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: OSBPL8

Gene summary for OSBPL8

Gene summary.

Gene information	Species	Human
	Gene symbol	OSBPL8
	Gene ID	114882
	Gene name	oxysterol binding protein like 8
	Gene Alias	MST120
	Cytomap	12q21.2
	Gene Type	protein-coding
	GO ID	GO:0001932
	UniProtAcc	Q5HYM3

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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
114882	OSBPL8	CA_HPV_1	Human	Cervix	CC	1.79e-06	-2.16e-01	0.0264
114882	OSBPL8	CCI_2	Human	Cervix	CC	4.99e-06	6.05e-01	0.5249
114882	OSBPL8	CCII_1	Human	Cervix	CC	1.09e-10	-6.13e-01	0.3249
114882	OSBPL8	Tumor	Human	Cervix	CC	9.77e-19	-5.28e-01	0.1241
114882	OSBPL8	sample1	Human	Cervix	CC	2.03e-03	-4.83e-01	0.0959
114882	OSBPL8	sample3	Human	Cervix	CC	1.24e-14	-4.38e-01	0.1387
114882	OSBPL8	H2	Human	Cervix	HSIL_HPV	1.14e-08	-3.61e-01	0.0632
114882	OSBPL8	L1	Human	Cervix	CC	9.00e-09	-4.87e-01	0.0802
114882	OSBPL8	T1	Human	Cervix	CC	1.19e-11	-5.14e-01	0.0918
114882	OSBPL8	T3	Human	Cervix	CC	4.72e-14	-4.21e-01	0.1389
114882	OSBPL8	LZE4T	Human	Esophagus	ESCC	8.60e-18	5.71e-01	0.0811
114882	OSBPL8	LZE5T	Human	Esophagus	ESCC	5.94e-05	4.97e-01	0.0514
114882	OSBPL8	LZE7T	Human	Esophagus	ESCC	2.61e-06	5.05e-01	0.0667
114882	OSBPL8	LZE8T	Human	Esophagus	ESCC	3.13e-04	-8.14e-03	0.067
114882	OSBPL8	LZE20T	Human	Esophagus	ESCC	1.54e-05	1.61e-01	0.0662
114882	OSBPL8	LZE22D1	Human	Esophagus	HGIN	2.06e-06	7.18e-02	0.0595
114882	OSBPL8	LZE22T	Human	Esophagus	ESCC	3.02e-04	2.21e-01	0.068
114882	OSBPL8	LZE24T	Human	Esophagus	ESCC	4.02e-14	3.84e-01	0.0596
114882	OSBPL8	LZE21T	Human	Esophagus	ESCC	7.15e-08	3.09e-01	0.0655
114882	OSBPL8	LZE6T	Human	Esophagus	ESCC	6.73e-06	1.20e-01	0.0845

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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:003367419	Oral cavity	EOLP	positive regulation of kinase activity	82/2218	467/18723	1.58e-04	1.68e-03	82
GO:00512716	Oral cavity	EOLP	negative regulation of cellular component movement	67/2218	367/18723	1.97e-04	2.00e-03	67
GO:20001466	Oral cavity	EOLP	negative regulation of cell motility	65/2218	359/18723	3.09e-04	2.89e-03	65
GO:00400136	Oral cavity	EOLP	negative regulation of locomotion	67/2218	391/18723	1.17e-03	8.47e-03	67
GO:005189714	Oral cavity	EOLP	positive regulation of protein kinase B signaling	26/2218	120/18723	1.57e-03	1.05e-02	26
GO:004544415	Oral cavity	EOLP	fat cell differentiation	42/2218	229/18723	2.58e-03	1.56e-02	42
GO:00466282	Oral cavity	EOLP	positive regulation of insulin receptor signaling pathway	8/2218	22/18723	2.64e-03	1.59e-02	8
GO:001088811	Oral cavity	EOLP	negative regulation of lipid storage	8/2218	23/18723	3.63e-03	2.04e-02	8
GO:00157483	Oral cavity	EOLP	organophosphate ester transport	28/2218	140/18723	3.66e-03	2.05e-02	28
GO:190007812	Oral cavity	EOLP	positive regulation of cellular response to insulin stimulus	8/2218	25/18723	6.46e-03	3.18e-02	8
GO:005189614	Oral cavity	EOLP	regulation of protein kinase B signaling	33/2218	185/18723	1.05e-02	4.71e-02	33
GO:003450432	Oral cavity	NEOLP	protein localization to nucleus	71/2005	290/18723	1.49e-11	2.21e-09	71
GO:190165331	Oral cavity	NEOLP	cellular response to peptide	78/2005	359/18723	7.21e-10	5.54e-08	78
GO:007137531	Oral cavity	NEOLP	cellular response to peptide hormone stimulus	60/2005	290/18723	3.92e-07	1.19e-05	60
GO:004544422	Oral cavity	NEOLP	fat cell differentiation	50/2005	229/18723	6.79e-07	1.93e-05	50
GO:005127115	Oral cavity	NEOLP	negative regulation of cellular component movement	70/2005	367/18723	1.10e-06	2.90e-05	70
GO:003286931	Oral cavity	NEOLP	cellular response to insulin stimulus	45/2005	203/18723	1.56e-06	3.86e-05	45
GO:004343431	Oral cavity	NEOLP	response to peptide hormone	76/2005	414/18723	1.79e-06	4.33e-05	76
GO:200014615	Oral cavity	NEOLP	negative regulation of cell motility	68/2005	359/18723	2.01e-06	4.77e-05	68
GO:003033614	Oral cavity	NEOLP	negative regulation of cell migration	65/2005	344/18723	3.65e-06	7.97e-05	65

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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

OSBPL8

SNV

Missense_Mutation

c.1103C>A

p.Pro368His

p.P368H

Q9BZF1

protein_coding

tolerated(0.09)

benign(0.416)

TCGA-A7-A0DB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

OSBPL8

SNV

Missense_Mutation

rs201177828

c.1601N>T

p.Gly534Val

p.G534V

Q9BZF1

protein_coding

deleterious(0)

probably_damaging(0.939)

TCGA-A8-A07P-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

5-fluorouracil

OSBPL8

SNV

Missense_Mutation

rs201177828

c.1601G>T

p.Gly534Val

p.G534V

Q9BZF1

protein_coding

deleterious(0)

probably_damaging(0.939)

TCGA-A8-A081-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

OSBPL8

SNV

Missense_Mutation

rs201177828

c.1601N>T

p.Gly534Val

p.G534V

Q9BZF1

protein_coding

deleterious(0)

probably_damaging(0.939)

TCGA-A8-A094-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

OSBPL8

SNV

Missense_Mutation

c.1654N>C

p.Glu552Gln

p.E552Q

Q9BZF1

protein_coding

deleterious(0.01)

benign(0.061)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

OSBPL8

SNV

Missense_Mutation

novel

c.386N>A

p.Arg129Gln

p.R129Q

Q9BZF1

protein_coding

deleterious(0.02)

probably_damaging(0.957)

TCGA-AR-A5QQ-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

carboplatin

OSBPL8

SNV

Missense_Mutation

rs201177828

c.1601G>T

p.Gly534Val

p.G534V

Q9BZF1

protein_coding

deleterious(0)

probably_damaging(0.939)

TCGA-BH-A0BD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

OSBPL8

SNV

Missense_Mutation

c.442G>A

p.Val148Ile

p.V148I

Q9BZF1

protein_coding

tolerated(0.09)

possibly_damaging(0.562)

TCGA-BH-A0BM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

OSBPL8

SNV

Missense_Mutation

novel

c.2608N>C

p.Asp870His

p.D870H

Q9BZF1

protein_coding

tolerated(0.58)

benign(0.001)

TCGA-BH-A2L8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

OSBPL8

SNV

Missense_Mutation

c.602N>A

p.Arg201His

p.R201H

Q9BZF1

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-D8-A1XF-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin+cyclophosphamide

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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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