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: PNPLA8

Gene summary for PNPLA8

Gene summary.

Gene information	Species	Human
	Gene symbol	PNPLA8
	Gene ID	50640
	Gene name	patatin like phospholipase domain containing 8
	Gene Alias	IPLA2-2
	Cytomap	7q31.1
	Gene Type	protein-coding
	GO ID	GO:0001516
	UniProtAcc	A0A024R746

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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
50640	PNPLA8	LZE2D	Human	Esophagus	HGIN	2.75e-02	2.86e-01	0.0642
50640	PNPLA8	LZE4T	Human	Esophagus	ESCC	2.84e-11	3.87e-01	0.0811
50640	PNPLA8	LZE7T	Human	Esophagus	ESCC	2.89e-11	3.55e-01	0.0667
50640	PNPLA8	LZE8T	Human	Esophagus	ESCC	3.68e-07	2.92e-01	0.067
50640	PNPLA8	LZE20T	Human	Esophagus	ESCC	2.69e-05	8.14e-02	0.0662
50640	PNPLA8	LZE22T	Human	Esophagus	ESCC	8.76e-06	1.65e-01	0.068
50640	PNPLA8	LZE24T	Human	Esophagus	ESCC	3.66e-18	5.01e-01	0.0596
50640	PNPLA8	LZE21T	Human	Esophagus	ESCC	4.25e-05	1.78e-01	0.0655
50640	PNPLA8	LZE6T	Human	Esophagus	ESCC	6.53e-05	2.40e-01	0.0845
50640	PNPLA8	P1T-E	Human	Esophagus	ESCC	2.34e-04	4.60e-01	0.0875
50640	PNPLA8	P2T-E	Human	Esophagus	ESCC	2.59e-12	1.29e-01	0.1177
50640	PNPLA8	P4T-E	Human	Esophagus	ESCC	8.76e-18	4.08e-01	0.1323
50640	PNPLA8	P5T-E	Human	Esophagus	ESCC	1.53e-08	1.56e-01	0.1327
50640	PNPLA8	P8T-E	Human	Esophagus	ESCC	1.10e-18	4.53e-01	0.0889
50640	PNPLA8	P9T-E	Human	Esophagus	ESCC	9.65e-17	4.19e-01	0.1131
50640	PNPLA8	P10T-E	Human	Esophagus	ESCC	3.96e-19	4.02e-01	0.116
50640	PNPLA8	P11T-E	Human	Esophagus	ESCC	1.39e-18	9.19e-01	0.1426
50640	PNPLA8	P12T-E	Human	Esophagus	ESCC	1.97e-21	5.32e-01	0.1122
50640	PNPLA8	P15T-E	Human	Esophagus	ESCC	9.71e-24	6.81e-01	0.1149
50640	PNPLA8	P16T-E	Human	Esophagus	ESCC	9.50e-16	3.79e-01	0.1153

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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
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:00465032	Liver	NAFLD	glycerolipid catabolic process	14/1882	65/18723	4.57e-03	3.68e-02	14
GO:00066906	Liver	NAFLD	icosanoid metabolic process	22/1882	123/18723	5.33e-03	4.11e-02	22
GO:000697912	Liver	Cirrhotic	response to oxidative stress	196/4634	446/18723	2.80e-19	5.86e-17	196
GO:000663112	Liver	Cirrhotic	fatty acid metabolic process	165/4634	390/18723	1.29e-14	1.26e-12	165
GO:006219712	Liver	Cirrhotic	cellular response to chemical stress	147/4634	337/18723	1.84e-14	1.72e-12	147
GO:001605312	Liver	Cirrhotic	organic acid biosynthetic process	139/4634	316/18723	4.28e-14	3.83e-12	139
GO:004639412	Liver	Cirrhotic	carboxylic acid biosynthetic process	137/4634	314/18723	1.40e-13	1.14e-11	137
GO:003459912	Liver	Cirrhotic	cellular response to oxidative stress	127/4634	288/18723	4.29e-13	3.32e-11	127
GO:007233011	Liver	Cirrhotic	monocarboxylic acid biosynthetic process	93/4634	214/18723	1.43e-09	6.16e-08	93
GO:005508811	Liver	Cirrhotic	lipid homeostasis	74/4634	167/18723	2.46e-08	8.51e-07	74
GO:000663311	Liver	Cirrhotic	fatty acid biosynthetic process	70/4634	163/18723	2.57e-07	6.41e-06	70
GO:004424212	Liver	Cirrhotic	cellular lipid catabolic process	82/4634	214/18723	6.91e-06	1.08e-04	82
GO:001604212	Liver	Cirrhotic	lipid catabolic process	112/4634	320/18723	2.31e-05	3.03e-04	112
GO:001087611	Liver	Cirrhotic	lipid localization	147/4634	448/18723	6.24e-05	7.12e-04	147
GO:000686911	Liver	Cirrhotic	lipid transport	128/4634	398/18723	4.54e-04	3.69e-03	128
GO:19004077	Liver	Cirrhotic	regulation of cellular response to oxidative stress	36/4634	89/18723	7.79e-04	5.73e-03	36
GO:00066926	Liver	Cirrhotic	prostanoid metabolic process	22/4634	49/18723	1.64e-03	1.05e-02	22
GO:00066936	Liver	Cirrhotic	prostaglandin metabolic process	22/4634	49/18723	1.64e-03	1.05e-02	22
GO:003355911	Liver	Cirrhotic	unsaturated fatty acid metabolic process	43/4634	116/18723	2.09e-03	1.29e-02	43
GO:19028827	Liver	Cirrhotic	regulation of response to oxidative stress	36/4634	98/18723	5.44e-03	2.77e-02	36

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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

PNPLA8

SNV

Missense_Mutation

novel

c.1333C>A

p.Leu445Ile

p.L445I

Q9NP80

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PNPLA8

SNV

Missense_Mutation

novel

c.1663A>G

p.Arg555Gly

p.R555G

Q9NP80

protein_coding

deleterious(0.01)

benign(0.422)

TCGA-AR-A256-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

PNPLA8

SNV

Missense_Mutation

c.757N>G

p.Ile253Val

p.I253V

Q9NP80

protein_coding

tolerated(0.75)

benign(0)

TCGA-EW-A1P6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

PNPLA8

insertion

Frame_Shift_Ins

novel

c.1980_1981insAATTTCATTTTGCAATGCCTTGTGGAGGTAGGAGGCGACAA

p.Gly661AsnfsTer21

p.G661Nfs*21

Q9NP80

protein_coding

TCGA-A2-A04P-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxol

PNPLA8

insertion

Frame_Shift_Ins

novel

c.596_597insCT

p.Lys199AsnfsTer44

p.K199Nfs*44

Q9NP80

protein_coding

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

PNPLA8

insertion

Frame_Shift_Ins

novel

c.595_596insG

p.Lys199ArgfsTer14

p.K199Rfs*14

Q9NP80

protein_coding

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

PNPLA8

insertion

Nonsense_Mutation

novel

c.445_446insCACAAGACTATTTGGACTAA

p.Asn149ThrfsTer7

p.N149Tfs*7

Q9NP80

protein_coding

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PNPLA8

insertion

Nonsense_Mutation

novel

c.634_635insGAAAGAATGAATAAGACTTACTATTTGATGGCAAAATAGAGT

p.Asn212delinsArgLysAsnGluTerAspLeuLeuPheAspGlyLysIleGluTyr

p.N212delinsRKNE*DLLFDGKIEY

Q9NP80

protein_coding

TCGA-AR-A251-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

PNPLA8

SNV

Missense_Mutation

rs557023667

c.1385G>A

p.Arg462Gln

p.R462Q

Q9NP80

protein_coding

tolerated(0.12)

benign(0.164)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PNPLA8

SNV

Missense_Mutation

novel

c.1501G>A

p.Glu501Lys

p.E501K

Q9NP80

protein_coding

deleterious(0)

possibly_damaging(0.744)

TCGA-MA-AA41-01

Cervix

cervical & endocervical cancer

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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