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: PIWIL2

Gene summary for PIWIL2

Gene summary.

Gene information	Species	Human
	Gene symbol	PIWIL2
	Gene ID	55124
	Gene name	piwi like RNA-mediated gene silencing 2
	Gene Alias	CT80
	Cytomap	8p21.3
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q8TC59

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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
55124	PIWIL2	HCC1	Human	Liver	HCC	8.50e-11	1.46e+00	0.5336
55124	PIWIL2	HCC2	Human	Liver	HCC	7.26e-17	1.31e+00	0.5341
55124	PIWIL2	HCC5	Human	Liver	HCC	6.19e-13	2.25e+00	0.4932

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
Liver		NAFLD: Non-alcoholic fatty liver disease

∗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:00346601	Liver	HCC	ncRNA metabolic process	332/7958	485/18723	1.48e-31	7.80e-29	332
GO:000641722	Liver	HCC	regulation of translation	287/7958	468/18723	8.79e-17	8.08e-15	287
GO:001657021	Liver	HCC	histone modification	283/7958	463/18723	2.68e-16	2.33e-14	283
GO:00182052	Liver	HCC	peptidyl-lysine modification	230/7958	376/18723	1.51e-13	8.32e-12	230
GO:00064732	Liver	HCC	protein acetylation	135/7958	201/18723	1.20e-12	5.92e-11	135
GO:00435432	Liver	HCC	protein acylation	157/7958	243/18723	2.40e-12	1.12e-10	157
GO:00183942	Liver	HCC	peptidyl-lysine acetylation	116/7958	169/18723	5.11e-12	2.23e-10	116
GO:004572712	Liver	HCC	positive regulation of translation	97/7958	136/18723	8.51e-12	3.55e-10	97
GO:003425022	Liver	HCC	positive regulation of cellular amide metabolic process	110/7958	162/18723	5.14e-11	1.92e-09	110
GO:00064752	Liver	HCC	internal protein amino acid acetylation	107/7958	160/18723	3.77e-10	1.23e-08	107
GO:00183932	Liver	HCC	internal peptidyl-lysine acetylation	105/7958	158/18723	9.48e-10	2.90e-08	105
GO:00165732	Liver	HCC	histone acetylation	101/7958	152/18723	1.99e-09	5.63e-08	101
GO:00905011	Liver	HCC	RNA phosphodiester bond hydrolysis	101/7958	152/18723	1.99e-09	5.63e-08	101
GO:003105621	Liver	HCC	regulation of histone modification	99/7958	152/18723	1.40e-08	3.40e-07	99
GO:00434141	Liver	HCC	macromolecule methylation	183/7958	316/18723	2.00e-08	4.72e-07	183
GO:0032259	Liver	HCC	methylation	206/7958	364/18723	3.35e-08	7.53e-07	206
GO:0090305	Liver	HCC	nucleic acid phosphodiester bond hydrolysis	152/7958	261/18723	1.90e-07	3.46e-06	152
GO:004578711	Liver	HCC	positive regulation of cell cycle	172/7958	313/18723	5.29e-06	6.58e-05	172
GO:0048285	Liver	HCC	organelle fission	254/7958	488/18723	1.07e-05	1.23e-04	254
GO:0000966	Liver	HCC	RNA 5'-end processing	20/7958	23/18723	1.37e-05	1.51e-04	20

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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

PIWIL2

SNV

Missense_Mutation

c.2197N>A

p.Asp733Asn

p.D733N

Q8TC59

protein_coding

tolerated(0.3)

benign(0.161)

TCGA-BH-A0AV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

PIWIL2

SNV

Missense_Mutation

rs546657162

c.1903N>T

p.Arg635Cys

p.R635C

Q8TC59

protein_coding

deleterious(0)

possibly_damaging(0.462)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

PIWIL2

SNV

Missense_Mutation

c.160C>T

p.Pro54Ser

p.P54S

Q8TC59

protein_coding

tolerated_low_confidence(0.19)

benign(0.001)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PIWIL2

SNV

Missense_Mutation

c.64G>A

p.Val22Ile

p.V22I

Q8TC59

protein_coding

tolerated_low_confidence(0.13)

benign(0.005)

TCGA-BH-A18L-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

PIWIL2

SNV

Missense_Mutation

novel

c.1403N>C

p.Asp468Ala

p.D468A

Q8TC59

protein_coding

deleterious(0.01)

benign(0.039)

TCGA-C8-A12X-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PIWIL2

SNV

Missense_Mutation

c.2543N>C

p.Val848Ala

p.V848A

Q8TC59

protein_coding

tolerated(0.39)

benign(0.012)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

PIWIL2

SNV

Missense_Mutation

novel

c.1403N>C

p.Asp468Ala

p.D468A

Q8TC59

protein_coding

deleterious(0.01)

benign(0.039)

TCGA-E9-A1RG-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

tamoxiphen

PIWIL2

deletion

Frame_Shift_Del

novel

c.2225_2240delTCGGGATGGATGTTTA

p.Ile742ThrfsTer42

p.I742Tfs*42

Q8TC59

protein_coding

TCGA-A8-A085-01

Breast

breast invasive carcinoma

Male

<65

I/II

Hormone Therapy

tamoxiphen

PIWIL2

insertion

Nonsense_Mutation

novel

c.969_970insTGAACCGTGGAGGCGGAGGTTGCGGTGAGCTGAG

p.Asn324Ter

p.N324*

Q8TC59

protein_coding

TCGA-A8-A09M-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

paclitaxel

PIWIL2

insertion

In_Frame_Ins

novel

c.711_712insCTGTGGGTTTGGTCTCCATGTTCC

p.Asn237_Glu238insLeuTrpValTrpSerProCysSer

p.N237_E238insLWVWSPCS

Q8TC59

protein_coding

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

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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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