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: CNPPD1

Gene summary for CNPPD1

Gene summary.

Gene information	Species	Human
	Gene symbol	CNPPD1
	Gene ID	27013
	Gene name	cyclin Pas1/PHO80 domain containing 1
	Gene Alias	C2orf24
	Cytomap	2q35
	Gene Type	protein-coding
	GO ID	GO:0000079
	UniProtAcc	A0A024R432

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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
27013	CNPPD1	S014	Human	Liver	HCC	3.17e-25	9.25e-01	0.2254
27013	CNPPD1	S015	Human	Liver	HCC	8.80e-29	1.34e+00	0.2375
27013	CNPPD1	S016	Human	Liver	HCC	1.74e-29	1.09e+00	0.2243
27013	CNPPD1	S027	Human	Liver	HCC	1.08e-08	9.99e-01	0.2446
27013	CNPPD1	S028	Human	Liver	HCC	5.19e-21	9.37e-01	0.2503
27013	CNPPD1	S029	Human	Liver	HCC	1.47e-27	1.11e+00	0.2581
27013	CNPPD1	C04	Human	Oral cavity	OSCC	3.87e-09	5.76e-01	0.2633
27013	CNPPD1	C21	Human	Oral cavity	OSCC	9.78e-28	9.11e-01	0.2678
27013	CNPPD1	C30	Human	Oral cavity	OSCC	4.40e-23	1.02e+00	0.3055
27013	CNPPD1	C38	Human	Oral cavity	OSCC	1.31e-03	6.64e-01	0.172
27013	CNPPD1	C43	Human	Oral cavity	OSCC	9.74e-17	4.05e-01	0.1704
27013	CNPPD1	C46	Human	Oral cavity	OSCC	5.39e-17	4.44e-01	0.1673
27013	CNPPD1	C51	Human	Oral cavity	OSCC	2.13e-04	3.06e-01	0.2674
27013	CNPPD1	C57	Human	Oral cavity	OSCC	5.42e-11	4.20e-01	0.1679
27013	CNPPD1	C06	Human	Oral cavity	OSCC	2.59e-05	8.70e-01	0.2699
27013	CNPPD1	C07	Human	Oral cavity	OSCC	2.10e-04	8.66e-01	0.2491
27013	CNPPD1	C08	Human	Oral cavity	OSCC	1.52e-12	3.27e-01	0.1919
27013	CNPPD1	C09	Human	Oral cavity	OSCC	5.18e-07	2.57e-01	0.1431
27013	CNPPD1	LN22	Human	Oral cavity	OSCC	4.61e-02	5.22e-01	0.1733
27013	CNPPD1	LN46	Human	Oral cavity	OSCC	2.35e-09	3.88e-01	0.1666

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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:0071900	Colorectum	AD	regulation of protein serine/threonine kinase activity	98/3918	359/18723	2.18e-03	1.73e-02	98
GO:00719001	Colorectum	SER	regulation of protein serine/threonine kinase activity	74/2897	359/18723	5.22e-03	3.96e-02	74
GO:00719002	Colorectum	MSS	regulation of protein serine/threonine kinase activity	93/3467	359/18723	2.98e-04	3.91e-03	93
GO:007190016	Esophagus	ESCC	regulation of protein serine/threonine kinase activity	227/8552	359/18723	1.12e-11	4.10e-10	227
GO:19040294	Esophagus	ESCC	regulation of cyclin-dependent protein kinase activity	69/8552	98/18723	6.04e-07	7.91e-06	69
GO:00000794	Esophagus	ESCC	regulation of cyclin-dependent protein serine/threonine kinase activity	66/8552	94/18723	1.24e-06	1.53e-05	66
GO:007190011	Liver	Cirrhotic	regulation of protein serine/threonine kinase activity	110/4634	359/18723	6.19e-03	3.08e-02	110
GO:007190021	Liver	HCC	regulation of protein serine/threonine kinase activity	189/7958	359/18723	5.97e-05	5.47e-04	189
GO:0000079	Liver	HCC	regulation of cyclin-dependent protein serine/threonine kinase activity	55/7958	94/18723	1.25e-03	6.91e-03	55
GO:1904029	Liver	HCC	regulation of cyclin-dependent protein kinase activity	57/7958	98/18723	1.26e-03	6.92e-03	57
GO:007190010	Oral cavity	OSCC	regulation of protein serine/threonine kinase activity	201/7305	359/18723	3.90e-11	1.27e-09	201
GO:19040293	Oral cavity	OSCC	regulation of cyclin-dependent protein kinase activity	60/7305	98/18723	6.90e-06	7.56e-05	60
GO:00000793	Oral cavity	OSCC	regulation of cyclin-dependent protein serine/threonine kinase activity	58/7305	94/18723	6.92e-06	7.57e-05	58
GO:007190015	Oral cavity	LP	regulation of protein serine/threonine kinase activity	119/4623	359/18723	1.70e-04	1.90e-03	119
GO:000007911	Oral cavity	LP	regulation of cyclin-dependent protein serine/threonine kinase activity	34/4623	94/18723	8.52e-03	4.61e-02	34
GO:00000795	Skin	cSCC	regulation of cyclin-dependent protein serine/threonine kinase activity	41/4864	94/18723	1.53e-04	1.35e-03	41
GO:190402911	Skin	cSCC	regulation of cyclin-dependent protein kinase activity	42/4864	98/18723	2.05e-04	1.70e-03	42
GO:007190024	Skin	cSCC	regulation of protein serine/threonine kinase activity	123/4864	359/18723	2.70e-04	2.17e-03	123
GO:0071900110	Thyroid	PTC	regulation of protein serine/threonine kinase activity	164/5968	359/18723	2.41e-08	5.43e-07	164
GO:190402912	Thyroid	PTC	regulation of cyclin-dependent protein kinase activity	49/5968	98/18723	1.40e-04	1.09e-03	49

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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

CNPPD1

SNV

Missense_Mutation

c.842N>A

p.Cys281Tyr

p.C281Y

Q9BV87

protein_coding

tolerated(0.35)

benign(0.188)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CNPPD1

SNV

Missense_Mutation

novel

c.436N>A

p.Asp146Asn

p.D146N

Q9BV87

protein_coding

tolerated(0.05)

probably_damaging(0.984)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CNPPD1

SNV

Missense_Mutation

rs770379185

c.599N>A

p.Arg200Gln

p.R200Q

Q9BV87

protein_coding

deleterious(0)

probably_damaging(0.965)

TCGA-C8-A274-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

CNPPD1

SNV

Missense_Mutation

rs374803866

c.227N>A

p.Arg76Gln

p.R76Q

Q9BV87

protein_coding

deleterious(0.01)

possibly_damaging(0.472)

TCGA-E2-A56Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

CNPPD1

insertion

Frame_Shift_Ins

novel

c.481_482insATACACCCAGTTCGGCCTC

p.Ala161AspfsTer23

p.A161Dfs*23

Q9BV87

protein_coding

TCGA-A8-A06P-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unspecific

CNPPD1

insertion

Frame_Shift_Ins

novel

c.479_480insG

p.Asn160LysfsTer18

p.N160Kfs*18

Q9BV87

protein_coding

TCGA-A8-A06P-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unspecific

CNPPD1

SNV

Missense_Mutation

novel

c.992N>G

p.Thr331Ser

p.T331S

Q9BV87

protein_coding

tolerated_low_confidence(0.79)

benign(0)

TCGA-5M-AAT5-01

Colorectum

colon adenocarcinoma

Unknown

I/II

Unknown

CNPPD1

SNV

Missense_Mutation

c.781N>C

p.Cys261Arg

p.C261R

Q9BV87

protein_coding

tolerated(0.6)

benign(0.083)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

CNPPD1

SNV

Missense_Mutation

c.953N>T

p.Pro318Leu

p.P318L

Q9BV87

protein_coding

tolerated_low_confidence(0.63)

possibly_damaging(0.648)

TCGA-AA-A02H-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

CNPPD1

SNV

Missense_Mutation

c.619N>T

p.Asp207Tyr

p.D207Y

Q9BV87

protein_coding

deleterious(0)

probably_damaging(0.972)

TCGA-AZ-6601-01

Colorectum

colon adenocarcinoma

Male

>=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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