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: CENPF

Gene summary for CENPF

Gene summary.

Gene information	Species	Human
	Gene symbol	CENPF
	Gene ID	1063
	Gene name	centromere protein F
	Gene Alias	CENF
	Cytomap	1q41
	Gene Type	protein-coding
	GO ID	GO:0000070
	UniProtAcc	P49454

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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
1063	CENPF	GSM4909281	Human	Breast	IDC	2.14e-05	2.49e-01	0.21
1063	CENPF	GSM4909282	Human	Breast	IDC	1.21e-21	5.87e-01	-0.0288
1063	CENPF	GSM4909285	Human	Breast	IDC	2.22e-05	2.89e-01	0.21
1063	CENPF	GSM4909287	Human	Breast	IDC	3.78e-12	5.19e-01	0.2057
1063	CENPF	GSM4909293	Human	Breast	IDC	2.30e-02	1.47e-01	0.1581
1063	CENPF	GSM4909319	Human	Breast	IDC	7.89e-03	1.62e-01	0.1563
1063	CENPF	M1	Human	Breast	IDC	8.27e-05	3.41e-01	0.1577
1063	CENPF	M2	Human	Breast	IDC	4.85e-08	8.46e-01	0.21
1063	CENPF	NCCBC3	Human	Breast	DCIS	4.65e-06	3.17e-01	0.1198
1063	CENPF	P1	Human	Breast	IDC	4.83e-06	4.35e-01	0.1527
1063	CENPF	P2	Human	Breast	IDC	1.44e-04	4.47e-01	0.21
1063	CENPF	HSIL_HPV_2	Human	Cervix	HSIL_HPV	7.77e-06	3.74e-01	0.0208
1063	CENPF	N_HPV_2	Human	Cervix	N_HPV	7.30e-05	2.44e-01	-0.0131
1063	CENPF	CCI_1	Human	Cervix	CC	1.21e-02	8.25e-01	0.528
1063	CENPF	CCI_2	Human	Cervix	CC	9.23e-22	2.23e+00	0.5249
1063	CENPF	CCI_3	Human	Cervix	CC	8.20e-14	1.93e+00	0.516
1063	CENPF	sample3	Human	Cervix	CC	8.48e-03	1.57e-01	0.1387
1063	CENPF	T1	Human	Cervix	CC	5.86e-03	3.74e-01	0.0918
1063	CENPF	HTA11_696_2000001011	Human	Colorectum	AD	6.21e-05	2.70e-01	-0.1464
1063	CENPF	HTA11_1391_2000001011	Human	Colorectum	AD	2.23e-04	4.21e-01	-0.059

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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
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
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:00070935	Skin	cSCC	mitotic cell cycle checkpoint	54/4864	129/18723	5.99e-05	5.87e-04	54
GO:19021003	Skin	cSCC	negative regulation of metaphase/anaphase transition of cell cycle	23/4864	42/18723	6.79e-05	6.58e-04	23
GO:00519853	Skin	cSCC	negative regulation of chromosome segregation	24/4864	45/18723	8.34e-05	7.94e-04	24
GO:19058193	Skin	cSCC	negative regulation of chromosome separation	24/4864	45/18723	8.34e-05	7.94e-04	24
GO:00513832	Skin	cSCC	kinetochore organization	15/4864	23/18723	8.72e-05	8.21e-04	15
GO:00718241	Skin	cSCC	protein-DNA complex subunit organization	87/4864	241/18723	3.09e-04	2.47e-03	87
GO:0009410110	Skin	cSCC	response to xenobiotic stimulus	151/4864	462/18723	6.76e-04	4.82e-03	151
GO:00345082	Skin	cSCC	centromere complex assembly	16/4864	30/18723	1.27e-03	8.19e-03	16
GO:00513822	Skin	cSCC	kinetochore assembly	11/4864	18/18723	1.74e-03	1.06e-02	11
GO:00103892	Skin	cSCC	regulation of G2/M transition of mitotic cell cycle	37/4864	94/18723	3.02e-03	1.67e-02	37
GO:19027492	Skin	cSCC	regulation of cell cycle G2/M phase transition	38/4864	102/18723	7.85e-03	3.65e-02	38
GO:014001416	Thyroid	ATC	mitotic nuclear division	171/6293	287/18723	1.13e-19	1.66e-17	171
GO:003304423	Thyroid	ATC	regulation of chromosome organization	119/6293	187/18723	3.55e-17	3.40e-15	119
GO:004477219	Thyroid	ATC	mitotic cell cycle phase transition	223/6293	424/18723	3.46e-16	2.88e-14	223
GO:000007013	Thyroid	ATC	mitotic sister chromatid segregation	108/6293	168/18723	3.53e-16	2.90e-14	108
GO:000734622	Thyroid	ATC	regulation of mitotic cell cycle	236/6293	457/18723	7.58e-16	5.92e-14	236
GO:005165625	Thyroid	ATC	establishment of organelle localization	206/6293	390/18723	2.62e-15	1.84e-13	206
GO:000081913	Thyroid	ATC	sister chromatid segregation	122/6293	202/18723	4.71e-15	3.17e-13	122
GO:000705913	Thyroid	ATC	chromosome segregation	183/6293	346/18723	8.03e-14	4.23e-12	183
GO:001063926	Thyroid	ATC	negative regulation of organelle organization	179/6293	348/18723	3.74e-12	1.50e-10	179

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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

CENPF

SNV

Missense_Mutation

novel

c.3773N>C

p.Ile1258Thr

p.I1258T

P49454

protein_coding

tolerated(0.56)

benign(0.007)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

CENPF

SNV

Missense_Mutation

c.2474N>T

p.Ser825Phe

p.S825F

P49454

protein_coding

tolerated(0.41)

benign(0.187)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

CENPF

SNV

Missense_Mutation

novel

c.6094N>G

p.His2032Asp

p.H2032D

P49454

protein_coding

tolerated(0.33)

benign(0.007)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

CENPF

SNV

Missense_Mutation

novel

c.938N>G

p.Asn313Ser

p.N313S

P49454

protein_coding

tolerated(0.09)

benign(0.105)

TCGA-A7-A4SD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

CENPF

SNV

Missense_Mutation

rs555088086

c.1879N>A

p.Glu627Lys

p.E627K

P49454

protein_coding

deleterious(0.05)

possibly_damaging(0.884)

TCGA-A8-A08G-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

CENPF

SNV

Missense_Mutation

novel

c.41N>T

p.Thr14Ile

p.T14I

P49454

protein_coding

deleterious(0.02)

benign(0.281)

TCGA-A8-A09A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

CENPF

SNV

Missense_Mutation

c.830N>T

p.Pro277Leu

p.P277L

P49454

protein_coding

tolerated(0.09)

benign(0.001)

TCGA-A8-A0A7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CENPF

SNV

Missense_Mutation

c.3035C>T

p.Ser1012Leu

p.S1012L

P49454

protein_coding

tolerated(0.12)

benign(0.386)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CENPF

SNV

Missense_Mutation

novel

c.5984A>C

p.Gln1995Pro

p.Q1995P

P49454

protein_coding

deleterious(0.01)

benign(0.317)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CENPF

SNV

Missense_Mutation

novel

c.9248N>A

p.Ser3083Asn

p.S3083N

P49454

protein_coding

tolerated(0.14)

benign(0.297)

TCGA-AN-A0AK-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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