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: PYCR2

Gene summary for PYCR2

Gene summary.

Gene information	Species	Human
	Gene symbol	PYCR2
	Gene ID	29920
	Gene name	pyrroline-5-carboxylate reductase 2
	Gene Alias	HLD10
	Cytomap	1q42.12
	Gene Type	protein-coding
	GO ID	GO:0006082
	UniProtAcc	A0A087WTV6

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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
29920	PYCR2	HTA11_3410_2000001011	Human	Colorectum	AD	2.29e-05	1.54e-01	0.0155
29920	PYCR2	HTA11_2487_2000001011	Human	Colorectum	SER	3.37e-03	1.71e-01	-0.1808
29920	PYCR2	HTA11_2951_2000001011	Human	Colorectum	AD	3.40e-03	2.22e-01	0.0216
29920	PYCR2	HTA11_1938_2000001011	Human	Colorectum	AD	8.45e-11	3.82e-01	-0.0811
29920	PYCR2	HTA11_78_2000001011	Human	Colorectum	AD	8.26e-09	2.42e-01	-0.1088
29920	PYCR2	HTA11_347_2000001011	Human	Colorectum	AD	2.51e-09	2.09e-01	-0.1954
29920	PYCR2	HTA11_411_2000001011	Human	Colorectum	SER	5.61e-03	2.55e-01	-0.2602
29920	PYCR2	HTA11_3361_2000001011	Human	Colorectum	AD	2.57e-07	2.67e-01	-0.1207
29920	PYCR2	HTA11_83_2000001011	Human	Colorectum	SER	1.79e-04	1.91e-01	-0.1526
29920	PYCR2	HTA11_696_2000001011	Human	Colorectum	AD	1.96e-10	2.47e-01	-0.1464
29920	PYCR2	HTA11_866_2000001011	Human	Colorectum	AD	2.07e-07	1.85e-01	-0.1001
29920	PYCR2	HTA11_1391_2000001011	Human	Colorectum	AD	1.53e-17	3.66e-01	-0.059
29920	PYCR2	HTA11_2992_2000001011	Human	Colorectum	SER	1.72e-05	2.63e-01	-0.1706
29920	PYCR2	HTA11_5212_2000001011	Human	Colorectum	AD	2.28e-02	1.70e-01	-0.2061
29920	PYCR2	HTA11_5216_2000001011	Human	Colorectum	SER	3.40e-02	2.52e-01	-0.1462
29920	PYCR2	HTA11_546_2000001011	Human	Colorectum	AD	7.78e-03	1.68e-01	-0.0842
29920	PYCR2	HTA11_7862_2000001011	Human	Colorectum	AD	1.12e-06	2.52e-01	-0.0179
29920	PYCR2	HTA11_866_3004761011	Human	Colorectum	AD	1.60e-16	3.65e-01	0.096
29920	PYCR2	HTA11_4255_2000001011	Human	Colorectum	SER	3.40e-03	2.22e-01	0.0446
29920	PYCR2	HTA11_8622_2000001021	Human	Colorectum	SER	8.37e-05	2.67e-01	0.0528

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal 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
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ

∗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:0006979	Colorectum	AD	response to oxidative stress	145/3918	446/18723	5.16e-09	3.23e-07	145
GO:0062197	Colorectum	AD	cellular response to chemical stress	109/3918	337/18723	5.33e-07	1.95e-05	109
GO:0034599	Colorectum	AD	cellular response to oxidative stress	94/3918	288/18723	2.03e-06	6.02e-05	94
GO:0006520	Colorectum	AD	cellular amino acid metabolic process	81/3918	284/18723	1.37e-03	1.19e-02	81
GO:00069791	Colorectum	SER	response to oxidative stress	114/2897	446/18723	1.75e-08	1.28e-06	114
GO:00621971	Colorectum	SER	cellular response to chemical stress	87/2897	337/18723	5.33e-07	2.59e-05	87
GO:00345991	Colorectum	SER	cellular response to oxidative stress	73/2897	288/18723	8.52e-06	2.86e-04	73
GO:00065201	Colorectum	SER	cellular amino acid metabolic process	61/2897	284/18723	4.20e-03	3.41e-02	61
GO:00069792	Colorectum	MSS	response to oxidative stress	128/3467	446/18723	7.65e-08	3.81e-06	128
GO:00621972	Colorectum	MSS	cellular response to chemical stress	102/3467	337/18723	9.73e-08	4.71e-06	102
GO:00345992	Colorectum	MSS	cellular response to oxidative stress	88/3467	288/18723	4.58e-07	1.77e-05	88
GO:0046394	Colorectum	MSS	carboxylic acid biosynthetic process	76/3467	314/18723	6.71e-03	4.38e-02	76
GO:0016053	Colorectum	MSS	organic acid biosynthetic process	76/3467	316/18723	7.88e-03	4.84e-02	76
GO:00069793	Colorectum	MSI-H	response to oxidative stress	68/1319	446/18723	1.17e-09	1.59e-07	68
GO:00621973	Colorectum	MSI-H	cellular response to chemical stress	51/1319	337/18723	1.78e-07	1.52e-05	51
GO:00345993	Colorectum	MSI-H	cellular response to oxidative stress	43/1319	288/18723	2.31e-06	1.40e-04	43
GO:1901605	Colorectum	MSI-H	alpha-amino acid metabolic process	26/1319	195/18723	1.26e-03	2.02e-02	26
GO:0008652	Colorectum	MSI-H	cellular amino acid biosynthetic process	13/1319	76/18723	2.35e-03	3.12e-02	13
GO:1901607	Colorectum	MSI-H	alpha-amino acid biosynthetic process	12/1319	68/18723	2.60e-03	3.41e-02	12
GO:00463941	Colorectum	MSI-H	carboxylic acid biosynthetic process	36/1319	314/18723	2.68e-03	3.48e-02	36

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa00330	Colorectum	AD	Arginine and proline metabolism	23/2092	50/8465	8.27e-04	5.90e-03	3.76e-03	23
hsa01230	Colorectum	AD	Biosynthesis of amino acids	28/2092	75/8465	9.99e-03	3.89e-02	2.48e-02	28
hsa003301	Colorectum	AD	Arginine and proline metabolism	23/2092	50/8465	8.27e-04	5.90e-03	3.76e-03	23
hsa012301	Colorectum	AD	Biosynthesis of amino acids	28/2092	75/8465	9.99e-03	3.89e-02	2.48e-02	28
hsa003302	Colorectum	SER	Arginine and proline metabolism	17/1580	50/8465	7.12e-03	3.77e-02	2.74e-02	17
hsa012302	Colorectum	SER	Biosynthesis of amino acids	23/1580	75/8465	8.11e-03	4.14e-02	3.01e-02	23
hsa003303	Colorectum	SER	Arginine and proline metabolism	17/1580	50/8465	7.12e-03	3.77e-02	2.74e-02	17
hsa012303	Colorectum	SER	Biosynthesis of amino acids	23/1580	75/8465	8.11e-03	4.14e-02	3.01e-02	23
hsa003304	Colorectum	MSS	Arginine and proline metabolism	23/1875	50/8465	1.52e-04	1.24e-03	7.61e-04	23
hsa003305	Colorectum	MSS	Arginine and proline metabolism	23/1875	50/8465	1.52e-04	1.24e-03	7.61e-04	23
hsa012306	Esophagus	HGIN	Biosynthesis of amino acids	21/1383	75/8465	7.38e-03	4.63e-02	3.68e-02	21
hsa0123013	Esophagus	HGIN	Biosynthesis of amino acids	21/1383	75/8465	7.38e-03	4.63e-02	3.68e-02	21
hsa0123023	Esophagus	ESCC	Biosynthesis of amino acids	49/4205	75/8465	4.35e-03	1.12e-02	5.74e-03	49
hsa0123033	Esophagus	ESCC	Biosynthesis of amino acids	49/4205	75/8465	4.35e-03	1.12e-02	5.74e-03	49
hsa012304	Liver	Cirrhotic	Biosynthesis of amino acids	35/2530	75/8465	1.54e-03	7.83e-03	4.83e-03	35
hsa003308	Liver	Cirrhotic	Arginine and proline metabolism	25/2530	50/8465	2.18e-03	9.41e-03	5.80e-03	25
hsa0123011	Liver	Cirrhotic	Biosynthesis of amino acids	35/2530	75/8465	1.54e-03	7.83e-03	4.83e-03	35
hsa0033011	Liver	Cirrhotic	Arginine and proline metabolism	25/2530	50/8465	2.18e-03	9.41e-03	5.80e-03	25
hsa0123021	Liver	HCC	Biosynthesis of amino acids	53/4020	75/8465	3.79e-05	2.11e-04	1.18e-04	53
hsa0033021	Liver	HCC	Arginine and proline metabolism	33/4020	50/8465	6.28e-03	1.77e-02	9.83e-03	33

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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

PYCR2

SNV

Missense_Mutation

rs538606802

c.427N>T

p.Val143Leu

p.V143L

Q96C36

protein_coding

tolerated(0.31)

benign(0)

TCGA-A2-A0ET-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

PYCR2

SNV

Missense_Mutation

c.536N>T

p.Ala179Val

p.A179V

Q96C36

protein_coding

deleterious(0)

probably_damaging(0.969)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PYCR2

SNV

Missense_Mutation

novel

c.712N>C

p.Thr238Pro

p.T238P

Q96C36

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AR-A1AP-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

PYCR2

SNV

Missense_Mutation

novel

c.712N>C

p.Thr238Pro

p.T238P

Q96C36

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-D8-A1X6-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

PYCR2

SNV

Missense_Mutation

rs754486659

c.287N>T

p.Ala96Val

p.A96V

Q96C36

protein_coding

deleterious(0.02)

probably_damaging(0.996)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

PYCR2

SNV

Missense_Mutation

novel

c.868N>A

p.Val290Met

p.V290M

Q96C36

protein_coding

tolerated_low_confidence(0.05)

benign(0.188)

TCGA-AJ-A2QN-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PYCR2

SNV

Missense_Mutation

novel

c.268N>T

p.His90Tyr

p.H90Y

Q96C36

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AJ-A3BG-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

carboplatin

PYCR2

SNV

Missense_Mutation

c.142A>G

p.Met48Val

p.M48V

Q96C36

protein_coding

tolerated(0.1)

benign(0.001)

TCGA-AP-A056-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PYCR2

SNV

Missense_Mutation

c.394N>A

p.Ala132Thr

p.A132T

Q96C36

protein_coding

deleterious(0.01)

possibly_damaging(0.696)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

PYCR2

SNV

Missense_Mutation

novel

c.742N>A

p.Gly248Arg

p.G248R

Q96C36

protein_coding

deleterious(0.04)

possibly_damaging(0.621)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

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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