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: FOXK1

Gene summary for FOXK1

Gene summary.

Gene information	Species	Human
	Gene symbol	FOXK1
	Gene ID	221937
	Gene name	forkhead box K1
	Gene Alias	FOXK1L
	Cytomap	7p22.1
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	P85037

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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
221937	FOXK1	CCI_1	Human	Cervix	CC	7.80e-15	9.32e-01	0.528
221937	FOXK1	CCI_2	Human	Cervix	CC	2.38e-14	1.21e+00	0.5249
221937	FOXK1	CCI_3	Human	Cervix	CC	4.97e-19	1.04e+00	0.516
221937	FOXK1	LZE7T	Human	Esophagus	ESCC	8.27e-05	2.23e-01	0.0667
221937	FOXK1	LZE24T	Human	Esophagus	ESCC	8.17e-04	4.31e-02	0.0596
221937	FOXK1	P1T-E	Human	Esophagus	ESCC	6.56e-05	1.68e-01	0.0875
221937	FOXK1	P2T-E	Human	Esophagus	ESCC	2.44e-15	3.86e-02	0.1177
221937	FOXK1	P4T-E	Human	Esophagus	ESCC	4.51e-08	7.52e-02	0.1323
221937	FOXK1	P5T-E	Human	Esophagus	ESCC	8.03e-12	4.74e-02	0.1327
221937	FOXK1	P8T-E	Human	Esophagus	ESCC	1.31e-14	1.00e-01	0.0889
221937	FOXK1	P9T-E	Human	Esophagus	ESCC	3.30e-11	1.87e-01	0.1131
221937	FOXK1	P10T-E	Human	Esophagus	ESCC	2.31e-20	4.80e-01	0.116
221937	FOXK1	P11T-E	Human	Esophagus	ESCC	4.26e-02	6.49e-02	0.1426
221937	FOXK1	P12T-E	Human	Esophagus	ESCC	1.21e-13	1.54e-02	0.1122
221937	FOXK1	P15T-E	Human	Esophagus	ESCC	2.94e-12	1.77e-01	0.1149
221937	FOXK1	P16T-E	Human	Esophagus	ESCC	6.24e-12	4.94e-02	0.1153
221937	FOXK1	P17T-E	Human	Esophagus	ESCC	5.05e-09	2.02e-01	0.1278
221937	FOXK1	P20T-E	Human	Esophagus	ESCC	3.28e-02	-3.29e-02	0.1124
221937	FOXK1	P21T-E	Human	Esophagus	ESCC	7.19e-06	4.56e-02	0.1617
221937	FOXK1	P22T-E	Human	Esophagus	ESCC	6.41e-06	-1.26e-02	0.1236

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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
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
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:004603410	Cervix	CC	ATP metabolic process	90/2311	277/18723	7.90e-19	2.36e-15	90
GO:00060919	Cervix	CC	generation of precursor metabolites and energy	105/2311	490/18723	7.40e-09	6.61e-07	105
GO:003133010	Cervix	CC	negative regulation of cellular catabolic process	63/2311	262/18723	1.10e-07	5.68e-06	63
GO:000989510	Cervix	CC	negative regulation of catabolic process	69/2311	320/18723	2.15e-06	6.55e-05	69
GO:003166710	Cervix	CC	response to nutrient levels	92/2311	474/18723	5.80e-06	1.42e-04	92
GO:00425948	Cervix	CC	response to starvation	46/2311	197/18723	1.24e-05	2.59e-04	46
GO:00105067	Cervix	CC	regulation of autophagy	61/2311	317/18723	2.61e-04	2.87e-03	61
GO:00196939	Cervix	CC	ribose phosphate metabolic process	72/2311	396/18723	4.49e-04	4.48e-03	72
GO:00092599	Cervix	CC	ribonucleotide metabolic process	70/2311	385/18723	5.35e-04	5.18e-03	70
GO:00425939	Cervix	CC	glucose homeostasis	50/2311	258/18723	7.57e-04	6.76e-03	50
GO:00335009	Cervix	CC	carbohydrate homeostasis	50/2311	259/18723	8.28e-04	7.22e-03	50
GO:00016788	Cervix	CC	cellular glucose homeostasis	36/2311	172/18723	9.65e-04	8.09e-03	36
GO:000915010	Cervix	CC	purine ribonucleotide metabolic process	66/2311	368/18723	1.09e-03	9.07e-03	66
GO:00075173	Cervix	CC	muscle organ development	58/2311	327/18723	2.73e-03	1.85e-02	58
GO:000616310	Cervix	CC	purine nucleotide metabolic process	67/2311	396/18723	4.41e-03	2.69e-02	67
GO:007252110	Cervix	CC	purine-containing compound metabolic process	69/2311	416/18723	6.27e-03	3.54e-02	69
GO:00067346	Cervix	CC	NADH metabolic process	9/2311	29/18723	6.49e-03	3.61e-02	9
GO:000913510	Cervix	CC	purine nucleoside diphosphate metabolic process	22/2311	103/18723	6.75e-03	3.71e-02	22
GO:000917910	Cervix	CC	purine ribonucleoside diphosphate metabolic process	22/2311	103/18723	6.75e-03	3.71e-02	22
GO:000911710	Cervix	CC	nucleotide metabolic process	79/2311	489/18723	7.16e-03	3.85e-02	79

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
FOXK1	CD8TEFF	Breast	DCIS	MFSD8,NDC80,HIST1H2AL, etc.	1.21e-01
FOXK1	GC	Colorectum	AD	SGPP2,SLC12A2,PHPT1, etc.	3.52e-02
FOXK1	TFH	Colorectum	AD	SGPP2,SLC12A2,PHPT1, etc.	2.22e-16
FOXK1	BN	Colorectum	AD	SGPP2,SLC12A2,PHPT1, etc.	2.22e-16
FOXK1	CD8TEREX	Colorectum	CRC	SGPP2,SLC12A2,PHPT1, etc.	5.25e-02
FOXK1	ILC	Colorectum	CRC	SGPP2,SLC12A2,PHPT1, etc.	2.92e-02
FOXK1	CD8TEXINT	Colorectum	FAP	SGPP2,SLC12A2,PHPT1, etc.	2.34e-02
FOXK1	BN	Colorectum	Healthy	SGPP2,SLC12A2,PHPT1, etc.	2.31e-02
FOXK1	CD8TCM	Colorectum	Healthy	SGPP2,SLC12A2,PHPT1, etc.	3.39e-02
FOXK1	CD8TEREX	Colorectum	MSI-H	SGPP2,SLC12A2,PHPT1, etc.	1.71e-01

∗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

FOXK1

SNV

Missense_Mutation

rs750121455

c.2047N>C

p.Thr683Pro

p.T683P

P85037

protein_coding

tolerated_low_confidence(0.13)

benign(0.137)

TCGA-A7-A3IY-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

FOXK1

SNV

Missense_Mutation

rs750121455

c.2047N>C

p.Thr683Pro

p.T683P

P85037

protein_coding

tolerated_low_confidence(0.13)

benign(0.137)

TCGA-AR-A1AM-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

FOXK1

SNV

Missense_Mutation

c.689N>T

p.Pro230Leu

p.P230L

P85037

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AR-A1AT-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

anastrozole

FOXK1

SNV

Missense_Mutation

c.1189C>T

p.Arg397Trp

p.R397W

P85037

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-OL-A5DA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

FOXK1

insertion

Nonsense_Mutation

novel

c.992_993insTTCTGGAAGAGGTGAGAAATTTCAGAATTAAATTATAATAAAAC

p.Tyr332SerfsTer10

p.Y332Sfs*10

P85037

protein_coding

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

FOXK1

SNV

Missense_Mutation

novel

c.1546G>A

p.Val516Met

p.V516M

P85037

protein_coding

deleterious(0)

possibly_damaging(0.849)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

FOXK1

SNV

Missense_Mutation

novel

c.622G>A

p.Glu208Lys

p.E208K

P85037

protein_coding

tolerated(0.19)

benign(0.027)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

FOXK1

SNV

Missense_Mutation

novel

c.518N>T

p.Ala173Val

p.A173V

P85037

protein_coding

tolerated(1)

benign(0.003)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

FOXK1

SNV

Missense_Mutation

c.2011N>A

p.Glu671Lys

p.E671K

P85037

protein_coding

deleterious_low_confidence(0.02)

benign(0.012)

TCGA-EK-A2RK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

FOXK1

SNV

Missense_Mutation

novel

c.1081N>T

p.Arg361Cys

p.R361C

P85037

protein_coding

deleterious(0.03)

probably_damaging(0.999)

TCGA-VS-A8QC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

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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