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: SEC23A

Gene summary for SEC23A

Gene summary.

Gene information	Species	Human
	Gene symbol	SEC23A
	Gene ID	10484
	Gene name	SEC23 homolog A, COPII coat complex component
	Gene Alias	CLSD
	Cytomap	14q21.1
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	Q15436

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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
10484	SEC23A	HTA11_3410_2000001011	Human	Colorectum	AD	5.59e-05	-4.78e-01	0.0155
10484	SEC23A	HTA11_7696_3000711011	Human	Colorectum	AD	1.01e-07	-3.90e-01	0.0674
10484	SEC23A	HTA11_99999970781_79442	Human	Colorectum	MSS	1.41e-02	-2.61e-01	0.294
10484	SEC23A	HTA11_99999971662_82457	Human	Colorectum	MSS	1.08e-08	-4.11e-01	0.3859
10484	SEC23A	HTA11_99999974143_84620	Human	Colorectum	MSS	2.54e-17	-5.04e-01	0.3005
10484	SEC23A	A002-C-010	Human	Colorectum	FAP	5.80e-04	-2.03e-01	0.242
10484	SEC23A	A015-C-203	Human	Colorectum	FAP	1.12e-22	-4.13e-01	-0.1294
10484	SEC23A	A015-C-204	Human	Colorectum	FAP	4.07e-02	-2.50e-01	-0.0228
10484	SEC23A	A014-C-040	Human	Colorectum	FAP	6.01e-05	-6.35e-01	-0.1184
10484	SEC23A	A002-C-201	Human	Colorectum	FAP	1.56e-09	-4.41e-01	0.0324
10484	SEC23A	A002-C-203	Human	Colorectum	FAP	2.10e-02	-2.16e-01	0.2786
10484	SEC23A	A001-C-119	Human	Colorectum	FAP	4.92e-04	-4.87e-01	-0.1557
10484	SEC23A	A001-C-108	Human	Colorectum	FAP	5.13e-15	-3.86e-01	-0.0272
10484	SEC23A	A002-C-205	Human	Colorectum	FAP	5.14e-16	-4.53e-01	-0.1236
10484	SEC23A	A001-C-104	Human	Colorectum	FAP	5.45e-03	-2.58e-01	0.0184
10484	SEC23A	A015-C-005	Human	Colorectum	FAP	8.56e-04	-3.48e-01	-0.0336
10484	SEC23A	A015-C-006	Human	Colorectum	FAP	3.78e-12	-5.92e-01	-0.0994
10484	SEC23A	A015-C-106	Human	Colorectum	FAP	1.19e-12	-3.31e-01	-0.0511
10484	SEC23A	A002-C-114	Human	Colorectum	FAP	4.58e-14	-5.26e-01	-0.1561
10484	SEC23A	A015-C-104	Human	Colorectum	FAP	1.15e-26	-4.01e-01	-0.1899

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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
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
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:0072659	Colorectum	AD	protein localization to plasma membrane	122/3918	284/18723	2.86e-17	1.49e-14	122
GO:1990778	Colorectum	AD	protein localization to cell periphery	129/3918	333/18723	5.51e-14	1.15e-11	129
GO:0048193	Colorectum	AD	Golgi vesicle transport	109/3918	296/18723	1.80e-10	1.68e-08	109
GO:0006900	Colorectum	AD	vesicle budding from membrane	32/3918	61/18723	5.38e-08	2.81e-06	32
GO:0016050	Colorectum	AD	vesicle organization	101/3918	300/18723	1.65e-07	7.17e-06	101
GO:0006888	Colorectum	AD	endoplasmic reticulum to Golgi vesicle-mediated transport	44/3918	130/18723	4.13e-04	4.68e-03	44
GO:00726592	Colorectum	MSS	protein localization to plasma membrane	113/3467	284/18723	3.23e-17	1.55e-14	113
GO:19907782	Colorectum	MSS	protein localization to cell periphery	120/3467	333/18723	2.02e-14	5.47e-12	120
GO:00481932	Colorectum	MSS	Golgi vesicle transport	101/3467	296/18723	9.09e-11	9.77e-09	101
GO:00069002	Colorectum	MSS	vesicle budding from membrane	31/3467	61/18723	1.17e-08	7.06e-07	31
GO:00160502	Colorectum	MSS	vesicle organization	93/3467	300/18723	1.04e-07	4.97e-06	93
GO:00068882	Colorectum	MSS	endoplasmic reticulum to Golgi vesicle-mediated transport	44/3467	130/18723	2.17e-05	4.60e-04	44
GO:0090114	Colorectum	MSS	COPII-coated vesicle budding	12/3467	29/18723	3.60e-03	2.66e-02	12
GO:0035459	Colorectum	MSS	vesicle cargo loading	11/3467	27/18723	6.03e-03	4.04e-02	11
GO:00726594	Colorectum	FAP	protein localization to plasma membrane	95/2622	284/18723	4.86e-17	9.93e-14	95
GO:19907784	Colorectum	FAP	protein localization to cell periphery	100/2622	333/18723	2.19e-14	2.68e-11	100
GO:00481934	Colorectum	FAP	Golgi vesicle transport	77/2622	296/18723	2.86e-08	2.62e-06	77
GO:00069004	Colorectum	FAP	vesicle budding from membrane	26/2622	61/18723	4.65e-08	3.86e-06	26
GO:00160503	Colorectum	FAP	vesicle organization	74/2622	300/18723	5.16e-07	2.66e-05	74
GO:00901141	Colorectum	FAP	COPII-coated vesicle budding	11/2622	29/18723	1.20e-03	1.14e-02	11

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
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
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
hsa041418	Colorectum	FAP	Protein processing in endoplasmic reticulum	50/1404	174/8465	3.64e-05	3.68e-04	2.24e-04	50
hsa041419	Colorectum	FAP	Protein processing in endoplasmic reticulum	50/1404	174/8465	3.64e-05	3.68e-04	2.24e-04	50
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
hsa0414122	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0414132	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0414116	Lung	IAC	Protein processing in endoplasmic reticulum	37/1053	174/8465	6.53e-04	5.73e-03	3.81e-03	37
hsa0414117	Lung	IAC	Protein processing in endoplasmic reticulum	37/1053	174/8465	6.53e-04	5.73e-03	3.81e-03	37
hsa0414123	Lung	AIS	Protein processing in endoplasmic reticulum	35/961	174/8465	4.88e-04	4.39e-03	2.81e-03	35
hsa0414133	Lung	AIS	Protein processing in endoplasmic reticulum	35/961	174/8465	4.88e-04	4.39e-03	2.81e-03	35
hsa0414130	Oral cavity	OSCC	Protein processing in endoplasmic reticulum	143/3704	174/8465	6.82e-26	2.28e-23	1.16e-23	143
hsa04141113	Oral cavity	OSCC	Protein processing in endoplasmic reticulum	143/3704	174/8465	6.82e-26	2.28e-23	1.16e-23	143
hsa0414145	Oral cavity	EOLP	Protein processing in endoplasmic reticulum	70/1218	174/8465	2.84e-17	3.06e-15	1.81e-15	70
hsa0414155	Oral cavity	EOLP	Protein processing in endoplasmic reticulum	70/1218	174/8465	2.84e-17	3.06e-15	1.81e-15	70

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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

SEC23A

SNV

Missense_Mutation

c.1330N>A

p.Cys444Ser

p.C444S

Q15436

protein_coding

tolerated(1)

benign(0.001)

TCGA-AN-A0FV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SEC23A

SNV

Missense_Mutation

novel

c.2071G>A

p.Asp691Asn

p.D691N

Q15436

protein_coding

deleterious(0.01)

probably_damaging(0.965)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SEC23A

SNV

Missense_Mutation

c.893C>T

p.Pro298Leu

p.P298L

Q15436

protein_coding

deleterious(0.02)

possibly_damaging(0.782)

TCGA-C8-A12T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SEC23A

SNV

Missense_Mutation

c.1690G>A

p.Asp564Asn

p.D564N

Q15436

protein_coding

deleterious(0.04)

benign(0.06)

TCGA-GM-A2DB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

SEC23A

insertion

Frame_Shift_Ins

novel

c.640_641insAT

p.Ala214AspfsTer24

p.A214Dfs*24

Q15436

protein_coding

TCGA-BH-A0AY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

SEC23A

insertion

Nonsense_Mutation

novel

c.638_639insTCCCAGCACTTTGGGAGGCTGAGGTGGGC

p.Gln213HisfsTer8

p.Q213Hfs*8

Q15436

protein_coding

TCGA-BH-A0AY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

SEC23A

SNV

Missense_Mutation

rs756632254

c.197N>A

p.Cys66Tyr

p.C66Y

Q15436

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SEC23A

SNV

Missense_Mutation

rs572679988

c.1478G>A

p.Arg493His

p.R493H

Q15436

protein_coding

tolerated(0.09)

possibly_damaging(0.531)

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SEC23A

SNV

Missense_Mutation

c.344C>G

p.Ser115Cys

p.S115C

Q15436

protein_coding

deleterious(0.02)

possibly_damaging(0.827)

TCGA-EK-A2PL-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

SEC23A

SNV

Missense_Mutation

c.1828C>G

p.Gln610Glu

p.Q610E

Q15436

protein_coding

tolerated(1)

benign(0.001)

TCGA-FU-A40J-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

carboplatin

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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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