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: PLK1

Gene summary for PLK1

Gene summary.

Gene information	Species	Human
	Gene symbol	PLK1
	Gene ID	5347
	Gene name	polo like kinase 1
	Gene Alias	PLK
	Cytomap	16p12.2
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P53350

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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
5347	PLK1	LZE2T	Human	Esophagus	ESCC	2.18e-04	8.54e-01	0.082
5347	PLK1	LZE6T	Human	Esophagus	ESCC	3.01e-06	3.67e-01	0.0845
5347	PLK1	P2T-E	Human	Esophagus	ESCC	2.05e-07	6.15e-01	0.1177
5347	PLK1	P4T-E	Human	Esophagus	ESCC	4.27e-09	4.35e-01	0.1323
5347	PLK1	P5T-E	Human	Esophagus	ESCC	3.89e-12	4.96e-01	0.1327
5347	PLK1	P9T-E	Human	Esophagus	ESCC	1.88e-05	3.24e-01	0.1131
5347	PLK1	P17T-E	Human	Esophagus	ESCC	8.50e-05	6.78e-01	0.1278
5347	PLK1	P19T-E	Human	Esophagus	ESCC	7.48e-03	7.89e-01	0.1662
5347	PLK1	P20T-E	Human	Esophagus	ESCC	4.41e-05	4.36e-01	0.1124
5347	PLK1	P21T-E	Human	Esophagus	ESCC	4.12e-11	5.78e-01	0.1617
5347	PLK1	P23T-E	Human	Esophagus	ESCC	9.87e-03	3.02e-01	0.108
5347	PLK1	P24T-E	Human	Esophagus	ESCC	5.30e-21	1.02e+00	0.1287
5347	PLK1	P28T-E	Human	Esophagus	ESCC	4.41e-07	2.29e-01	0.1149
5347	PLK1	P30T-E	Human	Esophagus	ESCC	2.13e-03	4.01e-01	0.137
5347	PLK1	P31T-E	Human	Esophagus	ESCC	2.02e-06	4.34e-01	0.1251
5347	PLK1	P32T-E	Human	Esophagus	ESCC	6.62e-20	8.68e-01	0.1666
5347	PLK1	P36T-E	Human	Esophagus	ESCC	2.11e-03	3.00e-01	0.1187
5347	PLK1	P37T-E	Human	Esophagus	ESCC	1.09e-08	4.31e-01	0.1371
5347	PLK1	P38T-E	Human	Esophagus	ESCC	6.95e-06	3.96e-01	0.127
5347	PLK1	P40T-E	Human	Esophagus	ESCC	6.35e-03	3.78e-01	0.109

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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
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:0010498111	Esophagus	ESCC	proteasomal protein catabolic process	369/8552	490/18723	1.13e-41	1.80e-38	369
GO:0043161111	Esophagus	ESCC	proteasome-mediated ubiquitin-dependent protein catabolic process	312/8552	412/18723	3.53e-36	4.48e-33	312
GO:014001414	Esophagus	ESCC	mitotic nuclear division	218/8552	287/18723	6.17e-26	1.78e-23	218
GO:0042176111	Esophagus	ESCC	regulation of protein catabolic process	280/8552	391/18723	8.65e-26	2.39e-23	280
GO:0031647111	Esophagus	ESCC	regulation of protein stability	223/8552	298/18723	5.76e-25	1.52e-22	223
GO:0022411111	Esophagus	ESCC	cellular component disassembly	305/8552	443/18723	1.94e-23	4.57e-21	305
GO:0009896111	Esophagus	ESCC	positive regulation of catabolic process	332/8552	492/18723	4.36e-23	9.22e-21	332
GO:005165617	Esophagus	ESCC	establishment of organelle localization	273/8552	390/18723	9.13e-23	1.81e-20	273
GO:000007011	Esophagus	ESCC	mitotic sister chromatid segregation	138/8552	168/18723	1.37e-22	2.63e-20	138
GO:0031331111	Esophagus	ESCC	positive regulation of cellular catabolic process	292/8552	427/18723	8.67e-22	1.53e-19	292
GO:003450418	Esophagus	ESCC	protein localization to nucleus	211/8552	290/18723	4.06e-21	6.60e-19	211
GO:00008194	Esophagus	ESCC	sister chromatid segregation	157/8552	202/18723	8.41e-21	1.33e-18	157
GO:1903320111	Esophagus	ESCC	regulation of protein modification by small protein conjugation or removal	181/8552	242/18723	1.80e-20	2.60e-18	181
GO:1903362111	Esophagus	ESCC	regulation of cellular protein catabolic process	188/8552	255/18723	5.12e-20	6.62e-18	188
GO:0051098111	Esophagus	ESCC	regulation of binding	251/8552	363/18723	6.73e-20	8.46e-18	251
GO:0045862111	Esophagus	ESCC	positive regulation of proteolysis	256/8552	372/18723	7.88e-20	9.43e-18	256
GO:1903829111	Esophagus	ESCC	positive regulation of cellular protein localization	199/8552	276/18723	2.99e-19	3.45e-17	199
GO:003304416	Esophagus	ESCC	regulation of chromosome organization	145/8552	187/18723	3.80e-19	4.31e-17	145
GO:000705911	Esophagus	ESCC	chromosome segregation	238/8552	346/18723	1.72e-18	1.82e-16	238
GO:004477216	Esophagus	ESCC	mitotic cell cycle phase transition	281/8552	424/18723	4.63e-18	4.45e-16	281

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0411023	Esophagus	ESCC	Cell cycle	126/4205	157/8465	1.34e-15	5.60e-14	2.87e-14	126
hsa040689	Esophagus	ESCC	FoxO signaling pathway	89/4205	131/8465	1.56e-05	7.98e-05	4.09e-05	89
hsa041146	Esophagus	ESCC	Oocyte meiosis	77/4205	131/8465	2.19e-02	4.80e-02	2.46e-02	77
hsa0411033	Esophagus	ESCC	Cell cycle	126/4205	157/8465	1.34e-15	5.60e-14	2.87e-14	126
hsa0406814	Esophagus	ESCC	FoxO signaling pathway	89/4205	131/8465	1.56e-05	7.98e-05	4.09e-05	89
hsa0411411	Esophagus	ESCC	Oocyte meiosis	77/4205	131/8465	2.19e-02	4.80e-02	2.46e-02	77
hsa041102	Liver	HCC	Cell cycle	106/4020	157/8465	2.54e-07	3.04e-06	1.69e-06	106
hsa040684	Liver	HCC	FoxO signaling pathway	85/4020	131/8465	3.99e-05	2.16e-04	1.20e-04	85
hsa041103	Liver	HCC	Cell cycle	106/4020	157/8465	2.54e-07	3.04e-06	1.69e-06	106
hsa040685	Liver	HCC	FoxO signaling pathway	85/4020	131/8465	3.99e-05	2.16e-04	1.20e-04	85
hsa041108	Oral cavity	OSCC	Cell cycle	118/3704	157/8465	7.15e-16	2.66e-14	1.35e-14	118
hsa040688	Oral cavity	OSCC	FoxO signaling pathway	85/3704	131/8465	7.50e-07	4.33e-06	2.21e-06	85
hsa04114	Oral cavity	OSCC	Oocyte meiosis	74/3704	131/8465	2.13e-03	5.75e-03	2.92e-03	74
hsa0411015	Oral cavity	OSCC	Cell cycle	118/3704	157/8465	7.15e-16	2.66e-14	1.35e-14	118
hsa0406813	Oral cavity	OSCC	FoxO signaling pathway	85/3704	131/8465	7.50e-07	4.33e-06	2.21e-06	85
hsa041141	Oral cavity	OSCC	Oocyte meiosis	74/3704	131/8465	2.13e-03	5.75e-03	2.92e-03	74

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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

PLK1

SNV

Missense_Mutation

c.732G>C

p.Leu244Phe

p.L244F

P53350

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A8-A094-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PLK1

SNV

Missense_Mutation

c.658C>G

p.Pro220Ala

p.P220A

P53350

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-A8-A09G-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

PLK1

SNV

Missense_Mutation

novel

c.1729G>C

p.Ala577Pro

p.A577P

P53350

protein_coding

tolerated(0.19)

probably_damaging(0.937)

TCGA-AR-A1AP-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

PLK1

insertion

Frame_Shift_Ins

novel

c.751_752insCATACGTCTTTGCAGTGGGGTTTTTTCAAATGAAAAC

p.Phe251SerfsTer14

p.F251Sfs*14

P53350

protein_coding

TCGA-A2-A0CU-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

PLK1

insertion

Nonsense_Mutation

novel

c.1150_1151insCAGTGGCGCGCAGGCTTTTGTAACGT

p.Val384AlafsTer8

p.V384Afs*8

P53350

protein_coding

TCGA-A8-A0A6-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

epirubicin

PLK1

insertion

In_Frame_Ins

novel

c.694_695insACAGCATTTTCTTAGGGCAGCCCTTTGCTGGGC

p.Val232delinsAspSerIlePheLeuGlyGlnProPheAlaGlyLeu

p.V232delinsDSIFLGQPFAGL

P53350

protein_coding

TCGA-AN-A03Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PLK1

deletion

Frame_Shift_Del

novel

c.403delC

p.Arg135GlyfsTer14

p.R135Gfs*14

P53350

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

PLK1

SNV

Missense_Mutation

rs749527952

c.977N>T

p.Ser326Leu

p.S326L

P53350

protein_coding

tolerated(0.07)

benign(0.117)

TCGA-EA-A50E-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

PLK1

SNV

Missense_Mutation

c.1736G>A

p.Arg579Gln

p.R579Q

P53350

protein_coding

deleterious(0.01)

probably_damaging(0.994)

TCGA-5M-AAT6-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Unknown

PLK1

SNV

Missense_Mutation

c.596C>T

p.Thr199Ile

p.T199I

P53350

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A6-6780-01

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
5347	PLK1	TRANSCRIPTION FACTOR, KINASE, TUMOR SUPPRESSOR, SERINE THREONINE KINASE, ENZYME, DRUGGABLE GENOME		DNDI1417055	CHEMBL1486366
5347	PLK1	TRANSCRIPTION FACTOR, KINASE, TUMOR SUPPRESSOR, SERINE THREONINE KINASE, ENZYME, DRUGGABLE GENOME		NSC-7387	CHEMBL119878
5347	PLK1	TRANSCRIPTION FACTOR, KINASE, TUMOR SUPPRESSOR, SERINE THREONINE KINASE, ENZYME, DRUGGABLE GENOME		DNDI1417601	CHEMBL1503729
5347	PLK1	TRANSCRIPTION FACTOR, KINASE, TUMOR SUPPRESSOR, SERINE THREONINE KINASE, ENZYME, DRUGGABLE GENOME		PLK-1 INHIBITOR
5347	PLK1	TRANSCRIPTION FACTOR, KINASE, TUMOR SUPPRESSOR, SERINE THREONINE KINASE, ENZYME, DRUGGABLE GENOME		LANSOPRAZOLE	LANSOPRAZOLE
5347	PLK1	TRANSCRIPTION FACTOR, KINASE, TUMOR SUPPRESSOR, SERINE THREONINE KINASE, ENZYME, DRUGGABLE GENOME		2-ANILINOPYRIDINE	CHEMBL555260
5347	PLK1	TRANSCRIPTION FACTOR, KINASE, TUMOR SUPPRESSOR, SERINE THREONINE KINASE, ENZYME, DRUGGABLE GENOME		SOTRASTAURIN	SOTRASTAURIN
5347	PLK1	TRANSCRIPTION FACTOR, KINASE, TUMOR SUPPRESSOR, SERINE THREONINE KINASE, ENZYME, DRUGGABLE GENOME		DNDI1417400	CHEMBL1362503
5347	PLK1	TRANSCRIPTION FACTOR, KINASE, TUMOR SUPPRESSOR, SERINE THREONINE KINASE, ENZYME, DRUGGABLE GENOME		PRODINE HYDROCHLORIDE	ALPHAPRODINE HYDROCHLORIDE
5347	PLK1	TRANSCRIPTION FACTOR, KINASE, TUMOR SUPPRESSOR, SERINE THREONINE KINASE, ENZYME, DRUGGABLE GENOME		GW843682X	GW843682X

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