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: ICK

Gene summary for ICK

Gene summary.

Gene information	Species	Human
	Gene symbol	ICK
	Gene ID	22858
	Gene name	ciliogenesis associated kinase 1
	Gene Alias	ECO
	Cytomap	6p12.1
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	A0A024RD59

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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
22858	ICK	LZE2D	Human	Esophagus	HGIN	8.16e-03	4.22e-01	0.0642
22858	ICK	LZE2T	Human	Esophagus	ESCC	4.21e-05	1.13e+00	0.082
22858	ICK	LZE4T	Human	Esophagus	ESCC	3.24e-08	1.78e-01	0.0811
22858	ICK	LZE5T	Human	Esophagus	ESCC	1.81e-03	4.51e-01	0.0514
22858	ICK	LZE7T	Human	Esophagus	ESCC	4.11e-11	6.09e-01	0.0667
22858	ICK	LZE8T	Human	Esophagus	ESCC	5.97e-04	6.92e-02	0.067
22858	ICK	LZE20T	Human	Esophagus	ESCC	5.26e-05	2.78e-01	0.0662
22858	ICK	LZE24T	Human	Esophagus	ESCC	2.22e-16	4.97e-01	0.0596
22858	ICK	LZE21T	Human	Esophagus	ESCC	3.36e-07	3.86e-01	0.0655
22858	ICK	P1T-E	Human	Esophagus	ESCC	2.28e-07	4.15e-01	0.0875
22858	ICK	P2T-E	Human	Esophagus	ESCC	1.43e-15	3.08e-01	0.1177
22858	ICK	P4T-E	Human	Esophagus	ESCC	6.71e-31	7.56e-01	0.1323
22858	ICK	P5T-E	Human	Esophagus	ESCC	2.98e-03	7.61e-02	0.1327
22858	ICK	P8T-E	Human	Esophagus	ESCC	9.58e-14	2.75e-01	0.0889
22858	ICK	P9T-E	Human	Esophagus	ESCC	9.95e-20	4.63e-01	0.1131
22858	ICK	P10T-E	Human	Esophagus	ESCC	7.51e-16	3.66e-01	0.116
22858	ICK	P11T-E	Human	Esophagus	ESCC	2.23e-04	1.88e-01	0.1426
22858	ICK	P12T-E	Human	Esophagus	ESCC	8.75e-31	8.12e-01	0.1122
22858	ICK	P15T-E	Human	Esophagus	ESCC	1.10e-14	2.92e-01	0.1149
22858	ICK	P16T-E	Human	Esophagus	ESCC	8.31e-19	4.04e-01	0.1153

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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
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:0031331210	Thyroid	ATC	positive regulation of cellular catabolic process	258/6293	427/18723	2.09e-30	1.65e-27	258
GO:004217635	Thyroid	ATC	regulation of protein catabolic process	239/6293	391/18723	2.63e-29	1.85e-26	239
GO:007259429	Thyroid	ATC	establishment of protein localization to organelle	247/6293	422/18723	2.88e-26	1.40e-23	247
GO:190336235	Thyroid	ATC	regulation of cellular protein catabolic process	168/6293	255/18723	3.50e-26	1.58e-23	168
GO:190305035	Thyroid	ATC	regulation of proteolysis involved in cellular protein catabolic process	146/6293	221/18723	4.18e-23	1.20e-20	146
GO:006113633	Thyroid	ATC	regulation of proteasomal protein catabolic process	128/6293	187/18723	1.63e-22	4.30e-20	128
GO:2000058210	Thyroid	ATC	regulation of ubiquitin-dependent protein catabolic process	116/6293	164/18723	2.15e-22	5.43e-20	116
GO:0032434210	Thyroid	ATC	regulation of proteasomal ubiquitin-dependent protein catabolic process	100/6293	134/18723	2.41e-22	5.86e-20	100
GO:0045732210	Thyroid	ATC	positive regulation of protein catabolic process	148/6293	231/18723	1.93e-21	4.36e-19	148
GO:003450423	Thyroid	ATC	protein localization to nucleus	175/6293	290/18723	6.23e-21	1.23e-18	175
GO:000691326	Thyroid	ATC	nucleocytoplasmic transport	180/6293	301/18723	6.97e-21	1.30e-18	180
GO:005116926	Thyroid	ATC	nuclear transport	180/6293	301/18723	6.97e-21	1.30e-18	180
GO:190336434	Thyroid	ATC	positive regulation of cellular protein catabolic process	109/6293	155/18723	8.26e-21	1.49e-18	109
GO:190332034	Thyroid	ATC	regulation of protein modification by small protein conjugation or removal	152/6293	242/18723	9.76e-21	1.71e-18	152
GO:190180027	Thyroid	ATC	positive regulation of proteasomal protein catabolic process	85/6293	114/18723	3.70e-19	5.20e-17	85
GO:003139634	Thyroid	ATC	regulation of protein ubiquitination	132/6293	210/18723	3.13e-18	3.98e-16	132
GO:003243627	Thyroid	ATC	positive regulation of proteasomal ubiquitin-dependent protein catabolic process	70/6293	90/18723	9.72e-18	1.10e-15	70
GO:190305227	Thyroid	ATC	positive regulation of proteolysis involved in cellular protein catabolic process	93/6293	133/18723	1.06e-17	1.18e-15	93
GO:001605525	Thyroid	ATC	Wnt signaling pathway	234/6293	444/18723	4.64e-17	4.31e-15	234
GO:019873825	Thyroid	ATC	cell-cell signaling by wnt	234/6293	446/18723	9.26e-17	8.25e-15	234

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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

ICK

SNV

Missense_Mutation

novel

c.1348G>C

p.Glu450Gln

p.E450Q

Q9UPZ9

protein_coding

tolerated(0.15)

benign(0.015)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

ICK

SNV

Missense_Mutation

novel

c.1126N>C

p.Ser376Pro

p.S376P

Q9UPZ9

protein_coding

tolerated(0.14)

benign(0.009)

TCGA-A2-A1G4-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

adriamycin

ICK

SNV

Missense_Mutation

novel

c.1126T>C

p.Ser376Pro

p.S376P

Q9UPZ9

protein_coding

tolerated(0.14)

benign(0.009)

TCGA-A8-A06R-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

5-fluorouracil

ICK

SNV

Missense_Mutation

c.613G>A

p.Glu205Lys

p.E205K

Q9UPZ9

protein_coding

deleterious(0)

probably_damaging(0.969)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ICK

SNV

Missense_Mutation

rs561765544

c.995G>A

p.Arg332Gln

p.R332Q

Q9UPZ9

protein_coding

tolerated(0.52)

benign(0.007)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ICK

SNV

Missense_Mutation

c.932N>T

p.Ala311Val

p.A311V

Q9UPZ9

protein_coding

tolerated(0.31)

benign(0.001)

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ICK

SNV

Missense_Mutation

novel

c.1126N>C

p.Ser376Pro

p.S376P

Q9UPZ9

protein_coding

tolerated(0.14)

benign(0.009)

TCGA-BH-A1FH-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

ICK

SNV

Missense_Mutation

novel

c.1126T>C

p.Ser376Pro

p.S376P

Q9UPZ9

protein_coding

tolerated(0.14)

benign(0.009)

TCGA-C8-A273-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

ICK

SNV

Missense_Mutation

novel

c.1126N>C

p.Ser376Pro

p.S376P

Q9UPZ9

protein_coding

tolerated(0.14)

benign(0.009)

TCGA-D8-A1JT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

ICK

SNV

Missense_Mutation

novel

c.1126N>C

p.Ser376Pro

p.S376P

Q9UPZ9

protein_coding

tolerated(0.14)

benign(0.009)

TCGA-D8-A1XG-01

Breast

breast invasive carcinoma

Female

>=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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