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: CCDC57

Gene summary for CCDC57

Gene summary.

Gene information	Species	Human
	Gene symbol	CCDC57
	Gene ID	284001
	Gene name	coiled-coil domain containing 57
	Gene Alias	CCDC57
	Cytomap	17q25.3
	Gene Type	protein-coding
	GO ID	GO:0000086
	UniProtAcc	Q2TAC2

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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
284001	CCDC57	GSM4909281	Human	Breast	IDC	2.15e-03	-1.81e-01	0.21
284001	CCDC57	GSM4909285	Human	Breast	IDC	1.75e-03	-1.73e-01	0.21
284001	CCDC57	GSM4909286	Human	Breast	IDC	1.33e-03	1.53e-01	0.1081
284001	CCDC57	GSM4909293	Human	Breast	IDC	9.34e-14	4.19e-01	0.1581
284001	CCDC57	GSM4909306	Human	Breast	IDC	7.50e-03	3.27e-01	0.1564
284001	CCDC57	GSM4909308	Human	Breast	IDC	4.46e-02	1.95e-01	0.158
284001	CCDC57	GSM4909311	Human	Breast	IDC	2.73e-10	-1.16e-01	0.1534
284001	CCDC57	GSM4909312	Human	Breast	IDC	6.35e-04	-1.27e-01	0.1552
284001	CCDC57	GSM4909319	Human	Breast	IDC	2.00e-21	1.58e-01	0.1563
284001	CCDC57	brca1	Human	Breast	Precancer	1.06e-03	-1.84e-01	-0.0338
284001	CCDC57	M1	Human	Breast	IDC	6.85e-49	1.12e+00	0.1577
284001	CCDC57	NCCBC14	Human	Breast	DCIS	7.77e-03	-2.19e-02	0.2021
284001	CCDC57	P1	Human	Breast	IDC	4.50e-15	5.17e-01	0.1527
284001	CCDC57	DCIS2	Human	Breast	DCIS	2.00e-52	6.64e-02	0.0085
284001	CCDC57	LZE4T	Human	Esophagus	ESCC	6.86e-07	2.33e-01	0.0811
284001	CCDC57	LZE7T	Human	Esophagus	ESCC	8.24e-06	4.25e-01	0.0667
284001	CCDC57	LZE8T	Human	Esophagus	ESCC	1.21e-05	1.99e-01	0.067
284001	CCDC57	LZE20T	Human	Esophagus	ESCC	3.04e-04	1.20e-01	0.0662
284001	CCDC57	LZE21D1	Human	Esophagus	HGIN	7.88e-04	4.19e-01	0.0632
284001	CCDC57	LZE22D1	Human	Esophagus	HGIN	2.71e-09	2.60e-01	0.0595

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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

∗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:00512589	Breast	IDC	protein polymerization	38/1434	297/18723	1.26e-03	1.34e-02	38
GO:00073465	Breast	IDC	regulation of mitotic cell cycle	51/1434	457/18723	4.30e-03	3.35e-02	51
GO:00459315	Breast	IDC	positive regulation of mitotic cell cycle	18/1434	121/18723	4.90e-03	3.73e-02	18
GO:005125814	Breast	DCIS	protein polymerization	39/1390	297/18723	3.64e-04	5.15e-03	39
GO:000734612	Breast	DCIS	regulation of mitotic cell cycle	52/1390	457/18723	1.38e-03	1.43e-02	52
GO:004593112	Breast	DCIS	positive regulation of mitotic cell cycle	19/1390	121/18723	1.47e-03	1.49e-02	19
GO:00447724	Breast	DCIS	mitotic cell cycle phase transition	46/1390	424/18723	6.16e-03	4.39e-02	46
GO:000734610	Esophagus	HGIN	regulation of mitotic cell cycle	98/2587	457/18723	4.39e-06	1.42e-04	98
GO:00447729	Esophagus	HGIN	mitotic cell cycle phase transition	89/2587	424/18723	2.80e-05	7.21e-04	89
GO:005125826	Esophagus	HGIN	protein polymerization	66/2587	297/18723	4.96e-05	1.19e-03	66
GO:004593110	Esophagus	HGIN	positive regulation of mitotic cell cycle	28/2587	121/18723	3.72e-03	3.39e-02	28
GO:004477216	Esophagus	ESCC	mitotic cell cycle phase transition	281/8552	424/18723	4.63e-18	4.45e-16	281
GO:000734615	Esophagus	ESCC	regulation of mitotic cell cycle	293/8552	457/18723	8.00e-16	5.64e-14	293
GO:004578710	Esophagus	ESCC	positive regulation of cell cycle	196/8552	313/18723	9.27e-10	2.24e-08	196
GO:00448394	Esophagus	ESCC	cell cycle G2/M phase transition	103/8552	148/18723	3.09e-09	6.67e-08	103
GO:00000864	Esophagus	ESCC	G2/M transition of mitotic cell cycle	96/8552	137/18723	6.00e-09	1.23e-07	96
GO:0051258111	Esophagus	ESCC	protein polymerization	183/8552	297/18723	1.94e-08	3.75e-07	183
GO:004593116	Esophagus	ESCC	positive regulation of mitotic cell cycle	83/8552	121/18723	2.78e-07	4.08e-06	83
GO:00070982	Esophagus	ESCC	centrosome cycle	85/8552	130/18723	4.41e-06	4.69e-05	85
GO:00310233	Esophagus	ESCC	microtubule organizing center organization	92/8552	143/18723	5.04e-06	5.31e-05	92

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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

CCDC57

SNV

Missense_Mutation

novel

c.678N>C

p.Glu226Asp

p.E226D

Q2TAC2

protein_coding

deleterious(0.03)

possibly_damaging(0.809)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

CCDC57

SNV

Missense_Mutation

novel

c.454N>G

p.Leu152Val

p.L152V

Q2TAC2

protein_coding

tolerated(0.07)

possibly_damaging(0.519)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

CCDC57

SNV

Missense_Mutation

rs531085389

c.1595N>A

p.Arg532Gln

p.R532Q

Q2TAC2

protein_coding

deleterious(0.02)

probably_damaging(0.996)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CCDC57

SNV

Missense_Mutation

rs755409077

c.1600N>A

p.Ala534Thr

p.A534T

Q2TAC2

protein_coding

tolerated(0.1)

benign(0.007)

TCGA-AR-A251-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

CCDC57

SNV

Missense_Mutation

c.254N>T

p.Glu85Val

p.E85V

Q2TAC2

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-BH-A18S-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CCDC57

SNV

Missense_Mutation

c.1754A>T

p.Glu585Val

p.E585V

Q2TAC2

protein_coding

deleterious(0)

possibly_damaging(0.776)

TCGA-E9-A1RB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

methotrexate

CCDC57

insertion

In_Frame_Ins

novel

c.1381_1382insAACTCCCGACCTCAGGTGATCTGCCCACCTCGGCCT

p.Ala461delinsGluLeuProThrSerGlyAspLeuProThrSerAlaSer

p.A461delinsELPTSGDLPTSAS

Q2TAC2

protein_coding

TCGA-A2-A04Y-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

CCDC57

deletion

Frame_Shift_Del

novel

c.845delA

p.Lys282ArgfsTer21

p.K282Rfs*21

Q2TAC2

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

CCDC57

SNV

Missense_Mutation

rs866591635

c.1024N>A

p.Ala342Thr

p.A342T

Q2TAC2

protein_coding

tolerated(0.35)

benign(0.021)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CCDC57

SNV

Missense_Mutation

novel

c.319C>G

p.Ile107Met

p.I107M

protein_coding

deleterious_low_confidence(0.01)

benign(0.02)

TCGA-EK-A3GN-01

Cervix

cervical & endocervical cancer

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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