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	P17T-E	Human	Esophagus	ESCC	9.54e-03	1.59e-01	0.1278
22858	ICK	P19T-E	Human	Esophagus	ESCC	8.75e-04	1.86e-01	0.1662
22858	ICK	P20T-E	Human	Esophagus	ESCC	7.88e-25	5.12e-01	0.1124
22858	ICK	P21T-E	Human	Esophagus	ESCC	9.10e-11	2.15e-01	0.1617
22858	ICK	P22T-E	Human	Esophagus	ESCC	3.42e-21	4.08e-01	0.1236
22858	ICK	P23T-E	Human	Esophagus	ESCC	2.59e-25	6.65e-01	0.108
22858	ICK	P24T-E	Human	Esophagus	ESCC	2.43e-14	1.02e-01	0.1287
22858	ICK	P26T-E	Human	Esophagus	ESCC	3.07e-20	4.81e-01	0.1276
22858	ICK	P27T-E	Human	Esophagus	ESCC	1.33e-39	7.13e-01	0.1055
22858	ICK	P28T-E	Human	Esophagus	ESCC	3.18e-32	9.45e-01	0.1149
22858	ICK	P30T-E	Human	Esophagus	ESCC	1.70e-30	1.13e+00	0.137
22858	ICK	P31T-E	Human	Esophagus	ESCC	1.38e-03	1.71e-01	0.1251
22858	ICK	P32T-E	Human	Esophagus	ESCC	2.41e-08	1.40e-01	0.1666
22858	ICK	P36T-E	Human	Esophagus	ESCC	3.24e-03	8.50e-02	0.1187
22858	ICK	P37T-E	Human	Esophagus	ESCC	4.03e-09	1.83e-01	0.1371
22858	ICK	P39T-E	Human	Esophagus	ESCC	2.50e-08	2.09e-01	0.0894
22858	ICK	P40T-E	Human	Esophagus	ESCC	4.71e-07	1.78e-01	0.109
22858	ICK	P42T-E	Human	Esophagus	ESCC	3.96e-16	5.80e-01	0.1175
22858	ICK	P44T-E	Human	Esophagus	ESCC	8.33e-05	7.47e-02	0.1096
22858	ICK	P47T-E	Human	Esophagus	ESCC	2.02e-03	8.09e-02	0.1067

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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: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:0072594110	Esophagus	ESCC	establishment of protein localization to organelle	311/8552	422/18723	3.02e-32	2.13e-29	311
GO:004819318	Esophagus	ESCC	Golgi vesicle transport	231/8552	296/18723	1.82e-30	9.63e-28	231
GO:0006913110	Esophagus	ESCC	nucleocytoplasmic transport	230/8552	301/18723	6.04e-28	2.02e-25	230
GO:0051169110	Esophagus	ESCC	nuclear transport	230/8552	301/18723	6.04e-28	2.02e-25	230
GO:0042176111	Esophagus	ESCC	regulation of protein catabolic process	280/8552	391/18723	8.65e-26	2.39e-23	280
GO:0009896111	Esophagus	ESCC	positive regulation of catabolic process	332/8552	492/18723	4.36e-23	9.22e-21	332
GO:0031331111	Esophagus	ESCC	positive regulation of cellular catabolic process	292/8552	427/18723	8.67e-22	1.53e-19	292
GO:003450418	Esophagus	ESCC	protein localization to nucleus	211/8552	290/18723	4.06e-21	6.60e-19	211
GO:1903320111	Esophagus	ESCC	regulation of protein modification by small protein conjugation or removal	181/8552	242/18723	1.80e-20	2.60e-18	181
GO:1903362111	Esophagus	ESCC	regulation of cellular protein catabolic process	188/8552	255/18723	5.12e-20	6.62e-18	188
GO:0045862111	Esophagus	ESCC	positive regulation of proteolysis	256/8552	372/18723	7.88e-20	9.43e-18	256
GO:1903050111	Esophagus	ESCC	regulation of proteolysis involved in cellular protein catabolic process	163/8552	221/18723	1.44e-17	1.27e-15	163
GO:0061136111	Esophagus	ESCC	regulation of proteasomal protein catabolic process	142/8552	187/18723	2.40e-17	2.00e-15	142
GO:0045732111	Esophagus	ESCC	positive regulation of protein catabolic process	167/8552	231/18723	1.47e-16	1.14e-14	167
GO:0031396111	Esophagus	ESCC	regulation of protein ubiquitination	154/8552	210/18723	2.70e-16	2.04e-14	154
GO:0043254111	Esophagus	ESCC	regulation of protein-containing complex assembly	278/8552	428/18723	3.81e-16	2.77e-14	278
GO:0032434111	Esophagus	ESCC	regulation of proteasomal ubiquitin-dependent protein catabolic process	107/8552	134/18723	4.06e-16	2.93e-14	107
GO:2000058111	Esophagus	ESCC	regulation of ubiquitin-dependent protein catabolic process	125/8552	164/18723	1.17e-15	7.76e-14	125

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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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