorectum	CRC	regulation of microtubule cytoskeleton organization	30/2078	148/18723	7.75e-04	9.87e-03	30
GO:00705078	Esophagus	ESCC	regulation of microtubule cytoskeleton organization	99/8552	148/18723	1.43e-07	2.29e-06	99
GO:00328864	Esophagus	ESCC	regulation of microtubule-based process	134/8552	240/18723	9.44e-04	4.80e-03	134
GO:00705073	Lung	IAC	regulation of microtubule cytoskeleton organization	29/2061	148/18723	1.44e-03	1.55e-02	29
GO:0060271	Lung	IAC	cilium assembly	55/2061	337/18723	1.84e-03	1.88e-02	55
GO:0044782	Lung	IAC	cilium organization	58/2061	368/18723	3.15e-03	2.75e-02	58
GO:007050712	Lung	AIS	regulation of microtubule cytoskeleton organization	28/1849	148/18723	5.69e-04	8.89e-03	28
GO:00602711	Lung	MIAC	cilium assembly	37/967	337/18723	1.29e-05	9.85e-04	37
GO:00447821	Lung	MIAC	cilium organization	38/967	368/18723	3.93e-05	2.08e-03	38
GO:007050721	Lung	MIAC	regulation of microtubule cytoskeleton organization	18/967	148/18723	6.34e-04	1.55e-02	18
GO:00328861	Lung	MIAC	regulation of microtubule-based process	23/967	240/18723	3.27e-03	4.31e-02	23
GO:00705077	Oral cavity	OSCC	regulation of microtubule cytoskeleton organization	84/7305	148/18723	8.80e-06	9.33e-05	84
GO:00328863	Oral cavity	OSCC	regulation of microtubule-based process	115/7305	240/18723	2.95e-03	1.28e-02	115
GO:00705076	Prostate	BPH	regulation of microtubule cytoskeleton organization	48/3107	148/18723	1.57e-06	2.67e-05	48
GO:00328862	Prostate	BPH	regulation of microtubule-based process	64/3107	240/18723	4.93e-05	5.11e-04	64
GO:007050714	Prostate	Tumor	regulation of microtubule cytoskeleton organization	47/3246	148/18723	1.29e-05	1.78e-04	47
GO:003288611	Prostate	Tumor	regulation of microtubule-based process	65/3246	240/18723	1.00e-04	9.73e-04	65
GO:007050717	Thyroid	PTC	regulation of microtubule cytoskeleton organization	80/5968	148/18723	1.79e-08	4.19e-07	80

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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

CEP70

SNV

Missense_Mutation

novel

c.546N>T

p.Leu182Phe

p.L182F

Q8NHQ1

protein_coding

tolerated(0.18)

benign(0.024)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

CEP70

SNV

Missense_Mutation

c.1717N>G

p.Leu573Val

p.L573V

Q8NHQ1

protein_coding

deleterious(0)

probably_damaging(0.939)

TCGA-A2-A0T0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

CEP70

SNV

Missense_Mutation

c.146G>A

p.Arg49Lys

p.R49K

Q8NHQ1

protein_coding

tolerated(0.83)

benign(0.007)

TCGA-A2-A259-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

CEP70

SNV

Missense_Mutation

novel

c.1436N>A

p.Val479Glu

p.V479E

Q8NHQ1

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-A2-A4S1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CEP70

SNV

Missense_Mutation

rs779132771

c.565N>T

p.Arg189Cys

p.R189C

Q8NHQ1

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CEP70

SNV

Missense_Mutation

c.1644N>G

p.Asp548Glu

p.D548E

Q8NHQ1

protein_coding

deleterious(0)

benign(0.066)

TCGA-AR-A0TZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unspecific

Doxorubicin

CEP70

SNV

Missense_Mutation

c.1199N>A

p.Ala400Glu

p.A400E

Q8NHQ1

protein_coding

deleterious(0)

benign(0.354)

TCGA-BH-A18H-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

CEP70

SNV

Missense_Mutation

novel

c.398C>T

p.Ser133Leu

p.S133L

Q8NHQ1

protein_coding

tolerated(0.11)

probably_damaging(0.996)

TCGA-BH-A2L8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

CEP70

SNV

Missense_Mutation

novel

c.665N>G

p.Ser222Cys

p.S222C

Q8NHQ1

protein_coding

tolerated(0.06)

benign(0.01)

TCGA-PE-A5DE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

CEP70

insertion

Frame_Shift_Ins

novel

c.1127_1128insAACC

p.Gln377ThrfsTer5

p.Q377Tfs*5

Q8NHQ1

protein_coding

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

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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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