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: CYP24A1

Gene summary for CYP24A1

Gene summary.

Gene information	Species	Human
	Gene symbol	CYP24A1
	Gene ID	1591
	Gene name	cytochrome P450 family 24 subfamily A member 1
	Gene Alias	CP24
	Cytomap	20q13.2
	Gene Type	protein-coding
	GO ID	GO:0001503
	UniProtAcc	Q07973

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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
1591	CYP24A1	P2T-E	Human	Esophagus	ESCC	3.89e-03	1.41e-01	0.1177
1591	CYP24A1	P11T-E	Human	Esophagus	ESCC	1.59e-04	1.91e+00	0.1426
1591	CYP24A1	P24T-E	Human	Esophagus	ESCC	1.77e-04	4.97e-01	0.1287
1591	CYP24A1	P36T-E	Human	Esophagus	ESCC	5.15e-03	1.64e+00	0.1187
1591	CYP24A1	P47T-E	Human	Esophagus	ESCC	1.89e-02	-1.65e-02	0.1067
1591	CYP24A1	P48T-E	Human	Esophagus	ESCC	5.37e-08	4.73e-01	0.0959
1591	CYP24A1	P52T-E	Human	Esophagus	ESCC	1.52e-02	4.43e-01	0.1555
1591	CYP24A1	P56T-E	Human	Esophagus	ESCC	8.18e-03	1.28e+00	0.1613
1591	CYP24A1	P62T-E	Human	Esophagus	ESCC	9.63e-40	1.54e+00	0.1302
1591	CYP24A1	P65T-E	Human	Esophagus	ESCC	3.98e-05	3.34e-01	0.0978
1591	CYP24A1	P75T-E	Human	Esophagus	ESCC	1.17e-05	1.03e+00	0.1125
1591	CYP24A1	P107T-E	Human	Esophagus	ESCC	6.56e-04	5.71e-01	0.171
1591	CYP24A1	P130T-E	Human	Esophagus	ESCC	3.73e-10	8.06e-01	0.1676
1591	CYP24A1	C04	Human	Oral cavity	OSCC	4.89e-06	5.28e-01	0.2633
1591	CYP24A1	LN22	Human	Oral cavity	OSCC	6.49e-03	1.20e+00	0.1733
1591	CYP24A1	SYSMH2	Human	Oral cavity	OSCC	2.68e-08	5.53e-01	0.2326
1591	CYP24A1	SYSMH3	Human	Oral cavity	OSCC	3.96e-03	1.72e-01	0.2442
1591	CYP24A1	GSM5252126_BPH283PrGF_Via	Human	Prostate	BPH	1.31e-04	7.28e-01	-0.1771
1591	CYP24A1	GSM5252127_BPH283PrSF_Via	Human	Prostate	BPH	9.93e-10	1.54e+00	-0.1453
1591	CYP24A1	GSM5252133_BPH389PrSF	Human	Prostate	BPH	5.83e-03	7.72e-01	-0.2027

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
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

∗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:0071496111	Esophagus	ESCC	cellular response to external stimulus	215/8552	320/18723	4.29e-15	2.43e-13	215
GO:190136118	Esophagus	ESCC	organic cyclic compound catabolic process	307/8552	495/18723	9.99e-14	4.80e-12	307
GO:0031668111	Esophagus	ESCC	cellular response to extracellular stimulus	168/8552	246/18723	4.93e-13	2.23e-11	168
GO:0031669110	Esophagus	ESCC	cellular response to nutrient levels	148/8552	215/18723	4.58e-12	1.76e-10	148
GO:0031667111	Esophagus	ESCC	response to nutrient levels	289/8552	474/18723	9.25e-12	3.47e-10	289
GO:0030522110	Esophagus	ESCC	intracellular receptor signaling pathway	170/8552	265/18723	8.58e-10	2.09e-08	170
GO:000758410	Esophagus	ESCC	response to nutrient	114/8552	174/18723	9.43e-08	1.56e-06	114
GO:000164918	Esophagus	ESCC	osteoblast differentiation	140/8552	229/18723	1.63e-06	1.95e-05	140
GO:000150317	Esophagus	ESCC	ossification	232/8552	408/18723	3.00e-06	3.40e-05	232
GO:00193958	Esophagus	ESCC	fatty acid oxidation	69/8552	103/18723	9.95e-06	9.44e-05	69
GO:00344407	Esophagus	ESCC	lipid oxidation	71/8552	108/18723	2.00e-05	1.74e-04	71
GO:00066318	Esophagus	ESCC	fatty acid metabolic process	217/8552	390/18723	4.21e-05	3.39e-04	217
GO:00332734	Esophagus	ESCC	response to vitamin	60/8552	93/18723	1.89e-04	1.21e-03	60
GO:00067661	Esophagus	ESCC	vitamin metabolic process	67/8552	106/18723	2.03e-04	1.28e-03	67
GO:00442827	Esophagus	ESCC	small molecule catabolic process	201/8552	376/18723	1.35e-03	6.41e-03	201
GO:0033280	Esophagus	ESCC	response to vitamin D	25/8552	35/18723	1.82e-03	8.35e-03	25
GO:00316701	Esophagus	ESCC	cellular response to nutrient	30/8552	45/18723	3.63e-03	1.48e-02	30
GO:00302586	Esophagus	ESCC	lipid modification	116/8552	212/18723	4.90e-03	1.89e-02	116
GO:00160427	Esophagus	ESCC	lipid catabolic process	168/8552	320/18723	7.97e-03	2.84e-02	168
GO:190136115	Oral cavity	OSCC	organic cyclic compound catabolic process	272/7305	495/18723	2.73e-13	1.36e-11	272

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa001005	Esophagus	ESCC	Steroid biosynthesis	18/4205	20/8465	1.78e-04	6.79e-04	3.48e-04	18
hsa0492816	Esophagus	ESCC	Parathyroid hormone synthesis, secretion and action	66/4205	106/8465	5.86e-03	1.47e-02	7.51e-03	66
hsa0010012	Esophagus	ESCC	Steroid biosynthesis	18/4205	20/8465	1.78e-04	6.79e-04	3.48e-04	18
hsa0492817	Esophagus	ESCC	Parathyroid hormone synthesis, secretion and action	66/4205	106/8465	5.86e-03	1.47e-02	7.51e-03	66
hsa0492814	Prostate	BPH	Parathyroid hormone synthesis, secretion and action	33/1718	106/8465	5.30e-03	1.75e-02	1.08e-02	33
hsa0492815	Prostate	BPH	Parathyroid hormone synthesis, secretion and action	33/1718	106/8465	5.30e-03	1.75e-02	1.08e-02	33
hsa0492822	Prostate	Tumor	Parathyroid hormone synthesis, secretion and action	35/1791	106/8465	2.89e-03	1.07e-02	6.67e-03	35
hsa0492832	Prostate	Tumor	Parathyroid hormone synthesis, secretion and action	35/1791	106/8465	2.89e-03	1.07e-02	6.67e-03	35

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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

CYP24A1

SNV

Missense_Mutation

c.704N>A

p.Ala235Asp

p.A235D

Q07973

protein_coding

deleterious(0.01)

probably_damaging(0.984)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

CYP24A1

SNV

Missense_Mutation

c.1327G>C

p.Glu443Gln

p.E443Q

Q07973

protein_coding

tolerated(0.15)

benign(0.07)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CYP24A1

SNV

Missense_Mutation

c.1247N>C

p.Met416Thr

p.M416T

Q07973

protein_coding

tolerated(1)

benign(0.009)

TCGA-AN-A0FF-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CYP24A1

SNV

Missense_Mutation

c.1195N>C

p.Asp399His

p.D399H

Q07973

protein_coding

deleterious(0.01)

probably_damaging(0.998)

TCGA-EW-A1PC-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

CYP24A1

insertion

Frame_Shift_Ins

novel

c.284_285insAGCCCCTCTCCCGTGCCAT

p.Ile96AlafsTer16

p.I96Afs*16

Q07973

protein_coding

TCGA-A2-A0CM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

CYP24A1

deletion

Frame_Shift_Del

novel

c.465delN

p.Trp155CysfsTer12

p.W155Cfs*12

Q07973

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

CYP24A1

SNV

Missense_Mutation

novel

c.512N>C

p.Glu171Ala

p.E171A

Q07973

protein_coding

tolerated(0.33)

possibly_damaging(0.772)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CYP24A1

SNV

Missense_Mutation

c.1195N>C

p.Asp399His

p.D399H

Q07973

protein_coding

deleterious(0.01)

probably_damaging(0.998)

TCGA-IR-A3LK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

CYP24A1

SNV

Missense_Mutation

c.635T>G

p.Phe212Cys

p.F212C

Q07973

protein_coding

deleterious(0)

probably_damaging(0.991)

TCGA-AA-A00N-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

CYP24A1

SNV

Missense_Mutation

rs116548533

c.1031N>A

p.Arg344His

p.R344H

Q07973

protein_coding

deleterious(0.01)

probably_damaging(0.982)

TCGA-AD-5900-01

Colorectum

colon adenocarcinoma

Male

>=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
1591	CYP24A1	CYTOCHROME P450, DRUGGABLE GENOME, ENZYME		tenofovir disoproxil fumarate		31619748
1591	CYP24A1	CYTOCHROME P450, DRUGGABLE GENOME, ENZYME		deferasirox	DEFERASIROX	29160302,29099735
1591	CYP24A1	CYTOCHROME P450, DRUGGABLE GENOME, ENZYME		CTA018	LUNACALCIPOL
1591	CYP24A1	CYTOCHROME P450, DRUGGABLE GENOME, ENZYME		Lunacalcipol	LUNACALCIPOL
1591	CYP24A1	CYTOCHROME P450, DRUGGABLE GENOME, ENZYME		VITAMIN D		15225763
1591	CYP24A1	CYTOCHROME P450, DRUGGABLE GENOME, ENZYME		CALCITRIOL	CALCITRIOL	25148392
1591	CYP24A1	CYTOCHROME P450, DRUGGABLE GENOME, ENZYME	inhibitor	252827515	CHEMBL255088
1591	CYP24A1	CYTOCHROME P450, DRUGGABLE GENOME, ENZYME	inhibitor	252827476
1591	CYP24A1	CYTOCHROME P450, DRUGGABLE GENOME, ENZYME	inhibitor	252827509
1591	CYP24A1	CYTOCHROME P450, DRUGGABLE GENOME, ENZYME		telaprevir	TELAPREVIR	26158282

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