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: KCTD10

Gene summary for KCTD10

Gene summary.

Gene information	Species	Human
	Gene symbol	KCTD10
	Gene ID	83892
	Gene name	potassium channel tetramerization domain containing 10
	Gene Alias	BTBD28
	Cytomap	12q24.11
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	Q9H3F6

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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
83892	KCTD10	LZE4T	Human	Esophagus	ESCC	1.10e-02	6.33e-02	0.0811
83892	KCTD10	LZE7T	Human	Esophagus	ESCC	8.72e-06	2.02e-01	0.0667
83892	KCTD10	LZE24T	Human	Esophagus	ESCC	2.34e-04	9.95e-02	0.0596
83892	KCTD10	P1T-E	Human	Esophagus	ESCC	4.51e-02	8.54e-02	0.0875
83892	KCTD10	P2T-E	Human	Esophagus	ESCC	6.74e-16	2.88e-01	0.1177
83892	KCTD10	P4T-E	Human	Esophagus	ESCC	4.64e-11	1.86e-01	0.1323
83892	KCTD10	P5T-E	Human	Esophagus	ESCC	8.70e-08	9.18e-02	0.1327
83892	KCTD10	P8T-E	Human	Esophagus	ESCC	1.13e-14	1.50e-01	0.0889
83892	KCTD10	P10T-E	Human	Esophagus	ESCC	4.79e-05	3.07e-02	0.116
83892	KCTD10	P11T-E	Human	Esophagus	ESCC	8.01e-05	2.50e-01	0.1426
83892	KCTD10	P12T-E	Human	Esophagus	ESCC	1.12e-04	3.33e-02	0.1122
83892	KCTD10	P15T-E	Human	Esophagus	ESCC	5.62e-07	2.06e-01	0.1149
83892	KCTD10	P16T-E	Human	Esophagus	ESCC	1.13e-15	2.06e-01	0.1153
83892	KCTD10	P20T-E	Human	Esophagus	ESCC	1.38e-06	6.00e-02	0.1124
83892	KCTD10	P21T-E	Human	Esophagus	ESCC	5.16e-14	2.93e-01	0.1617
83892	KCTD10	P22T-E	Human	Esophagus	ESCC	5.16e-09	1.15e-01	0.1236
83892	KCTD10	P23T-E	Human	Esophagus	ESCC	7.63e-09	1.43e-01	0.108
83892	KCTD10	P24T-E	Human	Esophagus	ESCC	2.83e-07	1.15e-01	0.1287
83892	KCTD10	P26T-E	Human	Esophagus	ESCC	3.39e-08	1.25e-01	0.1276
83892	KCTD10	P27T-E	Human	Esophagus	ESCC	2.25e-11	1.49e-01	0.1055

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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
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:000726510	Esophagus	ESCC	Ras protein signal transduction	201/8552	337/18723	1.44e-07	2.30e-06	201
GO:000726610	Esophagus	ESCC	Rho protein signal transduction	81/8552	137/18723	1.03e-03	5.20e-03	81
GO:00465789	Esophagus	ESCC	regulation of Ras protein signal transduction	106/8552	189/18723	2.49e-03	1.08e-02	106
GO:00512592	Esophagus	ESCC	protein complex oligomerization	130/8552	238/18723	3.29e-03	1.36e-02	130
GO:005105610	Esophagus	ESCC	regulation of small GTPase mediated signal transduction	157/8552	302/18723	1.55e-02	4.98e-02	157
GO:001049822	Liver	HCC	proteasomal protein catabolic process	351/7958	490/18723	6.92e-40	1.46e-36	351
GO:004316122	Liver	HCC	proteasome-mediated ubiquitin-dependent protein catabolic process	299/7958	412/18723	7.82e-36	8.27e-33	299
GO:000726521	Liver	HCC	Ras protein signal transduction	187/7958	337/18723	8.89e-07	1.35e-05	187
GO:000726621	Liver	HCC	Rho protein signal transduction	76/7958	137/18723	1.46e-03	7.75e-03	76
GO:004657811	Liver	HCC	regulation of Ras protein signal transduction	100/7958	189/18723	2.42e-03	1.18e-02	100
GO:00350242	Liver	HCC	negative regulation of Rho protein signal transduction	16/7958	22/18723	4.03e-03	1.76e-02	16
GO:001049820	Oral cavity	OSCC	proteasomal protein catabolic process	336/7305	490/18723	5.45e-41	8.63e-38	336
GO:004316120	Oral cavity	OSCC	proteasome-mediated ubiquitin-dependent protein catabolic process	285/7305	412/18723	5.68e-36	5.99e-33	285
GO:00072659	Oral cavity	OSCC	Ras protein signal transduction	185/7305	337/18723	1.95e-09	4.60e-08	185
GO:00072669	Oral cavity	OSCC	Rho protein signal transduction	76/7305	137/18723	6.64e-05	5.37e-04	76
GO:0051259	Oral cavity	OSCC	protein complex oligomerization	121/7305	238/18723	1.29e-04	9.21e-04	121
GO:00350245	Oral cavity	OSCC	negative regulation of Rho protein signal transduction	16/7305	22/18723	1.40e-03	6.79e-03	16
GO:00465788	Oral cavity	OSCC	regulation of Ras protein signal transduction	90/7305	189/18723	9.58e-03	3.40e-02	90

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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

KCTD10

SNV

Missense_Mutation

c.751N>A

p.Glu251Lys

p.E251K

Q9H3F6

protein_coding

deleterious(0)

probably_damaging(0.957)

TCGA-AC-A3W6-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

KCTD10

SNV

Missense_Mutation

rs369957720

c.889N>A

p.Val297Met

p.V297M

Q9H3F6

protein_coding

deleterious_low_confidence(0.04)

probably_damaging(0.994)

TCGA-AC-A3W7-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

KCTD10

SNV

Missense_Mutation

c.512N>C

p.Lys171Thr

p.K171T

Q9H3F6

protein_coding

tolerated(0.05)

probably_damaging(0.986)

TCGA-B6-A0WS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

KCTD10

SNV

Missense_Mutation

c.727N>A

p.Glu243Lys

p.E243K

Q9H3F6

protein_coding

deleterious(0)

probably_damaging(0.947)

TCGA-D8-A1JN-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozolum

KCTD10

SNV

Missense_Mutation

c.374N>G

p.Gln125Arg

p.Q125R

Q9H3F6

protein_coding

tolerated(0.07)

benign(0.009)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

KCTD10

insertion

In_Frame_Ins

novel

c.489_490insACCTCGAACAAAAAGCAAATGAGAAGAAATCATCAC

p.Leu163_Leu164insThrSerAsnLysLysGlnMetArgArgAsnHisHis

p.L163_L164insTSNKKQMRRNHH

Q9H3F6

protein_coding

TCGA-AN-A041-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

KCTD10

SNV

Missense_Mutation

novel

c.195N>A

p.Met65Ile

p.M65I

Q9H3F6

protein_coding

tolerated(0.22)

benign(0.145)

TCGA-Q1-A5R2-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

KCTD10

SNV

Missense_Mutation

c.706N>A

p.Glu236Lys

p.E236K

Q9H3F6

protein_coding

deleterious(0)

probably_damaging(0.928)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

KCTD10

SNV

Missense_Mutation

c.657G>C

p.Gln219His

p.Q219H

Q9H3F6

protein_coding

tolerated(0.54)

benign(0.001)

TCGA-VS-A8QH-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

gemcitabine

KCTD10

SNV

Missense_Mutation

rs200831911

c.872N>A

p.Arg291Gln

p.R291Q

Q9H3F6

protein_coding

tolerated_low_confidence(0.32)

benign(0.262)

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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