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: KLHL2

Gene summary for KLHL2

Gene summary.

Gene information	Species	Human
	Gene symbol	KLHL2
	Gene ID	11275
	Gene name	kelch like family member 2
	Gene Alias	ABP-KELCH
	Cytomap	4q32.3
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	O95198

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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
11275	KLHL2	CCI_1	Human	Cervix	CC	1.29e-02	5.89e-01	0.528
11275	KLHL2	CCI_2	Human	Cervix	CC	4.68e-04	9.53e-01	0.5249
11275	KLHL2	CCI_3	Human	Cervix	CC	1.68e-04	5.80e-01	0.516
11275	KLHL2	HTA12-15-2	Human	Pancreas	PDAC	3.81e-02	3.41e-01	0.2315
11275	KLHL2	HTA12-25-1	Human	Pancreas	PDAC	1.12e-07	7.86e-01	0.313
11275	KLHL2	HTA12-26-1	Human	Pancreas	PDAC	2.80e-17	8.93e-01	0.3728
11275	KLHL2	HTA12-29-1	Human	Pancreas	PDAC	5.12e-18	4.96e-01	0.3722

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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

∗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:001049810	Cervix	CC	proteasomal protein catabolic process	111/2311	490/18723	8.98e-11	1.58e-08	111
GO:004316110	Cervix	CC	proteasome-mediated ubiquitin-dependent protein catabolic process	91/2311	412/18723	1.65e-08	1.25e-06	91
GO:00002097	Cervix	CC	protein polyubiquitination	58/2311	236/18723	1.57e-07	7.41e-06	58
GO:00068927	Cervix	CC	post-Golgi vesicle-mediated transport	28/2311	104/18723	4.31e-05	6.61e-04	28
GO:00481938	Cervix	CC	Golgi vesicle transport	58/2311	296/18723	2.24e-04	2.54e-03	58
GO:19023059	Cervix	CC	regulation of sodium ion transmembrane transport	19/2311	68/18723	4.21e-04	4.25e-03	19
GO:00451043	Cervix	CC	intermediate filament cytoskeleton organization	15/2311	51/18723	9.25e-04	7.84e-03	15
GO:00451033	Cervix	CC	intermediate filament-based process	15/2311	52/18723	1.15e-03	9.39e-03	15
GO:00020288	Cervix	CC	regulation of sodium ion transport	21/2311	90/18723	2.71e-03	1.85e-02	21
GO:20006498	Cervix	CC	regulation of sodium ion transmembrane transporter activity	15/2311	58/18723	3.75e-03	2.38e-02	15
GO:00164827	Cervix	CC	cytosolic transport	33/2311	168/18723	4.43e-03	2.70e-02	33
GO:00518656	Cervix	CC	protein autoubiquitination	17/2311	73/18723	6.71e-03	3.70e-02	17
GO:0002028	Colorectum	AD	regulation of sodium ion transport	36/3918	90/18723	2.89e-05	5.37e-04	36
GO:1902305	Colorectum	AD	regulation of sodium ion transmembrane transport	27/3918	68/18723	3.19e-04	3.80e-03	27
GO:0051865	Colorectum	AD	protein autoubiquitination	28/3918	73/18723	4.87e-04	5.30e-03	28
GO:2000649	Colorectum	AD	regulation of sodium ion transmembrane transporter activity	23/3918	58/18723	8.82e-04	8.53e-03	23
GO:00020282	Colorectum	MSS	regulation of sodium ion transport	32/3467	90/18723	9.56e-05	1.50e-03	32
GO:19023052	Colorectum	MSS	regulation of sodium ion transmembrane transport	26/3467	68/18723	1.08e-04	1.68e-03	26
GO:20006492	Colorectum	MSS	regulation of sodium ion transmembrane transporter activity	22/3467	58/18723	4.06e-04	4.99e-03	22
GO:00518651	Colorectum	MSS	protein autoubiquitination	25/3467	73/18723	1.00e-03	1.00e-02	25

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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

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

KLHL2

SNV

Missense_Mutation

c.359N>T

p.Thr120Ile

p.T120I

O95198

protein_coding

deleterious(0.01)

possibly_damaging(0.461)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

KLHL2

deletion

Frame_Shift_Del

novel

c.20delN

p.Gln9ArgfsTer28

p.Q9Rfs*28

O95198

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

KLHL2

SNV

Missense_Mutation

novel

c.575T>C

p.Val192Ala

p.V192A

O95198

protein_coding

deleterious(0.03)

possibly_damaging(0.895)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

KLHL2

SNV

Missense_Mutation

novel

c.1390C>T

p.Arg464Cys

p.R464C

O95198

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

KLHL2

SNV

Missense_Mutation

c.1525N>C

p.Asp509His

p.D509H

O95198

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-C5-A1BK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

KLHL2

SNV

Missense_Mutation

c.1170N>A

p.Met390Ile

p.M390I

O95198

protein_coding

deleterious(0)

probably_damaging(0.987)

TCGA-C5-A1MK-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

carboplatin

KLHL2

SNV

Missense_Mutation

rs770856919

c.905N>A

p.Arg302Gln

p.R302Q

O95198

protein_coding

deleterious(0.05)

benign(0.285)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

KLHL2

SNV

Missense_Mutation

c.1237N>C

p.Asp413His

p.D413H

O95198

protein_coding

deleterious(0.01)

probably_damaging(0.992)

TCGA-EK-A3GK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

KLHL2

SNV

Missense_Mutation

novel

c.1435G>C

p.Glu479Gln

p.E479Q

O95198

protein_coding

tolerated(0.33)

benign(0.043)

TCGA-MA-AA41-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

KLHL2

SNV

Missense_Mutation

novel

c.726N>A

p.Met242Ile

p.M242I

O95198

protein_coding

tolerated(0.12)

benign(0.026)

TCGA-A6-2686-01

Colorectum

colon adenocarcinoma

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

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