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: KLF10

Gene summary for KLF10

Gene summary.

Gene information	Species	Human
	Gene symbol	KLF10
	Gene ID	7071
	Gene name	Kruppel like factor 10
	Gene Alias	EGR-alpha
	Cytomap	8q22.3
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	Q13118

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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
7071	KLF10	LZE7T	Human	Esophagus	ESCC	6.18e-10	-3.26e-01	0.0667
7071	KLF10	LZE8T	Human	Esophagus	ESCC	1.93e-06	8.14e-01	0.067
7071	KLF10	LZE22D1	Human	Esophagus	HGIN	2.05e-02	-5.50e-01	0.0595
7071	KLF10	LZE24T	Human	Esophagus	ESCC	3.61e-13	1.23e+00	0.0596
7071	KLF10	LZE6T	Human	Esophagus	ESCC	1.69e-04	-4.05e-01	0.0845
7071	KLF10	P1T-E	Human	Esophagus	ESCC	4.98e-08	1.19e+00	0.0875
7071	KLF10	P2T-E	Human	Esophagus	ESCC	9.74e-34	1.09e+00	0.1177
7071	KLF10	P4T-E	Human	Esophagus	ESCC	2.73e-11	6.80e-01	0.1323
7071	KLF10	P5T-E	Human	Esophagus	ESCC	1.89e-15	6.75e-01	0.1327
7071	KLF10	P8T-E	Human	Esophagus	ESCC	1.40e-33	1.20e+00	0.0889
7071	KLF10	P9T-E	Human	Esophagus	ESCC	1.99e-03	1.36e-01	0.1131
7071	KLF10	P10T-E	Human	Esophagus	ESCC	2.72e-13	8.09e-01	0.116
7071	KLF10	P11T-E	Human	Esophagus	ESCC	6.67e-17	1.41e+00	0.1426
7071	KLF10	P12T-E	Human	Esophagus	ESCC	1.00e-27	1.45e+00	0.1122
7071	KLF10	P15T-E	Human	Esophagus	ESCC	3.89e-18	8.72e-01	0.1149
7071	KLF10	P16T-E	Human	Esophagus	ESCC	4.44e-14	6.58e-01	0.1153
7071	KLF10	P20T-E	Human	Esophagus	ESCC	1.78e-34	1.71e+00	0.1124
7071	KLF10	P21T-E	Human	Esophagus	ESCC	1.38e-17	8.89e-01	0.1617
7071	KLF10	P22T-E	Human	Esophagus	ESCC	1.10e-06	4.16e-01	0.1236
7071	KLF10	P23T-E	Human	Esophagus	ESCC	6.83e-36	2.10e+00	0.108

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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
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:00198277	Esophagus	HGIN	stem cell population maintenance	39/2587	131/18723	1.63e-06	6.14e-05	39
GO:00987278	Esophagus	HGIN	maintenance of cell number	39/2587	134/18723	3.02e-06	1.03e-04	39
GO:003009927	Esophagus	HGIN	myeloid cell differentiation	83/2587	381/18723	1.26e-05	3.52e-04	83
GO:007149626	Esophagus	HGIN	cellular response to external stimulus	71/2587	320/18723	2.77e-05	7.19e-04	71
GO:003166820	Esophagus	HGIN	cellular response to extracellular stimulus	56/2587	246/18723	9.05e-05	1.97e-03	56
GO:004563725	Esophagus	HGIN	regulation of myeloid cell differentiation	49/2587	210/18723	1.28e-04	2.61e-03	49
GO:00027617	Esophagus	HGIN	regulation of myeloid leukocyte differentiation	31/2587	120/18723	3.35e-04	5.50e-03	31
GO:003166920	Esophagus	HGIN	cellular response to nutrient levels	47/2587	215/18723	8.20e-04	1.07e-02	47
GO:000257316	Esophagus	HGIN	myeloid leukocyte differentiation	45/2587	208/18723	1.31e-03	1.56e-02	45
GO:004563917	Esophagus	HGIN	positive regulation of myeloid cell differentiation	26/2587	103/18723	1.40e-03	1.63e-02	26
GO:003166726	Esophagus	HGIN	response to nutrient levels	89/2587	474/18723	1.41e-03	1.64e-02	89
GO:000762318	Esophagus	HGIN	circadian rhythm	45/2587	210/18723	1.60e-03	1.79e-02	45
GO:0035019	Esophagus	HGIN	somatic stem cell population maintenance	13/2587	42/18723	3.32e-03	3.12e-02	13
GO:190165318	Esophagus	HGIN	cellular response to peptide	68/2587	359/18723	3.88e-03	3.54e-02	68
GO:000926719	Esophagus	HGIN	cellular response to starvation	34/2587	156/18723	4.21e-03	3.77e-02	34
GO:004259418	Esophagus	HGIN	response to starvation	41/2587	197/18723	4.34e-03	3.84e-02	41
GO:00027633	Esophagus	HGIN	positive regulation of myeloid leukocyte differentiation	16/2587	58/18723	4.35e-03	3.84e-02	16
GO:190370620	Esophagus	HGIN	regulation of hemopoiesis	69/2587	367/18723	4.39e-03	3.86e-02	69
GO:000150316	Esophagus	HGIN	ossification	75/2587	408/18723	5.49e-03	4.49e-02	75
GO:0071496111	Esophagus	ESCC	cellular response to external stimulus	215/8552	320/18723	4.29e-15	2.43e-13	215

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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
KLF10	DC	Breast	ADJ	PABPC4,CD83,IRF2BP2, etc.	4.95e-02
KLF10	INMON	Cervix	CC	CCL3L1,AZIN1-AS1,C15orf48, etc.	1.98e-01
KLF10	MON	Cervix	CC	CCL3L1,AZIN1-AS1,C15orf48, etc.	2.13e-01
KLF10	INMON	Cervix	HSIL_HPV	CCL3L1,AZIN1-AS1,C15orf48, etc.	1.65e-01
KLF10	MAC	Colorectum	CRC	ZSCAN5A,FOXK2,BRD1, etc.	3.32e-01
KLF10	MON	Colorectum	CRC	ZSCAN5A,FOXK2,BRD1, etc.	2.70e-01
KLF10	MAC	Colorectum	Healthy	ZSCAN5A,FOXK2,BRD1, etc.	4.38e-01
KLF10	MON	Colorectum	Healthy	ZSCAN5A,FOXK2,BRD1, etc.	1.15e-01
KLF10	MAST	Endometrium	ADJ	MIIP,TJP2,MAPKAPK2, etc.	1.02e-01
KLF10	MAST	Endometrium	EEC	MIIP,TJP2,MAPKAPK2, etc.	7.73e-02

∗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

KLF10

SNV

Missense_Mutation

rs749961016

c.551N>A

p.Ser184Tyr

p.S184Y

Q13118

protein_coding

tolerated(0.98)

benign(0.259)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

KLF10

SNV

Missense_Mutation

novel

c.442N>T

p.Pro148Ser

p.P148S

Q13118

protein_coding

tolerated(0.23)

benign(0.015)

TCGA-BH-A0AV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

KLF10

SNV

Missense_Mutation

novel

c.22N>G

p.Leu8Val

p.L8V

Q13118

protein_coding

tolerated_low_confidence(0.07)

benign(0.014)

TCGA-OL-A5RW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

KLF10

insertion

In_Frame_Ins

novel

c.1054_1055insATCAAAACTTGGACCCTTGGAAAACAAAAGTTTTAATTA

p.Pro352delinsHisGlnAsnLeuAspProTrpLysThrLysValLeuIleThr

p.P352delinsHQNLDPWKTKVLIT

Q13118

protein_coding

TCGA-A8-A0A4-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

KLF10

insertion

In_Frame_Ins

novel

c.578_579insCCCACACAG

p.Val193_Glu194insProHisSer

p.V193_E194insPHS

Q13118

protein_coding

TCGA-AN-A04C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

KLF10

insertion

Frame_Shift_Ins

novel

c.577_578insACATTGCTCTACCTCCAACCCCTGC

p.Val193AspfsTer10

p.V193Dfs*10

Q13118

protein_coding

TCGA-AN-A04C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

KLF10

insertion

Nonsense_Mutation

novel

c.1065_1066insTGAACTGAGTTCGCCCTCCC

p.Lys356Ter

p.K356*

Q13118

protein_coding

TCGA-B6-A0RG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

KLF10

insertion

Nonsense_Mutation

novel

c.60_61insTTCCAGTCAACATCGTGGATGTAGTGATTAA

p.Glu21PhefsTer8

p.E21Ffs*8

Q13118

protein_coding

TCGA-BH-A0BA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

KLF10

SNV

Missense_Mutation

novel

c.938N>T

p.Pro313Leu

p.P313L

Q13118

protein_coding

deleterious(0)

possibly_damaging(0.665)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

KLF10

SNV

Missense_Mutation

novel

c.290N>A

p.Ser97Asn

p.S97N

Q13118

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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

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