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	EEC-subject4	Human	Endometrium	EEC	4.33e-03	3.25e-01	-0.2571
688	KLF5	EEC-subject5	Human	Endometrium	EEC	4.47e-06	4.07e-01	-0.249
688	KLF5	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	1.04e-13	4.89e-01	-0.1869
688	KLF5	GSM6177620_NYU_UCEC1_lib2_lib2	Human	Endometrium	EEC	5.08e-17	5.85e-01	-0.1875
688	KLF5	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	2.35e-17	5.42e-01	-0.1883
688	KLF5	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	1.21e-15	5.80e-01	-0.1934
688	KLF5	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	6.54e-23	5.71e-01	-0.1917
688	KLF5	GSM6177622_NYU_UCEC3_lib2_lib2	Human	Endometrium	EEC	1.28e-20	5.64e-01	-0.1916
688	KLF5	GSM6177623_NYU_UCEC3_Vis	Human	Endometrium	EEC	6.31e-04	4.04e-01	-0.1269
688	KLF5	LZE20T	Human	Esophagus	ESCC	5.26e-11	1.11e+00	0.0662
688	KLF5	LZE22T	Human	Esophagus	ESCC	1.48e-04	1.32e+00	0.068
688	KLF5	LZE24D1	Human	Esophagus	HGIN	6.73e-09	1.44e+00	0.054
688	KLF5	LZE24T	Human	Esophagus	ESCC	8.97e-31	2.29e+00	0.0596
688	KLF5	LZE21T	Human	Esophagus	ESCC	1.17e-16	1.76e+00	0.0655
688	KLF5	LZE6T	Human	Esophagus	ESCC	8.43e-07	-8.27e-01	0.0845
688	KLF5	P1T-E	Human	Esophagus	ESCC	1.02e-30	2.41e+00	0.0875
688	KLF5	P2T-E	Human	Esophagus	ESCC	6.48e-14	6.77e-01	0.1177
688	KLF5	P4T-E	Human	Esophagus	ESCC	2.27e-36	2.25e+00	0.1323
688	KLF5	P8T-E	Human	Esophagus	ESCC	6.17e-51	2.07e+00	0.0889
688	KLF5	P9T-E	Human	Esophagus	ESCC	5.30e-46	2.18e+00	0.1131

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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:00454445	Cervix	CC	fat cell differentiation	53/2311	229/18723	3.72e-06	9.75e-05	53
GO:00616148	Cervix	CC	pri-miRNA transcription by RNA polymerase II	20/2311	55/18723	4.22e-06	1.09e-04	20
GO:19028938	Cervix	CC	regulation of pri-miRNA transcription by RNA polymerase II	19/2311	54/18723	1.27e-05	2.60e-04	19
GO:00310996	Cervix	CC	regeneration	46/2311	198/18723	1.43e-05	2.84e-04	46
GO:19016538	Cervix	CC	cellular response to peptide	72/2311	359/18723	1.89e-05	3.48e-04	72
GO:19028955	Cervix	CC	positive regulation of pri-miRNA transcription by RNA polymerase II	15/2311	42/18723	8.42e-05	1.13e-03	15
GO:00605375	Cervix	CC	muscle tissue development	76/2311	403/18723	9.76e-05	1.27e-03	76
GO:00147064	Cervix	CC	striated muscle tissue development	72/2311	384/18723	1.76e-04	2.07e-03	72
GO:000206410	Cervix	CC	epithelial cell development	45/2311	220/18723	4.14e-04	4.21e-03	45
GO:0045598	Cervix	CC	regulation of fat cell differentiation	31/2311	139/18723	7.06e-04	6.41e-03	31
GO:00456004	Cervix	CC	positive regulation of fat cell differentiation	18/2311	66/18723	8.09e-04	7.07e-03	18
GO:00426924	Cervix	CC	muscle cell differentiation	69/2311	384/18723	8.12e-04	7.09e-03	69
GO:0042246	Cervix	CC	tissue regeneration	19/2311	72/18723	9.11e-04	7.81e-03	19
GO:01200328	Cervix	CC	regulation of plasma membrane bounded cell projection assembly	38/2311	186/18723	1.14e-03	9.35e-03	38
GO:00434032	Cervix	CC	skeletal muscle tissue regeneration	12/2311	37/18723	1.15e-03	9.39e-03	12
GO:00604917	Cervix	CC	regulation of cell projection assembly	38/2311	188/18723	1.40e-03	1.10e-02	38
GO:00300337	Cervix	CC	microvillus assembly	7/2311	16/18723	1.79e-03	1.34e-02	7
GO:19908234	Cervix	CC	response to leukemia inhibitory factor	22/2311	95/18723	2.40e-03	1.70e-02	22
GO:00075173	Cervix	CC	muscle organ development	58/2311	327/18723	2.73e-03	1.85e-02	58
GO:19908304	Cervix	CC	cellular response to leukemia inhibitory factor	21/2311	94/18723	4.68e-03	2.82e-02	21

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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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