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: PPIL2

Gene summary for PPIL2

Gene summary.

Gene information	Species	Human
	Gene symbol	PPIL2
	Gene ID	23759
	Gene name	peptidylprolyl isomerase like 2
	Gene Alias	CYC4
	Cytomap	22q11.21-q11.22
	Gene Type	protein-coding
	GO ID	GO:0000209
	UniProtAcc	A0A024R1C1

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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
23759	PPIL2	LZE4T	Human	Esophagus	ESCC	1.78e-06	2.53e-01	0.0811
23759	PPIL2	LZE5T	Human	Esophagus	ESCC	1.36e-06	3.97e-01	0.0514
23759	PPIL2	LZE7T	Human	Esophagus	ESCC	1.30e-05	3.00e-01	0.0667
23759	PPIL2	LZE8T	Human	Esophagus	ESCC	3.84e-03	1.71e-01	0.067
23759	PPIL2	LZE20T	Human	Esophagus	ESCC	3.87e-04	2.01e-01	0.0662
23759	PPIL2	LZE22T	Human	Esophagus	ESCC	1.24e-02	3.18e-01	0.068
23759	PPIL2	LZE24T	Human	Esophagus	ESCC	1.01e-06	2.14e-01	0.0596
23759	PPIL2	LZE21T	Human	Esophagus	ESCC	3.39e-07	4.91e-01	0.0655
23759	PPIL2	LZE6T	Human	Esophagus	ESCC	2.50e-02	1.54e-01	0.0845
23759	PPIL2	P1T-E	Human	Esophagus	ESCC	6.42e-18	6.10e-01	0.0875
23759	PPIL2	P2T-E	Human	Esophagus	ESCC	1.93e-13	2.23e-01	0.1177
23759	PPIL2	P4T-E	Human	Esophagus	ESCC	6.42e-15	3.51e-01	0.1323
23759	PPIL2	P5T-E	Human	Esophagus	ESCC	5.07e-04	6.88e-02	0.1327
23759	PPIL2	P8T-E	Human	Esophagus	ESCC	6.72e-22	3.34e-01	0.0889
23759	PPIL2	P9T-E	Human	Esophagus	ESCC	3.14e-11	2.84e-01	0.1131
23759	PPIL2	P10T-E	Human	Esophagus	ESCC	1.29e-22	4.29e-01	0.116
23759	PPIL2	P11T-E	Human	Esophagus	ESCC	2.07e-07	3.18e-01	0.1426
23759	PPIL2	P12T-E	Human	Esophagus	ESCC	9.39e-21	4.20e-01	0.1122
23759	PPIL2	P15T-E	Human	Esophagus	ESCC	7.94e-15	3.38e-01	0.1149
23759	PPIL2	P16T-E	Human	Esophagus	ESCC	3.75e-11	2.97e-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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:0006457110	Esophagus	ESCC	protein folding	163/8552	212/18723	1.13e-20	1.74e-18	163
GO:000020917	Esophagus	ESCC	protein polyubiquitination	170/8552	236/18723	1.40e-16	1.09e-14	170
GO:0072659110	Esophagus	ESCC	protein localization to plasma membrane	193/8552	284/18723	1.95e-14	1.03e-12	193
GO:199077819	Esophagus	ESCC	protein localization to cell periphery	217/8552	333/18723	4.08e-13	1.88e-11	217
GO:001820816	Esophagus	ESCC	peptidyl-proline modification	46/8552	58/18723	1.59e-07	2.51e-06	46
GO:000041313	Esophagus	ESCC	protein peptidyl-prolyl isomerization	32/8552	42/18723	5.52e-05	4.27e-04	32
GO:00002095	Liver	NAFLD	protein polyubiquitination	51/1882	236/18723	1.04e-07	8.10e-06	51
GO:00726597	Liver	NAFLD	protein localization to plasma membrane	51/1882	284/18723	2.97e-05	7.83e-04	51
GO:19907786	Liver	NAFLD	protein localization to cell periphery	56/1882	333/18723	8.29e-05	1.69e-03	56
GO:000645712	Liver	HCC	protein folding	160/7958	212/18723	1.07e-22	1.88e-20	160
GO:007265921	Liver	HCC	protein localization to plasma membrane	177/7958	284/18723	1.02e-11	4.18e-10	177
GO:000020921	Liver	HCC	protein polyubiquitination	151/7958	236/18723	1.90e-11	7.59e-10	151
GO:199077821	Liver	HCC	protein localization to cell periphery	200/7958	333/18723	6.07e-11	2.23e-09	200
GO:001820811	Liver	HCC	peptidyl-proline modification	42/7958	58/18723	3.73e-06	4.85e-05	42
GO:00004131	Liver	HCC	protein peptidyl-prolyl isomerization	31/7958	42/18723	3.83e-05	3.80e-04	31
GO:000645718	Oral cavity	OSCC	protein folding	154/7305	212/18723	1.89e-23	4.60e-21	154
GO:000020910	Oral cavity	OSCC	protein polyubiquitination	150/7305	236/18723	1.59e-14	9.27e-13	150
GO:007265918	Oral cavity	OSCC	protein localization to plasma membrane	169/7305	284/18723	1.69e-12	7.21e-11	169
GO:199077816	Oral cavity	OSCC	protein localization to cell periphery	190/7305	333/18723	1.46e-11	5.13e-10	190
GO:00182088	Oral cavity	OSCC	peptidyl-proline modification	42/7305	58/18723	2.49e-07	3.92e-06	42

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0412027	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0412036	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0412010	Liver	NAFLD	Ubiquitin mediated proteolysis	44/1043	142/8465	2.59e-09	1.70e-07	1.37e-07	44
hsa0412011	Liver	NAFLD	Ubiquitin mediated proteolysis	44/1043	142/8465	2.59e-09	1.70e-07	1.37e-07	44
hsa0412041	Liver	HCC	Ubiquitin mediated proteolysis	110/4020	142/8465	1.67e-13	3.74e-12	2.08e-12	110
hsa0412051	Liver	HCC	Ubiquitin mediated proteolysis	110/4020	142/8465	1.67e-13	3.74e-12	2.08e-12	110
hsa0412020	Oral cavity	OSCC	Ubiquitin mediated proteolysis	105/3704	142/8465	1.83e-13	4.37e-12	2.23e-12	105
hsa04120110	Oral cavity	OSCC	Ubiquitin mediated proteolysis	105/3704	142/8465	1.83e-13	4.37e-12	2.23e-12	105
hsa0412025	Oral cavity	LP	Ubiquitin mediated proteolysis	66/2418	142/8465	3.74e-06	3.46e-05	2.23e-05	66
hsa0412035	Oral cavity	LP	Ubiquitin mediated proteolysis	66/2418	142/8465	3.74e-06	3.46e-05	2.23e-05	66

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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

PPIL2

SNV

Missense_Mutation

c.128N>T

p.Ser43Ile

p.S43I

Q13356

protein_coding

deleterious(0.01)

benign(0.192)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

PPIL2

SNV

Missense_Mutation

novel

c.1143N>A

p.Phe381Leu

p.F381L

Q13356

protein_coding

deleterious(0)

possibly_damaging(0.818)

TCGA-A8-A06X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PPIL2

SNV

Missense_Mutation

c.922A>T

p.Ile308Phe

p.I308F

Q13356

protein_coding

deleterious(0)

benign(0.288)

TCGA-C8-A274-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

PPIL2

SNV

Missense_Mutation

c.419N>G

p.Asn140Ser

p.N140S

Q13356

protein_coding

tolerated(0.12)

benign(0.031)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PPIL2

insertion

Frame_Shift_Ins

novel

c.58_59insGTCTCCCCCGTCCCCCAGGCTGGAGTGT

p.His20ArgfsTer30

p.H20Rfs*30

Q13356

protein_coding

TCGA-B6-A0IK-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

PPIL2

SNV

Missense_Mutation

novel

c.814N>T

p.Arg272Cys

p.R272C

Q13356

protein_coding

deleterious(0)

probably_damaging(0.983)

TCGA-HM-A4S6-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

PPIL2

SNV

Missense_Mutation

c.348N>G

p.Ile116Met

p.I116M

Q13356

protein_coding

deleterious(0)

probably_damaging(0.989)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

PPIL2

deletion

In_Frame_Del

novel

c.845_853delNNNNNNNNN

p.Val282_His285delinsAsp

p.V282_H285delinsD

Q13356

protein_coding

TCGA-EK-A2RB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

PPIL2

SNV

Missense_Mutation

rs201854982

c.442G>A

p.Glu148Lys

p.E148K

Q13356

protein_coding

deleterious(0.04)

benign(0.286)

TCGA-AA-3715-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

PPIL2

SNV

Missense_Mutation

c.1009G>T

p.Gly337Cys

p.G337C

Q13356

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AD-5900-01

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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