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: CPNE1

Gene summary for CPNE1

Gene summary.

Gene information	Species	Human
	Gene symbol	CPNE1
	Gene ID	8904
	Gene name	copine 1
	Gene Alias	COPN1
	Cytomap	20q11.22
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	B0QZ18

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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
8904	CPNE1	HTA11_3410_2000001011	Human	Colorectum	AD	1.85e-03	2.36e-01	0.0155
8904	CPNE1	HTA11_347_2000001011	Human	Colorectum	AD	4.32e-05	2.96e-01	-0.1954
8904	CPNE1	HTA11_1391_2000001011	Human	Colorectum	AD	1.81e-10	5.20e-01	-0.059
8904	CPNE1	HTA11_866_3004761011	Human	Colorectum	AD	3.05e-20	6.97e-01	0.096
8904	CPNE1	HTA11_7696_3000711011	Human	Colorectum	AD	3.97e-04	3.13e-01	0.0674
8904	CPNE1	HTA11_6818_2000001021	Human	Colorectum	AD	4.84e-05	3.90e-01	0.0588
8904	CPNE1	HTA11_99999970781_79442	Human	Colorectum	MSS	2.76e-06	3.60e-01	0.294
8904	CPNE1	HTA11_99999971662_82457	Human	Colorectum	MSS	1.71e-34	1.07e+00	0.3859
8904	CPNE1	HTA11_99999973899_84307	Human	Colorectum	MSS	4.12e-18	1.06e+00	0.2585
8904	CPNE1	HTA11_99999974143_84620	Human	Colorectum	MSS	1.63e-41	1.10e+00	0.3005
8904	CPNE1	CRC-3-11773	Human	Colorectum	CRC	3.65e-08	5.63e-01	0.2564
8904	CPNE1	LZE4T	Human	Esophagus	ESCC	3.18e-16	7.18e-01	0.0811
8904	CPNE1	LZE7T	Human	Esophagus	ESCC	7.66e-05	6.22e-01	0.0667
8904	CPNE1	LZE8T	Human	Esophagus	ESCC	2.12e-14	5.68e-01	0.067
8904	CPNE1	LZE20T	Human	Esophagus	ESCC	6.47e-05	4.30e-01	0.0662
8904	CPNE1	LZE24T	Human	Esophagus	ESCC	1.52e-44	1.89e+00	0.0596
8904	CPNE1	LZE21T	Human	Esophagus	ESCC	2.60e-03	4.14e-02	0.0655
8904	CPNE1	LZE6T	Human	Esophagus	ESCC	4.46e-10	9.36e-01	0.0845
8904	CPNE1	P1T-E	Human	Esophagus	ESCC	4.00e-08	6.63e-01	0.0875
8904	CPNE1	P2T-E	Human	Esophagus	ESCC	8.23e-60	1.13e+00	0.1177

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:007135620	Esophagus	ESCC	cellular response to tumor necrosis factor	132/8552	229/18723	1.69e-04	1.11e-03	132
GO:00433924	Esophagus	ESCC	negative regulation of DNA binding	37/8552	52/18723	1.75e-04	1.14e-03	37
GO:00019615	Esophagus	ESCC	positive regulation of cytokine-mediated signaling pathway	35/8552	50/18723	4.33e-04	2.44e-03	35
GO:00607605	Esophagus	ESCC	positive regulation of response to cytokine stimulus	39/8552	57/18723	4.34e-04	2.44e-03	39
GO:006056010	Esophagus	ESCC	developmental growth involved in morphogenesis	131/8552	234/18723	9.28e-04	4.73e-03	131
GO:007124117	Esophagus	ESCC	cellular response to inorganic substance	125/8552	226/18723	2.17e-03	9.67e-03	125
GO:00108033	Esophagus	ESCC	regulation of tumor necrosis factor-mediated signaling pathway	31/8552	47/18723	4.01e-03	1.62e-02	31
GO:00380615	Esophagus	ESCC	NIK/NF-kappaB signaling	81/8552	143/18723	5.33e-03	2.00e-02	81
GO:004858810	Esophagus	ESCC	developmental cell growth	125/8552	234/18723	1.01e-02	3.46e-02	125
GO:005109812	Liver	Cirrhotic	regulation of binding	148/4634	363/18723	9.14e-12	5.97e-10	148
GO:001003812	Liver	Cirrhotic	response to metal ion	150/4634	373/18723	2.27e-11	1.37e-09	150
GO:00072494	Liver	Cirrhotic	I-kappaB kinase/NF-kappaB signaling	108/4634	281/18723	2.21e-07	5.64e-06	108
GO:00431225	Liver	Cirrhotic	regulation of I-kappaB kinase/NF-kappaB signaling	95/4634	249/18723	1.68e-06	3.22e-05	95
GO:005159211	Liver	Cirrhotic	response to calcium ion	61/4634	149/18723	9.47e-06	1.38e-04	61
GO:001604911	Liver	Cirrhotic	cell growth	160/4634	482/18723	1.50e-05	2.07e-04	160
GO:00511006	Liver	Cirrhotic	negative regulation of binding	63/4634	162/18723	4.54e-05	5.31e-04	63
GO:00712487	Liver	Cirrhotic	cellular response to metal ion	73/4634	197/18723	7.73e-05	8.54e-04	73
GO:1901222	Liver	Cirrhotic	regulation of NIK/NF-kappaB signaling	46/4634	112/18723	1.03e-04	1.06e-03	46
GO:00712417	Liver	Cirrhotic	cellular response to inorganic substance	81/4634	226/18723	1.21e-04	1.20e-03	81
GO:00346126	Liver	Cirrhotic	response to tumor necrosis factor	89/4634	253/18723	1.24e-04	1.22e-03	89

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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

CPNE1

SNV

Missense_Mutation

c.1263N>A

p.Met421Ile

p.M421I

protein_coding

tolerated(0.7)

benign(0)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

CPNE1

SNV

Missense_Mutation

c.820N>C

p.Glu274Gln

p.E274Q

protein_coding

tolerated(0.27)

benign(0.007)

TCGA-D8-A147-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine

CPNE1

SNV

Missense_Mutation

c.1000G>A

p.Asp334Asn

p.D334N

protein_coding

deleterious(0.03)

probably_damaging(0.995)

TCGA-E9-A243-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

CPNE1

SNV

Missense_Mutation

novel

c.833N>A

p.Ser278Tyr

p.S278Y

protein_coding

deleterious(0)

probably_damaging(0.929)

TCGA-LL-A440-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

CPNE1

insertion

Frame_Shift_Ins

novel

c.811_812insTGAGACAGAGTCTGGCCCTCTCACCCAGGCTGGAGTGTGGTGGCGTG

p.Cys271LeufsTer19

p.C271Lfs*19

protein_coding

TCGA-A1-A0SQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

CPNE1

insertion

In_Frame_Ins

novel

c.967_968insGTGCGG

p.Met323delinsSerAlaVal

p.M323delinsSAV

protein_coding

TCGA-AN-A03X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CPNE1

insertion

Nonsense_Mutation

novel

c.965_966insTTTTTGAGAAAGAGTCTTGCTCTGTCACCCAGGCTG

p.Leu322_Met323insPheTerGluArgValLeuLeuCysHisProGlyTrp

p.L322_M323insF*ERVLLCHPGW

protein_coding

TCGA-AN-A03X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CPNE1

SNV

Missense_Mutation

novel

c.1086N>C

p.Leu362Phe

p.L362F

protein_coding

deleterious(0)

possibly_damaging(0.714)

TCGA-DG-A2KM-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CPNE1

SNV

Missense_Mutation

c.550G>A

p.Glu184Lys

p.E184K

protein_coding

deleterious(0)

probably_damaging(0.98)

TCGA-MU-A5YI-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

CPNE1

SNV

Missense_Mutation

c.841N>C

p.Asp281His

p.D281H

protein_coding

deleterious(0)

probably_damaging(0.973)

TCGA-AA-3494-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

folinic

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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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