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: KLF5

Gene summary for KLF5

Gene summary.

Gene information	Species	Human
	Gene symbol	KLF5
	Gene ID	688
	Gene name	Kruppel like factor 5
	Gene Alias	BTEB2
	Cytomap	13q22.1
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	Q13887

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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
688	KLF5	CA_HPV_1	Human	Cervix	CC	1.72e-10	-3.73e-01	0.0264
688	KLF5	CA_HPV_3	Human	Cervix	CC	5.22e-04	1.83e-01	0.0414
688	KLF5	HSIL_HPV_1	Human	Cervix	HSIL_HPV	5.93e-04	-3.29e-01	0.0116
688	KLF5	CCI_1	Human	Cervix	CC	1.75e-09	1.35e+00	0.528
688	KLF5	CCI_2	Human	Cervix	CC	3.11e-02	6.41e-01	0.5249
688	KLF5	CCI_3	Human	Cervix	CC	8.15e-03	6.79e-01	0.516
688	KLF5	Tumor	Human	Cervix	CC	1.83e-30	7.09e-01	0.1241
688	KLF5	sample3	Human	Cervix	CC	5.93e-58	8.55e-01	0.1387
688	KLF5	H2	Human	Cervix	HSIL_HPV	5.86e-11	4.51e-01	0.0632
688	KLF5	L1	Human	Cervix	CC	1.49e-03	3.89e-01	0.0802
688	KLF5	T1	Human	Cervix	CC	3.46e-07	4.21e-01	0.0918
688	KLF5	T2	Human	Cervix	CC	1.77e-04	5.97e-01	0.0709
688	KLF5	T3	Human	Cervix	CC	1.18e-50	8.52e-01	0.1389
688	KLF5	HTA11_3410_2000001011	Human	Colorectum	AD	7.10e-11	-4.06e-01	0.0155
688	KLF5	HTA11_347_2000001011	Human	Colorectum	AD	1.67e-40	1.35e+00	-0.1954
688	KLF5	HTA11_411_2000001011	Human	Colorectum	SER	6.74e-12	9.87e-01	-0.2602
688	KLF5	HTA11_696_2000001011	Human	Colorectum	AD	2.96e-05	4.61e-01	-0.1464
688	KLF5	HTA11_866_2000001011	Human	Colorectum	AD	5.38e-03	3.89e-01	-0.1001
688	KLF5	HTA11_546_2000001011	Human	Colorectum	AD	2.88e-05	5.82e-01	-0.0842
688	KLF5	HTA11_9408_2000001011	Human	Colorectum	AD	1.25e-02	-5.32e-01	0.0451

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
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
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:190289312	Liver	HCC	regulation of pri-miRNA transcription by RNA polymerase II	34/7958	54/18723	1.92e-03	9.78e-03	34
GO:000206422	Liver	HCC	epithelial cell development	114/7958	220/18723	3.19e-03	1.47e-02	114
GO:00020648	Lung	IAC	epithelial cell development	52/2061	220/18723	6.75e-08	6.91e-06	52
GO:19016537	Lung	IAC	cellular response to peptide	69/2061	359/18723	2.62e-06	1.14e-04	69
GO:00616147	Lung	IAC	pri-miRNA transcription by RNA polymerase II	19/2061	55/18723	3.20e-06	1.38e-04	19
GO:19028937	Lung	IAC	regulation of pri-miRNA transcription by RNA polymerase II	18/2061	54/18723	1.02e-05	3.23e-04	18
GO:19028954	Lung	IAC	positive regulation of pri-miRNA transcription by RNA polymerase II	15/2061	42/18723	2.18e-05	6.09e-04	15
GO:01200327	Lung	IAC	regulation of plasma membrane bounded cell projection assembly	39/2061	186/18723	5.41e-05	1.21e-03	39
GO:00604916	Lung	IAC	regulation of cell projection assembly	39/2061	188/18723	6.92e-05	1.47e-03	39
GO:0042692	Lung	IAC	muscle cell differentiation	65/2061	384/18723	2.75e-04	4.54e-03	65
GO:00456002	Lung	IAC	positive regulation of fat cell differentiation	17/2061	66/18723	6.14e-04	8.46e-03	17
GO:00454443	Lung	IAC	fat cell differentiation	42/2061	229/18723	6.19e-04	8.50e-03	42
GO:00300336	Lung	IAC	microvillus assembly	7/2061	16/18723	9.01e-04	1.11e-02	7
GO:0043403	Lung	IAC	skeletal muscle tissue regeneration	11/2061	37/18723	1.58e-03	1.66e-02	11
GO:00511462	Lung	IAC	striated muscle cell differentiation	47/2061	283/18723	2.66e-03	2.45e-02	47
GO:00310994	Lung	IAC	regeneration	34/2061	198/18723	5.73e-03	4.18e-02	34
GO:00605373	Lung	IAC	muscle tissue development	61/2061	403/18723	6.24e-03	4.48e-02	61
GO:000206413	Lung	AIS	epithelial cell development	48/1849	220/18723	1.06e-07	1.18e-05	48
GO:190165312	Lung	AIS	cellular response to peptide	65/1849	359/18723	1.05e-06	7.27e-05	65
GO:012003213	Lung	AIS	regulation of plasma membrane bounded cell projection assembly	37/1849	186/18723	2.67e-05	8.60e-04	37

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05207	Colorectum	CRC	Chemical carcinogenesis - receptor activation	42/1091	212/8465	2.62e-03	1.75e-02	1.19e-02	42
hsa052071	Colorectum	CRC	Chemical carcinogenesis - receptor activation	42/1091	212/8465	2.62e-03	1.75e-02	1.19e-02	42

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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
KLF5	MES	Cervix	CC	ZFP36L1,CTNND1,MPZL2, etc.	7.07e-01
KLF5	KER	Esophagus	Healthy	CLDN1,FAM46A,VIM, etc.	2.01e-01
KLF5	STM	Esophagus	Healthy	CLDN1,FAM46A,VIM, etc.	4.45e-01
KLF5	DUCT1	Pancreas	PDAC	LMO7,TM9SF3,CYP3A5, etc.	6.34e-01
KLF5	CD8TRM	Pancreas	ADJ	MOB3A,FAM160A1,IL3RA, etc.	0.00e+00
KLF5	CD8TEREX	Pancreas	ADJ	MOB3A,FAM160A1,IL3RA, etc.	5.23e-03
KLF5	CD8TCM	Pancreas	ADJ	MOB3A,FAM160A1,IL3RA, etc.	2.22e-16
KLF5	TREG	Pancreas	ADJ	MOB3A,FAM160A1,IL3RA, etc.	2.22e-16
KLF5	CD8TEREX	Pancreas	Healthy	MOB3A,FAM160A1,IL3RA, etc.	0.00e+00
KLF5	TREG	Pancreas	Healthy	MOB3A,FAM160A1,IL3RA, etc.	0.00e+00

∗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

KLF5

deletion

Frame_Shift_Del

novel

c.280delN

p.Lys94SerfsTer3

p.K94Sfs*3

Q13887

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

KLF5

SNV

Missense_Mutation

c.1255G>A

p.Glu419Lys

p.E419K

Q13887

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-EK-A2R8-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

KLF5

SNV

Missense_Mutation

c.604N>A

p.Glu202Lys

p.E202K

Q13887

protein_coding

tolerated(0.78)

benign(0)

TCGA-IR-A3LK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

KLF5

SNV

Missense_Mutation

c.1255N>A

p.Glu419Lys

p.E419K

Q13887

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-IR-A3LK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

KLF5

SNV

Missense_Mutation

c.341G>T

p.Arg114Leu

p.R114L

Q13887

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-IR-A3LL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

KLF5

SNV

Missense_Mutation

c.1255N>A

p.Glu419Lys

p.E419K

Q13887

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-VS-A958-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

KLF5

SNV

Missense_Mutation

c.1255N>A

p.Glu419Lys

p.E419K

Q13887

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-VS-A959-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

KLF5

SNV

Missense_Mutation

novel

c.1256N>G

p.Glu419Gly

p.E419G

Q13887

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-VS-A959-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

KLF5

SNV

Missense_Mutation

c.1255N>A

p.Glu419Lys

p.E419K

Q13887

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-VS-A9UC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

KLF5

deletion

Frame_Shift_Del

novel

c.282_288delGTATCTG

p.Tyr95HisfsTer9

p.Y95Hfs*9

Q13887

protein_coding

TCGA-JW-A5VK-01

Cervix

cervical & endocervical cancer

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
688	KLF5	TRANSCRIPTION FACTOR COMPLEX, TRANSCRIPTION FACTOR, DRUGGABLE GENOME		OUABAIN	OUABAIN
688	KLF5	TRANSCRIPTION FACTOR COMPLEX, TRANSCRIPTION FACTOR, DRUGGABLE GENOME		CID 926663	CHEMBL265686
688	KLF5	TRANSCRIPTION FACTOR COMPLEX, TRANSCRIPTION FACTOR, DRUGGABLE GENOME		CID 838877	CHEMBL405317
688	KLF5	TRANSCRIPTION FACTOR COMPLEX, TRANSCRIPTION FACTOR, DRUGGABLE GENOME		TCMDC-125567	CHEMBL530049

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