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: SEC14L1

Gene summary for SEC14L1

Gene summary.

Gene information	Species	Human
	Gene symbol	SEC14L1
	Gene ID	6397
	Gene name	SEC14 like lipid binding 1
	Gene Alias	PRELID4A
	Cytomap	17q25.2-q25.3
	Gene Type	protein-coding
	GO ID	GO:0002221
	UniProtAcc	A5PLM6

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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
6397	SEC14L1	S028	Human	Liver	HCC	6.95e-18	8.09e-01	0.2503
6397	SEC14L1	S029	Human	Liver	HCC	6.45e-16	9.49e-01	0.2581
6397	SEC14L1	C04	Human	Oral cavity	OSCC	1.16e-09	5.44e-01	0.2633
6397	SEC14L1	C21	Human	Oral cavity	OSCC	4.06e-19	6.00e-01	0.2678
6397	SEC14L1	C30	Human	Oral cavity	OSCC	3.91e-39	1.51e+00	0.3055
6397	SEC14L1	C38	Human	Oral cavity	OSCC	5.92e-08	7.20e-01	0.172
6397	SEC14L1	C51	Human	Oral cavity	OSCC	7.45e-09	4.91e-01	0.2674
6397	SEC14L1	C57	Human	Oral cavity	OSCC	4.05e-05	2.61e-01	0.1679
6397	SEC14L1	C06	Human	Oral cavity	OSCC	2.00e-02	6.94e-01	0.2699
6397	SEC14L1	C08	Human	Oral cavity	OSCC	2.79e-15	4.53e-01	0.1919
6397	SEC14L1	C09	Human	Oral cavity	OSCC	3.09e-05	2.90e-01	0.1431
6397	SEC14L1	EOLP-1	Human	Oral cavity	EOLP	5.95e-03	1.95e-01	-0.0202
6397	SEC14L1	SYSMH1	Human	Oral cavity	OSCC	8.98e-04	2.24e-01	0.1127
6397	SEC14L1	SYSMH3	Human	Oral cavity	OSCC	1.36e-06	3.44e-01	0.2442
6397	SEC14L1	GSM5252135_BPH511PrPUr_Fcol_3GEX	Human	Prostate	BPH	3.36e-05	3.99e-01	-0.1833
6397	SEC14L1	047563_1562-all-cells	Human	Prostate	BPH	1.33e-05	2.04e-01	0.0791
6397	SEC14L1	048752_1579-all-cells	Human	Prostate	BPH	4.12e-02	2.49e-01	0.1008
6397	SEC14L1	052097_1595-all-cells	Human	Prostate	BPH	3.15e-04	2.33e-01	0.0972
6397	SEC14L1	052099_1652-all-cells	Human	Prostate	BPH	2.59e-04	2.26e-01	0.1038
6397	SEC14L1	Dong_P1	Human	Prostate	Tumor	4.30e-14	1.36e-01	0.035

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:003052210	Endometrium	AEH	intracellular receptor signaling pathway	60/2100	265/18723	7.16e-08	3.77e-06	60
GO:00395293	Endometrium	AEH	RIG-I signaling pathway	11/2100	27/18723	8.09e-05	1.21e-03	11
GO:00395353	Endometrium	AEH	regulation of RIG-I signaling pathway	9/2100	20/18723	1.46e-04	1.94e-03	9
GO:00027535	Endometrium	AEH	cytoplasmic pattern recognition receptor signaling pathway	17/2100	60/18723	2.25e-04	2.75e-03	17
GO:00096159	Endometrium	AEH	response to virus	63/2100	367/18723	3.81e-04	4.10e-03	63
GO:00027645	Endometrium	AEH	immune response-regulating signaling pathway	76/2100	468/18723	5.76e-04	5.71e-03	76
GO:00395312	Endometrium	AEH	regulation of viral-induced cytoplasmic pattern recognition receptor signaling pathway	9/2100	24/18723	7.48e-04	7.12e-03	9
GO:00985864	Endometrium	AEH	cellular response to virus	20/2100	84/18723	8.14e-04	7.66e-03	20
GO:00395282	Endometrium	AEH	cytoplasmic pattern recognition receptor signaling pathway in response to virus	11/2100	34/18723	8.45e-04	7.82e-03	11
GO:00622074	Endometrium	AEH	regulation of pattern recognition receptor signaling pathway	23/2100	105/18723	1.19e-03	1.02e-02	23
GO:00026838	Endometrium	AEH	negative regulation of immune system process	69/2100	434/18723	1.76e-03	1.41e-02	69
GO:00022213	Endometrium	AEH	pattern recognition receptor signaling pathway	31/2100	172/18723	5.16e-03	3.23e-02	31
GO:003052215	Endometrium	EEC	intracellular receptor signaling pathway	65/2168	265/18723	2.52e-09	1.96e-07	65
GO:000275311	Endometrium	EEC	cytoplasmic pattern recognition receptor signaling pathway	20/2168	60/18723	7.27e-06	1.67e-04	20
GO:003952911	Endometrium	EEC	RIG-I signaling pathway	11/2168	27/18723	1.08e-04	1.49e-03	11
GO:000961513	Endometrium	EEC	response to virus	66/2168	367/18723	1.78e-04	2.20e-03	66
GO:003953511	Endometrium	EEC	regulation of RIG-I signaling pathway	9/2168	20/18723	1.87e-04	2.27e-03	9
GO:000276412	Endometrium	EEC	immune response-regulating signaling pathway	80/2168	468/18723	2.20e-04	2.64e-03	80
GO:003953111	Endometrium	EEC	regulation of viral-induced cytoplasmic pattern recognition receptor signaling pathway	9/2168	24/18723	9.45e-04	8.45e-03	9
GO:000268313	Endometrium	EEC	negative regulation of immune system process	72/2168	434/18723	1.04e-03	9.13e-03	72

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

SEC14L1

SNV

Missense_Mutation

c.488N>C

p.Ile163Thr

p.I163T

Q92503

protein_coding

deleterious(0)

probably_damaging(0.982)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SEC14L1

SNV

Missense_Mutation

c.841N>G

p.Leu281Val

p.L281V

Q92503

protein_coding

deleterious(0.02)

possibly_damaging(0.858)

TCGA-C8-A1HM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

SEC14L1

SNV

Missense_Mutation

novel

c.481N>A

p.Glu161Lys

p.E161K

Q92503

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SEC14L1

SNV

Missense_Mutation

novel

c.935N>G

p.Tyr312Cys

p.Y312C

Q92503

protein_coding

tolerated(0.17)

benign(0.018)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SEC14L1

SNV

Missense_Mutation

rs773798440

c.2026N>A

p.Gly676Ser

p.G676S

Q92503

protein_coding

tolerated(0.57)

benign(0.003)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SEC14L1

SNV

Missense_Mutation

rs752687715

c.1528N>A

p.Glu510Lys

p.E510K

Q92503

protein_coding

tolerated(0.07)

possibly_damaging(0.738)

TCGA-EA-A3QE-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SEC14L1

SNV

Missense_Mutation

novel

c.2122N>T

p.His708Tyr

p.H708Y

Q92503

protein_coding

tolerated(1)

benign(0.271)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SEC14L1

SNV

Missense_Mutation

novel

c.135N>G

p.Phe45Leu

p.F45L

Q92503

protein_coding

tolerated(0.63)

benign(0.015)

TCGA-UC-A7PD-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SEC14L1

SNV

Missense_Mutation

rs375335873

c.2098N>A

p.Ala700Thr

p.A700T

Q92503

protein_coding

tolerated(0.24)

benign(0.39)

TCGA-VS-A94Z-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SEC14L1

SNV

Missense_Mutation

novel

c.539N>A

p.Arg180His

p.R180H

Q92503

protein_coding

deleterious(0.03)

probably_damaging(0.923)

TCGA-A6-3810-01

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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