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: CCDC14

Gene summary for CCDC14

Gene summary.

Gene information	Species	Human
	Gene symbol	CCDC14
	Gene ID	64770
	Gene name	coiled-coil domain containing 14
	Gene Alias	CCDC14
	Cytomap	3q21.1
	Gene Type	protein-coding
	GO ID	GO:0007275
	UniProtAcc	Q49A88

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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
64770	CCDC14	P10T-E	Human	Esophagus	ESCC	1.44e-55	1.00e+00	0.116
64770	CCDC14	P11T-E	Human	Esophagus	ESCC	7.62e-08	5.56e-01	0.1426
64770	CCDC14	P12T-E	Human	Esophagus	ESCC	2.02e-17	2.49e-01	0.1122
64770	CCDC14	P15T-E	Human	Esophagus	ESCC	5.90e-20	4.27e-01	0.1149
64770	CCDC14	P16T-E	Human	Esophagus	ESCC	7.36e-47	8.81e-01	0.1153
64770	CCDC14	P17T-E	Human	Esophagus	ESCC	9.88e-08	3.80e-01	0.1278
64770	CCDC14	P20T-E	Human	Esophagus	ESCC	8.58e-21	3.27e-01	0.1124
64770	CCDC14	P21T-E	Human	Esophagus	ESCC	2.37e-19	4.65e-01	0.1617
64770	CCDC14	P22T-E	Human	Esophagus	ESCC	1.24e-27	5.21e-01	0.1236
64770	CCDC14	P23T-E	Human	Esophagus	ESCC	1.01e-12	3.56e-01	0.108
64770	CCDC14	P24T-E	Human	Esophagus	ESCC	5.62e-08	2.34e-01	0.1287
64770	CCDC14	P26T-E	Human	Esophagus	ESCC	5.00e-23	4.17e-01	0.1276
64770	CCDC14	P27T-E	Human	Esophagus	ESCC	5.56e-27	4.66e-01	0.1055
64770	CCDC14	P28T-E	Human	Esophagus	ESCC	2.12e-26	4.66e-01	0.1149
64770	CCDC14	P30T-E	Human	Esophagus	ESCC	4.47e-10	3.64e-01	0.137
64770	CCDC14	P31T-E	Human	Esophagus	ESCC	6.66e-18	3.74e-01	0.1251
64770	CCDC14	P32T-E	Human	Esophagus	ESCC	1.41e-17	3.35e-01	0.1666
64770	CCDC14	P36T-E	Human	Esophagus	ESCC	8.33e-19	5.41e-01	0.1187
64770	CCDC14	P37T-E	Human	Esophagus	ESCC	5.31e-25	5.28e-01	0.1371
64770	CCDC14	P39T-E	Human	Esophagus	ESCC	2.63e-11	2.48e-01	0.0894

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
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:00309019	Cervix	CC	midbrain development	26/2311	90/18723	2.12e-05	3.82e-04	26
GO:002176210	Cervix	CC	substantia nigra development	16/2311	44/18723	3.81e-05	5.99e-04	16
GO:00488579	Cervix	CC	neural nucleus development	18/2311	64/18723	5.42e-04	5.23e-03	18
GO:0021762	Colorectum	AD	substantia nigra development	21/3918	44/18723	6.60e-05	1.07e-03	21
GO:0048857	Colorectum	AD	neural nucleus development	27/3918	64/18723	9.57e-05	1.45e-03	27
GO:0071539	Colorectum	AD	protein localization to centrosome	16/3918	33/18723	3.86e-04	4.41e-03	16
GO:1905508	Colorectum	AD	protein localization to microtubule organizing center	16/3918	35/18723	8.76e-04	8.51e-03	16
GO:0030901	Colorectum	AD	midbrain development	32/3918	90/18723	9.45e-04	8.95e-03	32
GO:00217621	Colorectum	SER	substantia nigra development	21/2897	44/18723	4.77e-07	2.40e-05	21
GO:00488571	Colorectum	SER	neural nucleus development	26/2897	64/18723	1.09e-06	5.11e-05	26
GO:00309011	Colorectum	SER	midbrain development	29/2897	90/18723	5.50e-05	1.30e-03	29
GO:00217622	Colorectum	MSS	substantia nigra development	21/3467	44/18723	9.54e-06	2.33e-04	21
GO:00488572	Colorectum	MSS	neural nucleus development	26/3467	64/18723	3.19e-05	6.30e-04	26
GO:00715391	Colorectum	MSS	protein localization to centrosome	16/3467	33/18723	8.66e-05	1.40e-03	16
GO:19055081	Colorectum	MSS	protein localization to microtubule organizing center	16/3467	35/18723	2.07e-04	2.89e-03	16
GO:00309012	Colorectum	MSS	midbrain development	31/3467	90/18723	2.36e-04	3.24e-03	31
GO:0044380	Colorectum	MSS	protein localization to cytoskeleton	19/3467	58/18723	6.69e-03	4.38e-02	19
GO:0072698	Colorectum	MSS	protein localization to microtubule cytoskeleton	18/3467	54/18723	6.70e-03	4.38e-02	18
GO:00715392	Colorectum	FAP	protein localization to centrosome	14/2622	33/18723	6.39e-05	1.23e-03	14
GO:19055082	Colorectum	FAP	protein localization to microtubule organizing center	14/2622	35/18723	1.38e-04	2.18e-03	14

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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

CCDC14

SNV

Missense_Mutation

c.1394G>C

p.Arg465Thr

p.R465T

Q49A88

protein_coding

deleterious(0.01)

benign(0.096)

TCGA-A2-A0CL-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

CCDC14

SNV

Missense_Mutation

rs372947520

c.2045N>G

p.Thr682Ser

p.T682S

Q49A88

protein_coding

tolerated(0.53)

benign(0)

TCGA-A8-A08L-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

CCDC14

SNV

Missense_Mutation

c.116N>G

p.Ser39Trp

p.S39W

Q49A88

protein_coding

tolerated_low_confidence(0.2)

benign(0.001)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CCDC14

SNV

Missense_Mutation

novel

c.806N>C

p.Gly269Ala

p.G269A

Q49A88

protein_coding

tolerated(0.24)

benign(0.027)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

CCDC14

SNV

Missense_Mutation

c.679N>T

p.Pro227Ser

p.P227S

Q49A88

protein_coding

tolerated(0.81)

benign(0.046)

TCGA-B6-A0WV-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CCDC14

SNV

Missense_Mutation

c.1682N>C

p.Leu561Pro

p.L561P

Q49A88

protein_coding

deleterious(0)

probably_damaging(0.986)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CCDC14

SNV

Missense_Mutation

c.2129N>T

p.Ser710Phe

p.S710F

Q49A88

protein_coding

tolerated(0.62)

benign(0.146)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

CCDC14

SNV

Missense_Mutation

c.1269N>G

p.Ile423Met

p.I423M

Q49A88

protein_coding

deleterious(0.02)

possibly_damaging(0.882)

TCGA-E9-A1RA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

CCDC14

deletion

Frame_Shift_Del

c.228delA

p.Ala77ArgfsTer4

p.A77Rfs*4

Q49A88

protein_coding

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

CCDC14

insertion

Frame_Shift_Ins

novel

c.1883_1884insGTCTCTCCCTCCTCTAATCCTTCCTATTTACT

p.Leu631ProfsTer12

p.L631Pfs*12

Q49A88

protein_coding

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

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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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