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: KCTD17

Gene summary for KCTD17

Gene summary.

Gene information	Species	Human
	Gene symbol	KCTD17
	Gene ID	79734
	Gene name	potassium channel tetramerization domain containing 17
	Gene Alias	KCTD17
	Cytomap	22q12.3
	Gene Type	protein-coding
	GO ID	GO:0006508
	UniProtAcc	Q8N5Z5

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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
79734	KCTD17	male-WTA	Human	Thyroid	PTC	4.82e-02	6.48e-02	0.1037
79734	KCTD17	PTC05	Human	Thyroid	PTC	1.05e-08	2.88e-01	0.2065
79734	KCTD17	PTC06	Human	Thyroid	PTC	1.04e-09	2.69e-01	0.2057
79734	KCTD17	PTC07	Human	Thyroid	PTC	2.29e-02	1.00e-01	0.2044
79734	KCTD17	ATC09	Human	Thyroid	ATC	1.12e-05	2.40e-01	0.2871
79734	KCTD17	ATC11	Human	Thyroid	ATC	5.90e-10	6.29e-01	0.3386
79734	KCTD17	ATC13	Human	Thyroid	ATC	2.18e-22	3.38e-01	0.34
79734	KCTD17	ATC1	Human	Thyroid	ATC	8.73e-06	2.33e-01	0.2878
79734	KCTD17	ATC2	Human	Thyroid	ATC	2.49e-06	5.36e-01	0.34
79734	KCTD17	ATC3	Human	Thyroid	ATC	6.48e-06	2.93e-01	0.338
79734	KCTD17	ATC5	Human	Thyroid	ATC	9.23e-23	3.58e-01	0.34

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:0010498113	Thyroid	PTC	proteasomal protein catabolic process	297/5968	490/18723	4.58e-40	9.63e-37	297
GO:0043161113	Thyroid	PTC	proteasome-mediated ubiquitin-dependent protein catabolic process	254/5968	412/18723	3.91e-36	4.54e-33	254
GO:0031346110	Thyroid	PTC	positive regulation of cell projection organization	173/5968	353/18723	1.09e-11	4.40e-10	173
GO:0120032111	Thyroid	PTC	regulation of plasma membrane bounded cell projection assembly	92/5968	186/18723	4.12e-07	6.83e-06	92
GO:006049120	Thyroid	PTC	regulation of cell projection assembly	92/5968	188/18723	7.55e-07	1.18e-05	92
GO:01200349	Thyroid	PTC	positive regulation of plasma membrane bounded cell projection assembly	57/5968	105/18723	1.60e-06	2.25e-05	57
GO:190211516	Thyroid	PTC	regulation of organelle assembly	88/5968	186/18723	7.41e-06	8.65e-05	88
GO:0032469111	Thyroid	PTC	endoplasmic reticulum calcium ion homeostasis	19/5968	25/18723	7.43e-06	8.65e-05	19
GO:19021176	Thyroid	PTC	positive regulation of organelle assembly	35/5968	67/18723	4.24e-04	2.83e-03	35
GO:001049832	Thyroid	ATC	proteasomal protein catabolic process	309/6293	490/18723	1.78e-41	1.13e-37	309
GO:0043161210	Thyroid	ATC	proteasome-mediated ubiquitin-dependent protein catabolic process	265/6293	412/18723	7.09e-38	1.49e-34	265
GO:003134623	Thyroid	ATC	positive regulation of cell projection organization	186/6293	353/18723	7.99e-14	4.23e-12	186
GO:012003414	Thyroid	ATC	positive regulation of plasma membrane bounded cell projection assembly	60/6293	105/18723	6.10e-07	8.47e-06	60
GO:012003223	Thyroid	ATC	regulation of plasma membrane bounded cell projection assembly	95/6293	186/18723	6.13e-07	8.49e-06	95
GO:0060491111	Thyroid	ATC	regulation of cell projection assembly	95/6293	188/18723	1.14e-06	1.47e-05	95
GO:003246925	Thyroid	ATC	endoplasmic reticulum calcium ion homeostasis	19/6293	25/18723	1.77e-05	1.62e-04	19
GO:190211522	Thyroid	ATC	regulation of organelle assembly	90/6293	186/18723	2.00e-05	1.81e-04	90
GO:190211713	Thyroid	ATC	positive regulation of organelle assembly	36/6293	67/18723	5.41e-04	3.13e-03	36

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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

KCTD17

SNV

Missense_Mutation

c.497N>A

p.Arg166His

p.R166H

Q8N5Z5

protein_coding

deleterious(0)

possibly_damaging(0.454)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

KCTD17

SNV

Missense_Mutation

novel

c.748N>A

p.Asp250Asn

p.D250N

Q8N5Z5

protein_coding

deleterious_low_confidence(0.04)

benign(0.173)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

KCTD17

SNV

Missense_Mutation

novel

c.912N>T

p.Glu304Asp

p.E304D

Q8N5Z5

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.935)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

KCTD17

SNV

Missense_Mutation

novel

c.560N>G

p.Phe187Cys

p.F187C

Q8N5Z5

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-AP-A1DP-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

paclitaxel

KCTD17

SNV

Missense_Mutation

c.337N>A

p.Glu113Lys

p.E113K

Q8N5Z5

protein_coding

deleterious(0.03)

probably_damaging(0.982)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

KCTD17

SNV

Missense_Mutation

c.334G>A

p.Ala112Thr

p.A112T

Q8N5Z5

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-BK-A139-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

KCTD17

SNV

Missense_Mutation

c.538N>A

p.Gly180Ser

p.G180S

Q8N5Z5

protein_coding

deleterious(0.03)

possibly_damaging(0.664)

TCGA-D1-A103-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

KCTD17

SNV

Missense_Mutation

novel

c.692N>C

p.Glu231Ala

p.E231A

Q8N5Z5

protein_coding

deleterious_low_confidence(0.01)

benign(0.005)

TCGA-EC-A1NJ-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

KCTD17

SNV

Missense_Mutation

novel

c.239N>A

p.Arg80His

p.R80H

Q8N5Z5

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-EO-A22U-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

KCTD17

SNV

Missense_Mutation

novel

c.601N>T

p.Gly201Trp

p.G201W

Q8N5Z5

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-05-4396-01

Lung

lung adenocarcinoma

Male

>=65

III/IV

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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