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: ERP29

Gene summary for ERP29

Gene summary.

Gene information	Species	Human
	Gene symbol	ERP29
	Gene ID	10961
	Gene name	endoplasmic reticulum protein 29
	Gene Alias	C12orf8
	Cytomap	12q24.13
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	P30040

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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
10961	ERP29	CA_HPV_1	Human	Cervix	CC	8.62e-11	6.48e-02	0.0264
10961	ERP29	CA_HPV_3	Human	Cervix	CC	1.02e-02	1.98e-01	0.0414
10961	ERP29	CCI_1	Human	Cervix	CC	5.69e-08	-5.86e-01	0.528
10961	ERP29	CCI_3	Human	Cervix	CC	3.53e-05	-5.36e-01	0.516
10961	ERP29	CCII_1	Human	Cervix	CC	6.01e-19	-7.08e-01	0.3249
10961	ERP29	sample3	Human	Cervix	CC	4.02e-02	5.51e-02	0.1387
10961	ERP29	L1	Human	Cervix	CC	3.21e-11	-4.04e-01	0.0802
10961	ERP29	HTA11_3410_2000001011	Human	Colorectum	AD	8.00e-25	5.45e-01	0.0155
10961	ERP29	HTA11_2487_2000001011	Human	Colorectum	SER	3.45e-21	7.47e-01	-0.1808
10961	ERP29	HTA11_2951_2000001011	Human	Colorectum	AD	3.72e-11	7.48e-01	0.0216
10961	ERP29	HTA11_1938_2000001011	Human	Colorectum	AD	3.08e-18	7.71e-01	-0.0811
10961	ERP29	HTA11_78_2000001011	Human	Colorectum	AD	4.52e-15	5.78e-01	-0.1088
10961	ERP29	HTA11_347_2000001011	Human	Colorectum	AD	6.00e-48	1.04e+00	-0.1954
10961	ERP29	HTA11_411_2000001011	Human	Colorectum	SER	3.33e-07	9.64e-01	-0.2602
10961	ERP29	HTA11_2112_2000001011	Human	Colorectum	SER	2.86e-04	6.92e-01	-0.2196
10961	ERP29	HTA11_3361_2000001011	Human	Colorectum	AD	2.27e-25	9.90e-01	-0.1207
10961	ERP29	HTA11_83_2000001011	Human	Colorectum	SER	5.41e-22	9.20e-01	-0.1526
10961	ERP29	HTA11_696_2000001011	Human	Colorectum	AD	2.20e-45	1.07e+00	-0.1464
10961	ERP29	HTA11_866_2000001011	Human	Colorectum	AD	1.17e-26	7.62e-01	-0.1001
10961	ERP29	HTA11_1391_2000001011	Human	Colorectum	AD	1.17e-35	1.09e+00	-0.059

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
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:009719310	Cervix	CC	intrinsic apoptotic signaling pathway	85/2311	288/18723	4.56e-15	6.46e-12	85
GO:200123310	Cervix	CC	regulation of apoptotic signaling pathway	96/2311	356/18723	4.08e-14	3.05e-11	96
GO:200124210	Cervix	CC	regulation of intrinsic apoptotic signaling pathway	52/2311	164/18723	5.06e-11	1.01e-08	52
GO:003367410	Cervix	CC	positive regulation of kinase activity	101/2311	467/18723	8.66e-09	7.22e-07	101
GO:00458608	Cervix	CC	positive regulation of protein kinase activity	85/2311	386/18723	5.61e-08	3.29e-06	85
GO:190589710	Cervix	CC	regulation of response to endoplasmic reticulum stress	27/2311	82/18723	9.24e-07	3.25e-05	27
GO:00719007	Cervix	CC	regulation of protein serine/threonine kinase activity	75/2311	359/18723	2.76e-06	8.02e-05	75
GO:003497610	Cervix	CC	response to endoplasmic reticulum stress	57/2311	256/18723	5.81e-06	1.42e-04	57
GO:00700599	Cervix	CC	intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	21/2311	63/18723	1.18e-05	2.51e-04	21
GO:00719025	Cervix	CC	positive regulation of protein serine/threonine kinase activity	46/2311	200/18723	1.87e-05	3.47e-04	46
GO:00434104	Cervix	CC	positive regulation of MAPK cascade	90/2311	480/18723	2.92e-05	4.83e-04	90
GO:19022356	Cervix	CC	regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	12/2311	32/18723	2.53e-04	2.79e-03	12
GO:00064579	Cervix	CC	protein folding	44/2311	212/18723	3.43e-04	3.59e-03	44
GO:0097193	Colorectum	AD	intrinsic apoptotic signaling pathway	108/3918	288/18723	6.25e-11	6.41e-09	108
GO:2001242	Colorectum	AD	regulation of intrinsic apoptotic signaling pathway	67/3918	164/18723	4.94e-09	3.16e-07	67
GO:2001233	Colorectum	AD	regulation of apoptotic signaling pathway	119/3918	356/18723	2.14e-08	1.21e-06	119
GO:0034976	Colorectum	AD	response to endoplasmic reticulum stress	90/3918	256/18723	8.48e-08	4.28e-06	90
GO:0006457	Colorectum	AD	protein folding	73/3918	212/18723	3.24e-06	9.10e-05	73
GO:0070059	Colorectum	AD	intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	29/3918	63/18723	7.03e-06	1.73e-04	29
GO:0050708	Colorectum	AD	regulation of protein secretion	83/3918	268/18723	6.59e-05	1.07e-03	83

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0414120	Cervix	CC	Protein processing in endoplasmic reticulum	55/1267	174/8465	1.74e-08	2.68e-07	1.58e-07	55
hsa04141110	Cervix	CC	Protein processing in endoplasmic reticulum	55/1267	174/8465	1.74e-08	2.68e-07	1.58e-07	55
hsa04141	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa041411	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa041412	Colorectum	SER	Protein processing in endoplasmic reticulum	60/1580	174/8465	4.20e-07	7.33e-06	5.32e-06	60
hsa041413	Colorectum	SER	Protein processing in endoplasmic reticulum	60/1580	174/8465	4.20e-07	7.33e-06	5.32e-06	60
hsa041414	Colorectum	MSS	Protein processing in endoplasmic reticulum	75/1875	174/8465	3.78e-10	8.44e-09	5.17e-09	75
hsa041415	Colorectum	MSS	Protein processing in endoplasmic reticulum	75/1875	174/8465	3.78e-10	8.44e-09	5.17e-09	75
hsa041416	Colorectum	MSI-H	Protein processing in endoplasmic reticulum	46/797	174/8465	4.53e-11	9.78e-10	8.19e-10	46
hsa041417	Colorectum	MSI-H	Protein processing in endoplasmic reticulum	46/797	174/8465	4.53e-11	9.78e-10	8.19e-10	46
hsa0414126	Endometrium	AEH	Protein processing in endoplasmic reticulum	62/1197	174/8465	5.97e-13	1.39e-11	1.01e-11	62
hsa04141111	Endometrium	AEH	Protein processing in endoplasmic reticulum	62/1197	174/8465	5.97e-13	1.39e-11	1.01e-11	62
hsa0414127	Endometrium	EEC	Protein processing in endoplasmic reticulum	64/1237	174/8465	2.17e-13	5.09e-12	3.80e-12	64
hsa0414136	Endometrium	EEC	Protein processing in endoplasmic reticulum	64/1237	174/8465	2.17e-13	5.09e-12	3.80e-12	64
hsa0414139	Esophagus	HGIN	Protein processing in endoplasmic reticulum	67/1383	174/8465	1.06e-12	2.16e-11	1.72e-11	67
hsa04141114	Esophagus	HGIN	Protein processing in endoplasmic reticulum	67/1383	174/8465	1.06e-12	2.16e-11	1.72e-11	67
hsa04141211	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa04141310	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa0414114	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114
hsa0414115	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114

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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

ERP29

SNV

Missense_Mutation

rs755173279

c.364N>T

p.Arg122Trp

p.R122W

P30040

protein_coding

tolerated(0.19)

benign(0.003)

TCGA-A8-A06R-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

5-fluorouracil

ERP29

SNV

Missense_Mutation

c.200N>A

p.Gly67Asp

p.G67D

P30040

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-BH-A18U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

ERP29

deletion

Frame_Shift_Del

novel

c.476delC

p.Pro159LeufsTer23

p.P159Lfs*23

P30040

protein_coding

TCGA-A7-A4SA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

ERP29

insertion

In_Frame_Ins

novel

c.277_278insCTAGCT

p.Ile93delinsThrSerPhe

p.I93delinsTSF

P30040

protein_coding

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

ERP29

insertion

Nonsense_Mutation

novel

c.282_283insTACTAATGG

p.Ser94_Asp95insTyrTerTrp

p.S94_D95insY*W

P30040

protein_coding

TCGA-BH-A0HK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

ERP29

SNV

Missense_Mutation

c.699N>A

p.Met233Ile

p.M233I

P30040

protein_coding

tolerated(0.41)

benign(0.003)

TCGA-DR-A0ZL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

ERP29

SNV

Missense_Mutation

rs201620890

c.484N>A

p.Asp162Asn

p.D162N

P30040

protein_coding

deleterious(0.01)

benign(0.394)

TCGA-EA-A3HS-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

ERP29

SNV

Missense_Mutation

c.549N>C

p.Gln183His

p.Q183H

P30040

protein_coding

deleterious(0.02)

benign(0.132)

TCGA-IR-A3LK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

ERP29

SNV

Missense_Mutation

rs146674309

c.358N>T

p.Leu120Phe

p.L120F

P30040

protein_coding

deleterious(0)

possibly_damaging(0.814)

TCGA-D5-6533-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Chemotherapy

oxaliplatin

ERP29

SNV

Missense_Mutation

c.677N>T

p.Arg226Met

p.R226M

P30040

protein_coding

deleterious(0.01)

benign(0.398)

TCGA-AP-A059-01

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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