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: SEC24D

Gene summary for SEC24D

Gene summary.

Gene information	Species	Human
	Gene symbol	SEC24D
	Gene ID	9871
	Gene name	SEC24 homolog D, COPII coat complex component
	Gene Alias	CLCRP2
	Cytomap	4q26
	Gene Type	protein-coding
	GO ID	GO:0001701
	UniProtAcc	O94855

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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
9871	SEC24D	LZE4T	Human	Esophagus	ESCC	1.63e-07	1.36e-01	0.0811
9871	SEC24D	LZE7T	Human	Esophagus	ESCC	2.44e-07	2.65e-01	0.0667
9871	SEC24D	LZE21D1	Human	Esophagus	HGIN	1.99e-02	2.11e-01	0.0632
9871	SEC24D	LZE24T	Human	Esophagus	ESCC	8.58e-07	1.26e-01	0.0596
9871	SEC24D	P1T-E	Human	Esophagus	ESCC	2.98e-02	5.93e-02	0.0875
9871	SEC24D	P2T-E	Human	Esophagus	ESCC	5.29e-12	2.64e-01	0.1177
9871	SEC24D	P4T-E	Human	Esophagus	ESCC	6.74e-16	3.57e-01	0.1323
9871	SEC24D	P8T-E	Human	Esophagus	ESCC	1.86e-15	2.27e-01	0.0889
9871	SEC24D	P9T-E	Human	Esophagus	ESCC	4.82e-08	2.22e-01	0.1131
9871	SEC24D	P10T-E	Human	Esophagus	ESCC	1.28e-06	9.62e-02	0.116
9871	SEC24D	P11T-E	Human	Esophagus	ESCC	4.51e-05	3.03e-01	0.1426
9871	SEC24D	P12T-E	Human	Esophagus	ESCC	1.06e-17	2.75e-01	0.1122
9871	SEC24D	P16T-E	Human	Esophagus	ESCC	2.42e-08	1.59e-01	0.1153
9871	SEC24D	P17T-E	Human	Esophagus	ESCC	9.39e-04	2.72e-01	0.1278
9871	SEC24D	P21T-E	Human	Esophagus	ESCC	1.47e-10	2.06e-01	0.1617
9871	SEC24D	P22T-E	Human	Esophagus	ESCC	7.63e-03	1.28e-01	0.1236
9871	SEC24D	P23T-E	Human	Esophagus	ESCC	2.68e-07	4.28e-01	0.108
9871	SEC24D	P24T-E	Human	Esophagus	ESCC	7.54e-09	2.31e-01	0.1287
9871	SEC24D	P26T-E	Human	Esophagus	ESCC	2.00e-36	6.91e-01	0.1276
9871	SEC24D	P27T-E	Human	Esophagus	ESCC	4.59e-16	1.95e-01	0.1055

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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
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
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:004819317	Esophagus	HGIN	Golgi vesicle transport	83/2587	296/18723	8.59e-11	8.89e-09	83
GO:00068889	Esophagus	HGIN	endoplasmic reticulum to Golgi vesicle-mediated transport	40/2587	130/18723	4.67e-07	2.07e-05	40
GO:000690020	Esophagus	HGIN	vesicle budding from membrane	23/2587	61/18723	2.85e-06	9.93e-05	23
GO:000170118	Esophagus	HGIN	in utero embryonic development	77/2587	367/18723	9.56e-05	2.05e-03	77
GO:00160509	Esophagus	HGIN	vesicle organization	65/2587	300/18723	1.24e-04	2.54e-03	65
GO:00901146	Esophagus	HGIN	COPII-coated vesicle budding	11/2587	29/18723	1.08e-03	1.32e-02	11
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:000170119	Esophagus	ESCC	in utero embryonic development	243/8552	367/18723	1.00e-15	6.86e-14	243
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:00481936	Liver	NAFLD	Golgi vesicle transport	66/1882	296/18723	3.66e-10	9.30e-08	66
GO:00069007	Liver	NAFLD	vesicle budding from membrane	17/1882	61/18723	7.31e-05	1.52e-03	17
GO:00354593	Liver	NAFLD	vesicle cargo loading	10/1882	27/18723	1.74e-04	3.08e-03	10
GO:00160505	Liver	NAFLD	vesicle organization	50/1882	300/18723	2.42e-04	4.06e-03	50
GO:0090110	Liver	NAFLD	COPII-coated vesicle cargo loading	7/1882	15/18723	3.18e-04	4.95e-03	7
GO:00901143	Liver	NAFLD	COPII-coated vesicle budding	10/1882	29/18723	3.42e-04	5.22e-03	10

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0414139	Esophagus	HGIN	Protein processing in endoplasmic reticulum	67/1383	174/8465	1.06e-12	2.16e-11	1.72e-11	67
hsa0513039	Esophagus	HGIN	Pathogenic Escherichia coli infection	54/1383	197/8465	4.91e-05	6.15e-04	4.89e-04	54
hsa04141114	Esophagus	HGIN	Protein processing in endoplasmic reticulum	67/1383	174/8465	1.06e-12	2.16e-11	1.72e-11	67
hsa05130115	Esophagus	HGIN	Pathogenic Escherichia coli infection	54/1383	197/8465	4.91e-05	6.15e-04	4.89e-04	54
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
hsa0513014	Liver	NAFLD	Pathogenic Escherichia coli infection	45/1043	197/8465	2.31e-05	6.88e-04	5.54e-04	45
hsa0513015	Liver	NAFLD	Pathogenic Escherichia coli infection	45/1043	197/8465	2.31e-05	6.88e-04	5.54e-04	45
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
hsa0513016	Lung	IAC	Pathogenic Escherichia coli infection	45/1053	197/8465	2.93e-05	6.14e-04	4.08e-04	45
hsa0414116	Lung	IAC	Protein processing in endoplasmic reticulum	37/1053	174/8465	6.53e-04	5.73e-03	3.81e-03	37
hsa0513017	Lung	IAC	Pathogenic Escherichia coli infection	45/1053	197/8465	2.93e-05	6.14e-04	4.08e-04	45
hsa0414117	Lung	IAC	Protein processing in endoplasmic reticulum	37/1053	174/8465	6.53e-04	5.73e-03	3.81e-03	37
hsa0513023	Lung	AIS	Pathogenic Escherichia coli infection	42/961	197/8465	3.43e-05	5.62e-04	3.59e-04	42
hsa0414123	Lung	AIS	Protein processing in endoplasmic reticulum	35/961	174/8465	4.88e-04	4.39e-03	2.81e-03	35

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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

SEC24D

SNV

Missense_Mutation

c.2642N>T

p.Ser881Phe

p.S881F

O94855

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-A2-A0CX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SEC24D

SNV

Missense_Mutation

novel

c.130N>A

p.Pro44Thr

p.P44T

O94855

protein_coding

tolerated_low_confidence(0.12)

benign(0.007)

TCGA-AC-A8OR-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SEC24D

SNV

Missense_Mutation

rs151309585

c.2143G>A

p.Asp715Asn

p.D715N

O94855

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SEC24D

SNV

Missense_Mutation

novel

c.1472N>G

p.Asn491Ser

p.N491S

O94855

protein_coding

tolerated(0.17)

benign(0.25)

TCGA-AN-A0AJ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SEC24D

SNV

Missense_Mutation

c.1163N>C

p.Cys388Ser

p.C388S

O94855

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AR-A0TP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

SEC24D

SNV

Missense_Mutation

novel

c.2881N>A

p.Glu961Lys

p.E961K

O94855

protein_coding

tolerated(0.78)

benign(0.218)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SEC24D

SNV

Missense_Mutation

c.168N>A

p.Met56Ile

p.M56I

O94855

protein_coding

tolerated_low_confidence(0.39)

benign(0)

TCGA-BH-A0HA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SEC24D

SNV

Missense_Mutation

c.2203N>A

p.Asp735Asn

p.D735N

O94855

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

SEC24D

SNV

Missense_Mutation

c.1011N>G

p.Ile337Met

p.I337M

O94855

protein_coding

deleterious(0)

possibly_damaging(0.579)

TCGA-BH-A1EY-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SEC24D

deletion

Frame_Shift_Del

novel

c.2932delN

p.Gln978AsnfsTer8

p.Q978Nfs*8

O94855

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

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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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