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: IFT57

Gene summary for IFT57

Gene summary.

Gene information	Species	Human
	Gene symbol	IFT57
	Gene ID	55081
	Gene name	intraflagellar transport 57
	Gene Alias	ESRRBL1
	Cytomap	3q13.12-q13.13
	Gene Type	protein-coding
	GO ID	GO:0001838
	UniProtAcc	Q9NWB7

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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
55081	IFT57	LZE4T	Human	Esophagus	ESCC	1.03e-16	3.80e-01	0.0811
55081	IFT57	LZE7T	Human	Esophagus	ESCC	4.40e-09	6.64e-01	0.0667
55081	IFT57	LZE8T	Human	Esophagus	ESCC	6.28e-16	5.48e-01	0.067
55081	IFT57	LZE20T	Human	Esophagus	ESCC	1.30e-06	1.23e-01	0.0662
55081	IFT57	LZE22D1	Human	Esophagus	HGIN	4.62e-03	2.37e-02	0.0595
55081	IFT57	LZE24T	Human	Esophagus	ESCC	9.89e-17	7.18e-01	0.0596
55081	IFT57	LZE6T	Human	Esophagus	ESCC	5.60e-04	1.38e-01	0.0845
55081	IFT57	P1T-E	Human	Esophagus	ESCC	9.02e-13	4.56e-01	0.0875
55081	IFT57	P2T-E	Human	Esophagus	ESCC	4.14e-43	8.21e-01	0.1177
55081	IFT57	P4T-E	Human	Esophagus	ESCC	3.13e-20	4.22e-01	0.1323
55081	IFT57	P5T-E	Human	Esophagus	ESCC	8.23e-37	8.53e-01	0.1327
55081	IFT57	P8T-E	Human	Esophagus	ESCC	5.83e-53	1.10e+00	0.0889
55081	IFT57	P9T-E	Human	Esophagus	ESCC	4.35e-23	4.64e-01	0.1131
55081	IFT57	P10T-E	Human	Esophagus	ESCC	1.17e-41	8.67e-01	0.116
55081	IFT57	P11T-E	Human	Esophagus	ESCC	4.16e-24	7.80e-01	0.1426
55081	IFT57	P12T-E	Human	Esophagus	ESCC	2.29e-10	3.77e-01	0.1122
55081	IFT57	P15T-E	Human	Esophagus	ESCC	1.44e-27	5.75e-01	0.1149
55081	IFT57	P16T-E	Human	Esophagus	ESCC	2.50e-47	1.06e+00	0.1153
55081	IFT57	P17T-E	Human	Esophagus	ESCC	4.90e-08	4.27e-01	0.1278
55081	IFT57	P19T-E	Human	Esophagus	ESCC	1.21e-11	9.18e-01	0.1662

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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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
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:001095227	Skin	cSCC	positive regulation of peptidase activity	85/4864	197/18723	1.14e-07	2.69e-06	85
GO:004328128	Skin	cSCC	regulation of cysteine-type endopeptidase activity involved in apoptotic process	89/4864	209/18723	1.20e-07	2.79e-06	89
GO:200011628	Skin	cSCC	regulation of cysteine-type endopeptidase activity	97/4864	235/18723	2.01e-07	4.34e-06	97
GO:0010950112	Skin	cSCC	positive regulation of endopeptidase activity	74/4864	179/18723	4.98e-06	7.25e-05	74
GO:003070524	Skin	cSCC	cytoskeleton-dependent intracellular transport	77/4864	195/18723	2.32e-05	2.67e-04	77
GO:005067324	Skin	cSCC	epithelial cell proliferation	144/4864	437/18723	6.07e-04	4.38e-03	144
GO:001402015	Skin	cSCC	primary neural tube formation	39/4864	94/18723	7.37e-04	5.15e-03	39
GO:000184315	Skin	cSCC	neural tube closure	37/4864	88/18723	7.39e-04	5.15e-03	37
GO:006060615	Skin	cSCC	tube closure	37/4864	89/18723	9.52e-04	6.47e-03	37
GO:0043280111	Skin	cSCC	positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	50/4864	129/18723	9.55e-04	6.47e-03	50
GO:001097014	Skin	cSCC	transport along microtubule	58/4864	155/18723	1.09e-03	7.24e-03	58
GO:000184117	Skin	cSCC	neural tube formation	41/4864	102/18723	1.16e-03	7.61e-03	41
GO:000183822	Skin	cSCC	embryonic epithelial tube formation	47/4864	121/18723	1.26e-03	8.18e-03	47
GO:001633113	Skin	cSCC	morphogenesis of embryonic epithelium	55/4864	147/18723	1.45e-03	9.11e-03	55
GO:200105624	Skin	cSCC	positive regulation of cysteine-type endopeptidase activity	55/4864	148/18723	1.73e-03	1.06e-02	55
GO:003514822	Skin	cSCC	tube formation	54/4864	148/18723	3.00e-03	1.66e-02	54
GO:007217521	Skin	cSCC	epithelial tube formation	49/4864	132/18723	3.06e-03	1.68e-02	49
GO:0045862113	Thyroid	PTC	positive regulation of proteolysis	198/5968	372/18723	6.68e-18	6.91e-16	198
GO:0030705111	Thyroid	PTC	cytoskeleton-dependent intracellular transport	104/5968	195/18723	3.87e-10	1.24e-08	104
GO:00315037	Thyroid	PTC	protein-containing complex localization	107/5968	220/18723	1.47e-07	2.82e-06	107

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0501630	Esophagus	HGIN	Huntington disease	129/1383	306/8465	6.81e-28	7.41e-26	5.88e-26	129
hsa0502230	Esophagus	HGIN	Pathways of neurodegeneration - multiple diseases	153/1383	476/8465	1.22e-18	4.41e-17	3.50e-17	153
hsa05016113	Esophagus	HGIN	Huntington disease	129/1383	306/8465	6.81e-28	7.41e-26	5.88e-26	129
hsa05022113	Esophagus	HGIN	Pathways of neurodegeneration - multiple diseases	153/1383	476/8465	1.22e-18	4.41e-17	3.50e-17	153
hsa05016210	Esophagus	ESCC	Huntington disease	226/4205	306/8465	1.38e-18	8.72e-17	4.46e-17	226
hsa05022210	Esophagus	ESCC	Pathways of neurodegeneration - multiple diseases	318/4205	476/8465	6.10e-15	2.04e-13	1.05e-13	318
hsa0501638	Esophagus	ESCC	Huntington disease	226/4205	306/8465	1.38e-18	8.72e-17	4.46e-17	226
hsa0502238	Esophagus	ESCC	Pathways of neurodegeneration - multiple diseases	318/4205	476/8465	6.10e-15	2.04e-13	1.05e-13	318
hsa0501614	Liver	Cirrhotic	Huntington disease	172/2530	306/8465	1.65e-22	1.10e-20	6.77e-21	172
hsa0502214	Liver	Cirrhotic	Pathways of neurodegeneration - multiple diseases	217/2530	476/8465	7.30e-14	2.03e-12	1.25e-12	217
hsa0501615	Liver	Cirrhotic	Huntington disease	172/2530	306/8465	1.65e-22	1.10e-20	6.77e-21	172
hsa0502215	Liver	Cirrhotic	Pathways of neurodegeneration - multiple diseases	217/2530	476/8465	7.30e-14	2.03e-12	1.25e-12	217
hsa0501622	Liver	HCC	Huntington disease	219/4020	306/8465	3.06e-18	3.42e-16	1.90e-16	219
hsa0502222	Liver	HCC	Pathways of neurodegeneration - multiple diseases	298/4020	476/8465	6.59e-12	1.30e-10	7.22e-11	298
hsa0501632	Liver	HCC	Huntington disease	219/4020	306/8465	3.06e-18	3.42e-16	1.90e-16	219
hsa0502232	Liver	HCC	Pathways of neurodegeneration - multiple diseases	298/4020	476/8465	6.59e-12	1.30e-10	7.22e-11	298
hsa0501628	Oral cavity	OSCC	Huntington disease	204/3704	306/8465	1.70e-16	7.13e-15	3.63e-15	204
hsa0502228	Oral cavity	OSCC	Pathways of neurodegeneration - multiple diseases	292/3704	476/8465	1.60e-15	4.47e-14	2.28e-14	292
hsa05016112	Oral cavity	OSCC	Huntington disease	204/3704	306/8465	1.70e-16	7.13e-15	3.63e-15	204
hsa05022112	Oral cavity	OSCC	Pathways of neurodegeneration - multiple diseases	292/3704	476/8465	1.60e-15	4.47e-14	2.28e-14	292

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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

IFT57

SNV

Missense_Mutation

c.634A>G

p.Lys212Glu

p.K212E

Q9NWB7

protein_coding

tolerated(0.13)

benign(0.207)

TCGA-E2-A1LA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

IFT57

SNV

Missense_Mutation

c.79N>A

p.Glu27Lys

p.E27K

Q9NWB7

protein_coding

tolerated_low_confidence(0.21)

benign(0)

TCGA-EK-A2PG-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

IFT57

SNV

Missense_Mutation

c.544N>A

p.Asp182Asn

p.D182N

Q9NWB7

protein_coding

deleterious(0.02)

benign(0.281)

TCGA-EK-A2R7-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

IFT57

SNV

Missense_Mutation

novel

c.22N>C

p.Val8Leu

p.V8L

Q9NWB7

protein_coding

deleterious_low_confidence(0.05)

benign(0.022)

TCGA-EK-A3GK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

IFT57

SNV

Missense_Mutation

c.380N>T

p.Arg127Ile

p.R127I

Q9NWB7

protein_coding

tolerated(0.41)

benign(0.013)

TCGA-AA-3510-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

IFT57

SNV

Missense_Mutation

rs548451697

c.244N>A

p.Glu82Lys

p.E82K

Q9NWB7

protein_coding

deleterious(0.03)

probably_damaging(0.94)

TCGA-AZ-4315-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

IFT57

SNV

Missense_Mutation

rs371129548

c.733N>T

p.Arg245Cys

p.R245C

Q9NWB7

protein_coding

deleterious(0)

probably_damaging(0.942)

TCGA-CM-6162-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Chemotherapy

oxaliplatin

IFT57

insertion

Frame_Shift_Ins

novel

c.1137_1138insAGTATGTT

p.Leu380SerfsTer4

p.L380Sfs*4

Q9NWB7

protein_coding

TCGA-AM-5820-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

IFT57

insertion

Nonsense_Mutation

novel

c.874_875insGAAATCATTCTT

p.Glu292delinsGlyAsnHisSerTer

p.E292delinsGNHS*

Q9NWB7

protein_coding

TCGA-AM-5820-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

IFT57

SNV

Missense_Mutation

novel

c.1262N>G

p.Ile421Ser

p.I421S

Q9NWB7

protein_coding

deleterious_low_confidence(0)

benign(0.054)

TCGA-A5-A0G1-01

Endometrium

uterine corpus endometrioid carcinoma

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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