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: SEC62

Gene summary for SEC62

Gene summary.

Gene information	Species	Human
	Gene symbol	SEC62
	Gene ID	7095
	Gene name	SEC62 homolog, preprotein translocation factor
	Gene Alias	Dtrp1
	Cytomap	3q26.2
	Gene Type	protein-coding
	GO ID	GO:0006605
	UniProtAcc	Q99442

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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
7095	SEC62	GSM4909281	Human	Breast	IDC	1.97e-04	3.36e-01	0.21
7095	SEC62	GSM4909290	Human	Breast	IDC	3.69e-02	3.37e-01	0.2096
7095	SEC62	GSM4909291	Human	Breast	IDC	1.87e-12	5.47e-01	0.1753
7095	SEC62	GSM4909294	Human	Breast	IDC	2.53e-11	-3.34e-01	0.2022
7095	SEC62	GSM4909296	Human	Breast	IDC	3.13e-16	8.53e-02	0.1524
7095	SEC62	GSM4909297	Human	Breast	IDC	1.93e-27	5.23e-02	0.1517
7095	SEC62	GSM4909298	Human	Breast	IDC	8.88e-05	3.59e-01	0.1551
7095	SEC62	GSM4909299	Human	Breast	IDC	1.90e-04	3.21e-01	0.035
7095	SEC62	GSM4909300	Human	Breast	IDC	3.17e-02	3.99e-01	0.0334
7095	SEC62	GSM4909301	Human	Breast	IDC	7.38e-14	3.61e-01	0.1577
7095	SEC62	GSM4909311	Human	Breast	IDC	6.46e-59	9.49e-02	0.1534
7095	SEC62	GSM4909312	Human	Breast	IDC	4.88e-25	3.23e-01	0.1552
7095	SEC62	GSM4909315	Human	Breast	IDC	3.01e-04	9.80e-02	0.21
7095	SEC62	GSM4909319	Human	Breast	IDC	1.38e-71	-1.21e-01	0.1563
7095	SEC62	GSM4909320	Human	Breast	IDC	2.86e-07	-1.17e-01	0.1575
7095	SEC62	GSM4909321	Human	Breast	IDC	1.32e-26	-1.17e-01	0.1559
7095	SEC62	brca2	Human	Breast	Precancer	1.79e-09	3.63e-01	-0.024
7095	SEC62	NCCBC14	Human	Breast	DCIS	2.52e-13	-6.87e-02	0.2021
7095	SEC62	NCCBC2	Human	Breast	DCIS	4.06e-04	-5.06e-01	0.1554
7095	SEC62	NCCBC3	Human	Breast	DCIS	3.62e-05	3.05e-02	0.1198

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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
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
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:00709725	Breast	Precancer	protein localization to endoplasmic reticulum	15/1080	74/18723	1.74e-05	4.17e-04	15
GO:00066059	Breast	Precancer	protein targeting	33/1080	314/18723	6.50e-04	7.99e-03	33
GO:00725948	Breast	Precancer	establishment of protein localization to organelle	41/1080	422/18723	7.75e-04	9.20e-03	41
GO:00718064	Breast	Precancer	protein transmembrane transport	10/1080	59/18723	1.86e-03	1.81e-02	10
GO:00066208	Breast	Precancer	posttranslational protein targeting to endoplasmic reticulum membrane	4/1080	12/18723	3.75e-03	3.04e-02	4
GO:007097213	Breast	IDC	protein localization to endoplasmic reticulum	18/1434	74/18723	8.58e-06	2.47e-04	18
GO:000660514	Breast	IDC	protein targeting	43/1434	314/18723	1.44e-04	2.53e-03	43
GO:007259413	Breast	IDC	establishment of protein localization to organelle	51/1434	422/18723	7.94e-04	9.55e-03	51
GO:007180612	Breast	IDC	protein transmembrane transport	12/1434	59/18723	1.49e-03	1.50e-02	12
GO:007097222	Breast	DCIS	protein localization to endoplasmic reticulum	18/1390	74/18723	5.57e-06	1.60e-04	18
GO:000660523	Breast	DCIS	protein targeting	43/1390	314/18723	7.17e-05	1.41e-03	43
GO:007259423	Breast	DCIS	establishment of protein localization to organelle	51/1390	422/18723	3.91e-04	5.40e-03	51
GO:007180621	Breast	DCIS	protein transmembrane transport	12/1390	59/18723	1.14e-03	1.22e-02	12
GO:0072594	Colorectum	AD	establishment of protein localization to organelle	148/3918	422/18723	7.95e-12	1.04e-09	148
GO:0090150	Colorectum	AD	establishment of protein localization to membrane	100/3918	260/18723	6.01e-11	6.33e-09	100
GO:0006605	Colorectum	AD	protein targeting	105/3918	314/18723	1.39e-07	6.44e-06	105
GO:0070972	Colorectum	AD	protein localization to endoplasmic reticulum	26/3918	74/18723	3.28e-03	2.40e-02	26
GO:0006620	Colorectum	AD	posttranslational protein targeting to endoplasmic reticulum membrane	7/3918	12/18723	5.09e-03	3.38e-02	7
GO:0071806	Colorectum	AD	protein transmembrane transport	21/3918	59/18723	6.58e-03	4.08e-02	21
GO:00725942	Colorectum	MSS	establishment of protein localization to organelle	139/3467	422/18723	5.75e-13	1.12e-10	139

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0414118	Breast	Precancer	Protein processing in endoplasmic reticulum	33/684	174/8465	2.78e-06	3.83e-05	2.94e-05	33
hsa030609	Breast	Precancer	Protein export	6/684	23/8465	8.34e-03	4.54e-02	3.48e-02	6
hsa0414119	Breast	Precancer	Protein processing in endoplasmic reticulum	33/684	174/8465	2.78e-06	3.83e-05	2.94e-05	33
hsa0306012	Breast	Precancer	Protein export	6/684	23/8465	8.34e-03	4.54e-02	3.48e-02	6
hsa0414124	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36
hsa0414134	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36
hsa0414143	Breast	DCIS	Protein processing in endoplasmic reticulum	36/846	174/8465	1.60e-05	1.91e-04	1.41e-04	36
hsa0414153	Breast	DCIS	Protein processing in endoplasmic reticulum	36/846	174/8465	1.60e-05	1.91e-04	1.41e-04	36
hsa04141	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa03060	Colorectum	AD	Protein export	14/2092	23/8465	2.43e-04	1.90e-03	1.21e-03	14
hsa041411	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa030601	Colorectum	AD	Protein export	14/2092	23/8465	2.43e-04	1.90e-03	1.21e-03	14
hsa041414	Colorectum	MSS	Protein processing in endoplasmic reticulum	75/1875	174/8465	3.78e-10	8.44e-09	5.17e-09	75
hsa030602	Colorectum	MSS	Protein export	15/1875	23/8465	1.13e-05	1.26e-04	7.71e-05	15
hsa041415	Colorectum	MSS	Protein processing in endoplasmic reticulum	75/1875	174/8465	3.78e-10	8.44e-09	5.17e-09	75
hsa030603	Colorectum	MSS	Protein export	15/1875	23/8465	1.13e-05	1.26e-04	7.71e-05	15
hsa041418	Colorectum	FAP	Protein processing in endoplasmic reticulum	50/1404	174/8465	3.64e-05	3.68e-04	2.24e-04	50
hsa030606	Colorectum	FAP	Protein export	10/1404	23/8465	2.17e-03	1.05e-02	6.39e-03	10
hsa041419	Colorectum	FAP	Protein processing in endoplasmic reticulum	50/1404	174/8465	3.64e-05	3.68e-04	2.24e-04	50
hsa030607	Colorectum	FAP	Protein export	10/1404	23/8465	2.17e-03	1.05e-02	6.39e-03	10

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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

SEC62

SNV

Missense_Mutation

novel

c.402N>C

p.Lys134Asn

p.K134N

Q99442

protein_coding

tolerated(0.08)

possibly_damaging(0.481)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

SEC62

SNV

Missense_Mutation

rs866931174

c.364N>A

p.Asp122Asn

p.D122N

Q99442

protein_coding

tolerated(0.26)

benign(0.028)

TCGA-AC-A3QQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SEC62

SNV

Missense_Mutation

c.73N>A

p.Ala25Thr

p.A25T

Q99442

protein_coding

deleterious(0)

probably_damaging(0.984)

TCGA-AC-A62V-01

Breast

breast invasive carcinoma

Male

<65

III/IV

Targeted Molecular therapy

denosumab

SEC62

SNV

Missense_Mutation

novel

c.632C>A

p.Thr211Asn

p.T211N

Q99442

protein_coding

deleterious(0.01)

possibly_damaging(0.632)

TCGA-BH-A0BG-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SEC62

SNV

Missense_Mutation

c.7N>A

p.Glu3Lys

p.E3K

Q99442

protein_coding

deleterious(0.01)

benign(0)

TCGA-BH-A18V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SEC62

insertion

In_Frame_Ins

novel

c.953_954insTTTGTGGAGTAAGTGCCTTACAAAGGCAAAAGGGCCTAG

p.Lys318delinsAsnLeuTrpSerLysCysLeuThrLysAlaLysGlyProArg

p.K318delinsNLWSKCLTKAKGPR

Q99442

protein_coding

TCGA-A2-A0EO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

SEC62

insertion

Frame_Shift_Ins

novel

c.362_363insG

p.Asp122ArgfsTer2

p.D122Rfs*2

Q99442

protein_coding

TCGA-AC-A3QQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SEC62

insertion

Frame_Shift_Ins

novel

c.1046_1047insGTATTTGTTAATAAAAAGCTGGGAAAAC

p.Asp350TyrfsTer11

p.D350Yfs*11

Q99442

protein_coding

TCGA-BH-A0H0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

SEC62

SNV

Missense_Mutation

c.7G>A

p.Glu3Lys

p.E3K

Q99442

protein_coding

deleterious(0.01)

benign(0)

TCGA-VS-A9V5-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

SEC62

SNV

Missense_Mutation

novel

c.728N>C

p.Val243Ala

p.V243A

Q99442

protein_coding

deleterious(0.05)

benign(0.262)

TCGA-AZ-4315-01

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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