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: CDKN1A

Gene summary for CDKN1A

Gene summary.

Gene information	Species	Human
	Gene symbol	CDKN1A
	Gene ID	1026
	Gene name	cyclin dependent kinase inhibitor 1A
	Gene Alias	CAP20
	Cytomap	6p21.2
	Gene Type	protein-coding
	GO ID	GO:0000075
	UniProtAcc	A0A024RCX5

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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
1026	CDKN1A	Tumor	Human	Cervix	CC	2.30e-10	4.03e-01	0.1241
1026	CDKN1A	sample1	Human	Cervix	CC	3.15e-11	6.48e-01	0.0959
1026	CDKN1A	sample3	Human	Cervix	CC	1.27e-26	5.83e-01	0.1387
1026	CDKN1A	L1	Human	Cervix	CC	4.84e-06	3.03e-01	0.0802
1026	CDKN1A	T1	Human	Cervix	CC	1.31e-17	6.07e-01	0.0918
1026	CDKN1A	T2	Human	Cervix	CC	6.30e-06	6.12e-01	0.0709
1026	CDKN1A	T3	Human	Cervix	CC	3.85e-16	5.18e-01	0.1389
1026	CDKN1A	HTA11_3410_2000001011	Human	Colorectum	AD	5.62e-08	2.88e-01	0.0155
1026	CDKN1A	HTA11_2487_2000001011	Human	Colorectum	SER	2.29e-43	1.70e+00	-0.1808
1026	CDKN1A	HTA11_2951_2000001011	Human	Colorectum	AD	1.08e-02	5.09e-01	0.0216
1026	CDKN1A	HTA11_1938_2000001011	Human	Colorectum	AD	2.10e-21	1.09e+00	-0.0811
1026	CDKN1A	HTA11_78_2000001011	Human	Colorectum	AD	2.79e-26	8.86e-01	-0.1088
1026	CDKN1A	HTA11_347_2000001011	Human	Colorectum	AD	2.15e-24	7.79e-01	-0.1954
1026	CDKN1A	HTA11_411_2000001011	Human	Colorectum	SER	5.70e-16	2.45e+00	-0.2602
1026	CDKN1A	HTA11_2112_2000001011	Human	Colorectum	SER	3.75e-18	2.12e+00	-0.2196
1026	CDKN1A	HTA11_3361_2000001011	Human	Colorectum	AD	6.88e-28	1.11e+00	-0.1207
1026	CDKN1A	HTA11_83_2000001011	Human	Colorectum	SER	5.14e-11	7.49e-01	-0.1526
1026	CDKN1A	HTA11_696_2000001011	Human	Colorectum	AD	1.05e-30	1.24e+00	-0.1464
1026	CDKN1A	HTA11_866_2000001011	Human	Colorectum	AD	1.29e-08	4.67e-01	-0.1001
1026	CDKN1A	HTA11_1391_2000001011	Human	Colorectum	AD	2.59e-38	1.57e+00	-0.059

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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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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
Prostate		BPH: Benign Prostatic Hyperplasia
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:005138421	Liver	HCC	response to glucocorticoid	90/7958	148/18723	5.18e-06	6.47e-05	90
GO:000926712	Liver	HCC	cellular response to starvation	94/7958	156/18723	5.61e-06	6.95e-05	94
GO:00000751	Liver	HCC	cell cycle checkpoint	100/7958	169/18723	8.75e-06	1.02e-04	100
GO:001021221	Liver	HCC	response to ionizing radiation	89/7958	148/18723	1.10e-05	1.26e-04	89
GO:007233212	Liver	HCC	intrinsic apoptotic signaling pathway by p53 class mediator	51/7958	76/18723	1.27e-05	1.42e-04	51
GO:003196021	Liver	HCC	response to corticosteroid	98/7958	167/18723	1.73e-05	1.87e-04	98
GO:0045786	Liver	HCC	negative regulation of cell cycle	204/7958	385/18723	1.84e-05	1.99e-04	204
GO:00448432	Liver	HCC	cell cycle G1/S phase transition	134/7958	241/18723	2.60e-05	2.70e-04	134
GO:200037722	Liver	HCC	regulation of reactive oxygen species metabolic process	92/7958	157/18723	3.34e-05	3.35e-04	92
GO:005110012	Liver	HCC	negative regulation of binding	94/7958	162/18723	4.69e-05	4.50e-04	94
GO:0045930	Liver	HCC	negative regulation of mitotic cell cycle	130/7958	235/18723	4.69e-05	4.50e-04	130
GO:004206022	Liver	HCC	wound healing	219/7958	422/18723	5.34e-05	5.04e-04	219
GO:003209112	Liver	HCC	negative regulation of protein binding	59/7958	94/18723	5.79e-05	5.34e-04	59
GO:007190021	Liver	HCC	regulation of protein serine/threonine kinase activity	189/7958	359/18723	5.97e-05	5.47e-04	189
GO:0007093	Liver	HCC	mitotic cell cycle checkpoint	77/7958	129/18723	6.00e-05	5.50e-04	77
GO:009730522	Liver	HCC	response to alcohol	138/7958	253/18723	6.91e-05	6.26e-04	138
GO:00000822	Liver	HCC	G1/S transition of mitotic cell cycle	119/7958	214/18723	7.11e-05	6.39e-04	119
GO:007147921	Liver	HCC	cellular response to ionizing radiation	47/7958	72/18723	7.95e-05	7.07e-04	47
GO:000926611	Liver	HCC	response to temperature stimulus	101/7958	178/18723	8.55e-05	7.48e-04	101
GO:00346441	Liver	HCC	cellular response to UV	56/7958	90/18723	1.25e-04	1.03e-03	56

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0516720	Cervix	CC	Kaposi sarcoma-associated herpesvirus infection	60/1267	194/8465	9.74e-09	1.58e-07	9.33e-08	60
hsa0516318	Cervix	CC	Human cytomegalovirus infection	65/1267	225/8465	4.59e-08	6.47e-07	3.83e-07	65
hsa0520516	Cervix	CC	Proteoglycans in cancer	60/1267	205/8465	9.13e-08	1.18e-06	7.00e-07	60
hsa0421810	Cervix	CC	Cellular senescence	49/1267	156/8465	1.30e-07	1.63e-06	9.61e-07	49
hsa0516920	Cervix	CC	Epstein-Barr virus infection	57/1267	202/8465	7.30e-07	7.39e-06	4.37e-06	57
hsa0516620	Cervix	CC	Human T-cell leukemia virus 1 infection	61/1267	222/8465	8.13e-07	7.98e-06	4.72e-06	61
hsa0401210	Cervix	CC	ErbB signaling pathway	28/1267	85/8465	2.40e-05	1.82e-04	1.08e-04	28
hsa052197	Cervix	CC	Bladder cancer	16/1267	41/8465	1.45e-04	9.05e-04	5.35e-04	16
hsa051657	Cervix	CC	Human papillomavirus infection	74/1267	331/8465	1.70e-04	1.02e-03	6.03e-04	74
hsa015223	Cervix	CC	Endocrine resistance	28/1267	98/8465	3.82e-04	1.87e-03	1.11e-03	28
hsa0492812	Cervix	CC	Parathyroid hormone synthesis, secretion and action	27/1267	106/8465	3.12e-03	1.19e-02	7.03e-03	27
hsa0406618	Cervix	CC	HIF-1 signaling pathway	27/1267	109/8465	4.72e-03	1.64e-02	9.72e-03	27
hsa041106	Cervix	CC	Cell cycle	36/1267	157/8465	4.94e-03	1.67e-02	9.86e-03	36
hsa05167110	Cervix	CC	Kaposi sarcoma-associated herpesvirus infection	60/1267	194/8465	9.74e-09	1.58e-07	9.33e-08	60
hsa0516319	Cervix	CC	Human cytomegalovirus infection	65/1267	225/8465	4.59e-08	6.47e-07	3.83e-07	65
hsa0520517	Cervix	CC	Proteoglycans in cancer	60/1267	205/8465	9.13e-08	1.18e-06	7.00e-07	60
hsa0421815	Cervix	CC	Cellular senescence	49/1267	156/8465	1.30e-07	1.63e-06	9.61e-07	49
hsa05169110	Cervix	CC	Epstein-Barr virus infection	57/1267	202/8465	7.30e-07	7.39e-06	4.37e-06	57
hsa05166110	Cervix	CC	Human T-cell leukemia virus 1 infection	61/1267	222/8465	8.13e-07	7.98e-06	4.72e-06	61
hsa0401213	Cervix	CC	ErbB signaling pathway	28/1267	85/8465	2.40e-05	1.82e-04	1.08e-04	28

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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

CDKN1A

SNV

Missense_Mutation

novel

c.458C>G

p.Ser153Cys

p.S153C

P38936

protein_coding

deleterious(0)

probably_damaging(0.956)

TCGA-C5-A8YR-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

CDKN1A

SNV

Missense_Mutation

rs779717089

c.256N>T

p.Arg86Trp

p.R86W

P38936

protein_coding

tolerated(0.22)

benign(0.005)

TCGA-DS-A1OA-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

carboplatin

CDKN1A

SNV

Missense_Mutation

novel

c.280C>T

p.Arg94Trp

p.R94W

P38936

protein_coding

tolerated(0.11)

benign(0.005)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

CDKN1A

deletion

Frame_Shift_Del

novel

c.250_268delCGAGGCCGGGATGAGTTGG

p.Arg84GlufsTer58

p.R84Efs*58

P38936

protein_coding

TCGA-ZJ-A8QR-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

CDKN1A

SNV

Missense_Mutation

rs376481017

c.97N>A

p.Asp33Asn

p.D33N

P38936

protein_coding

deleterious(0.01)

probably_damaging(0.994)

TCGA-AA-3492-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

CDKN1A

SNV

Missense_Mutation

rs753291170

c.166G>A

p.Glu56Lys

p.E56K

P38936

protein_coding

deleterious(0)

probably_damaging(0.926)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

CDKN1A

SNV

Missense_Mutation

c.115N>A

p.Ala39Thr

p.A39T

P38936

protein_coding

tolerated(0.15)

benign(0.419)

TCGA-A5-A2K7-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

taxol

CDKN1A

SNV

Missense_Mutation

rs774390644

c.424N>T

p.Arg142Trp

p.R142W

P38936

protein_coding

deleterious(0)

probably_damaging(0.913)

TCGA-AJ-A3BH-01

Endometrium

uterine corpus endometrioid carcinoma

Female

Unknown

I/II

Unknown

CDKN1A

SNV

Missense_Mutation

rs372390764

c.199C>T

p.Arg67Cys

p.R67C

P38936

protein_coding

deleterious(0.04)

probably_damaging(0.927)

TCGA-AJ-A8CT-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CDKN1A

SNV

Missense_Mutation

rs748758330

c.205N>T

p.Arg69Trp

p.R69W

P38936

protein_coding

tolerated(0.23)

benign(0.005)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid 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
1026	CDKN1A	CLINICALLY ACTIONABLE, DRUG RESISTANCE, KINASE, TUMOR SUPPRESSOR, DRUGGABLE GENOME		ANTIMETABOLITE		10997587
1026	CDKN1A	CLINICALLY ACTIONABLE, DRUG RESISTANCE, KINASE, TUMOR SUPPRESSOR, DRUGGABLE GENOME		celecoxib	CELECOXIB	22336956
1026	CDKN1A	CLINICALLY ACTIONABLE, DRUG RESISTANCE, KINASE, TUMOR SUPPRESSOR, DRUGGABLE GENOME		SODIUM PHENYLBUTYRATE		16246228
1026	CDKN1A	CLINICALLY ACTIONABLE, DRUG RESISTANCE, KINASE, TUMOR SUPPRESSOR, DRUGGABLE GENOME		MAPK INHIBITORS		16170570
1026	CDKN1A	CLINICALLY ACTIONABLE, DRUG RESISTANCE, KINASE, TUMOR SUPPRESSOR, DRUGGABLE GENOME		L-PAM	MELPHALAN	11507071
1026	CDKN1A	CLINICALLY ACTIONABLE, DRUG RESISTANCE, KINASE, TUMOR SUPPRESSOR, DRUGGABLE GENOME		ACNU		9537648
1026	CDKN1A	CLINICALLY ACTIONABLE, DRUG RESISTANCE, KINASE, TUMOR SUPPRESSOR, DRUGGABLE GENOME		PACLITAXEL	PACLITAXEL	12574211
1026	CDKN1A	CLINICALLY ACTIONABLE, DRUG RESISTANCE, KINASE, TUMOR SUPPRESSOR, DRUGGABLE GENOME		NICOTINE	NICOTINE	16011614
1026	CDKN1A	CLINICALLY ACTIONABLE, DRUG RESISTANCE, KINASE, TUMOR SUPPRESSOR, DRUGGABLE GENOME		CARBOPLATIN	CARBOPLATIN	12168940
1026	CDKN1A	CLINICALLY ACTIONABLE, DRUG RESISTANCE, KINASE, TUMOR SUPPRESSOR, DRUGGABLE GENOME		PTHRP		11136536

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