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: SEC24A

Gene summary for SEC24A

Gene summary.

Gene information	Species	Human
	Gene symbol	SEC24A
	Gene ID	10802
	Gene name	SEC24 homolog A, COPII coat complex component
	Gene Alias	SEC24A
	Cytomap	5q31.1
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	B4E205

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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
10802	SEC24A	LZE4T	Human	Esophagus	ESCC	1.19e-03	1.55e-02	0.0811
10802	SEC24A	LZE7T	Human	Esophagus	ESCC	5.18e-06	1.26e-01	0.0667
10802	SEC24A	LZE8T	Human	Esophagus	ESCC	4.37e-02	7.31e-02	0.067
10802	SEC24A	LZE22T	Human	Esophagus	ESCC	1.23e-02	1.17e-01	0.068
10802	SEC24A	LZE24T	Human	Esophagus	ESCC	1.51e-04	1.00e-01	0.0596
10802	SEC24A	P2T-E	Human	Esophagus	ESCC	9.50e-17	1.00e-01	0.1177
10802	SEC24A	P4T-E	Human	Esophagus	ESCC	6.03e-08	2.11e-01	0.1323
10802	SEC24A	P5T-E	Human	Esophagus	ESCC	1.96e-05	5.71e-02	0.1327
10802	SEC24A	P8T-E	Human	Esophagus	ESCC	8.43e-08	1.39e-01	0.0889
10802	SEC24A	P9T-E	Human	Esophagus	ESCC	4.72e-08	6.38e-02	0.1131
10802	SEC24A	P10T-E	Human	Esophagus	ESCC	1.87e-08	4.86e-02	0.116
10802	SEC24A	P11T-E	Human	Esophagus	ESCC	1.05e-08	3.23e-01	0.1426
10802	SEC24A	P12T-E	Human	Esophagus	ESCC	3.72e-10	1.14e-01	0.1122
10802	SEC24A	P15T-E	Human	Esophagus	ESCC	1.18e-15	1.14e-01	0.1149
10802	SEC24A	P16T-E	Human	Esophagus	ESCC	3.59e-13	2.83e-02	0.1153
10802	SEC24A	P19T-E	Human	Esophagus	ESCC	7.76e-05	3.00e-01	0.1662
10802	SEC24A	P20T-E	Human	Esophagus	ESCC	6.13e-09	4.74e-02	0.1124
10802	SEC24A	P21T-E	Human	Esophagus	ESCC	4.14e-19	1.11e-01	0.1617
10802	SEC24A	P22T-E	Human	Esophagus	ESCC	1.02e-16	1.05e-01	0.1236
10802	SEC24A	P23T-E	Human	Esophagus	ESCC	2.03e-10	2.57e-01	0.108

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:004819318	Esophagus	ESCC	Golgi vesicle transport	231/8552	296/18723	1.82e-30	9.63e-28	231
GO:001605014	Esophagus	ESCC	vesicle organization	211/8552	300/18723	2.85e-18	2.87e-16	211
GO:000688815	Esophagus	ESCC	endoplasmic reticulum to Golgi vesicle-mediated transport	102/8552	130/18723	1.73e-14	9.22e-13	102
GO:0006900111	Esophagus	ESCC	vesicle budding from membrane	54/8552	61/18723	2.66e-12	1.07e-10	54
GO:009011414	Esophagus	ESCC	COPII-coated vesicle budding	27/8552	29/18723	8.09e-08	1.39e-06	27
GO:00901104	Esophagus	ESCC	COPII-coated vesicle cargo loading	14/8552	15/18723	1.47e-04	9.85e-04	14
GO:00354595	Esophagus	ESCC	vesicle cargo loading	19/8552	27/18723	8.35e-03	2.95e-02	19
GO:004819311	Liver	Cirrhotic	Golgi vesicle transport	153/4634	296/18723	1.02e-23	6.43e-21	153
GO:000688811	Liver	Cirrhotic	endoplasmic reticulum to Golgi vesicle-mediated transport	77/4634	130/18723	5.78e-17	7.56e-15	77
GO:001605011	Liver	Cirrhotic	vesicle organization	133/4634	300/18723	7.35e-14	6.41e-12	133
GO:000690012	Liver	Cirrhotic	vesicle budding from membrane	41/4634	61/18723	3.12e-12	2.25e-10	41
GO:009011411	Liver	Cirrhotic	COPII-coated vesicle budding	21/4634	29/18723	8.97e-08	2.63e-06	21
GO:003545911	Liver	Cirrhotic	vesicle cargo loading	15/4634	27/18723	5.96e-04	4.63e-03	15
GO:00901101	Liver	Cirrhotic	COPII-coated vesicle cargo loading	10/4634	15/18723	7.26e-04	5.36e-03	10
GO:004819321	Liver	HCC	Golgi vesicle transport	217/7958	296/18723	2.58e-27	1.02e-24	217
GO:000688821	Liver	HCC	endoplasmic reticulum to Golgi vesicle-mediated transport	100/7958	130/18723	1.15e-15	8.67e-14	100
GO:001605021	Liver	HCC	vesicle organization	194/7958	300/18723	5.58e-15	3.97e-13	194
GO:000690021	Liver	HCC	vesicle budding from membrane	53/7958	61/18723	7.38e-13	3.80e-11	53
GO:00901142	Liver	HCC	COPII-coated vesicle budding	27/7958	29/18723	1.28e-08	3.14e-07	27
GO:00901102	Liver	HCC	COPII-coated vesicle cargo loading	14/7958	15/18723	5.65e-05	5.26e-04	14

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04141211	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa05130211	Esophagus	ESCC	Pathogenic Escherichia coli infection	142/4205	197/8465	8.21e-11	1.06e-09	5.42e-10	142
hsa04141310	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa05130310	Esophagus	ESCC	Pathogenic Escherichia coli infection	142/4205	197/8465	8.21e-11	1.06e-09	5.42e-10	142
hsa0414114	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114
hsa0513022	Liver	Cirrhotic	Pathogenic Escherichia coli infection	88/2530	197/8465	6.48e-06	6.24e-05	3.84e-05	88
hsa0414115	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114
hsa0513032	Liver	Cirrhotic	Pathogenic Escherichia coli infection	88/2530	197/8465	6.48e-06	6.24e-05	3.84e-05	88
hsa0414122	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0513042	Liver	HCC	Pathogenic Escherichia coli infection	129/4020	197/8465	2.02e-07	2.50e-06	1.39e-06	129
hsa0414132	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0513052	Liver	HCC	Pathogenic Escherichia coli infection	129/4020	197/8465	2.02e-07	2.50e-06	1.39e-06	129

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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

SEC24A

SNV

Missense_Mutation

c.112N>A

p.Ala38Thr

p.A38T

O95486

protein_coding

tolerated_low_confidence(1)

benign(0)

TCGA-A2-A1FZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Arimidex

SEC24A

SNV

Missense_Mutation

c.1875N>T

p.Lys625Asn

p.K625N

O95486

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SEC24A

SNV

Missense_Mutation

c.1387N>A

p.Glu463Lys

p.E463K

O95486

protein_coding

deleterious(0.02)

probably_damaging(0.937)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SEC24A

SNV

Missense_Mutation

c.2512N>C

p.Ala838Pro

p.A838P

O95486

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SEC24A

SNV

Missense_Mutation

novel

c.1762N>G

p.Leu588Val

p.L588V

O95486

protein_coding

deleterious(0.01)

probably_damaging(0.916)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SEC24A

SNV

Missense_Mutation

novel

c.1412C>T

p.Thr471Ile

p.T471I

O95486

protein_coding

deleterious(0.01)

possibly_damaging(0.542)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SEC24A

SNV

Missense_Mutation

c.2045N>T

p.Gly682Val

p.G682V

O95486

protein_coding

deleterious(0)

probably_damaging(0.926)

TCGA-AR-A251-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

SEC24A

SNV

Missense_Mutation

c.1928N>T

p.Thr643Ile

p.T643I

O95486

protein_coding

deleterious(0)

benign(0.437)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

SEC24A

insertion

Nonsense_Mutation

novel

c.3001_3002insATTTGTCCGGGCATGGTGGCTTATGCCTGTAATTG

p.Thr1001AsnfsTer11

p.T1001Nfs*11

O95486

protein_coding

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

SEC24A

deletion

Frame_Shift_Del

c.2470delN

p.Cys824ValfsTer4

p.C824Vfs*4

O95486

protein_coding

TCGA-AN-A0AJ-01

Breast

breast invasive 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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