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: PYCR1

Gene summary for PYCR1

Gene summary.

Gene information	Species	Human
	Gene symbol	PYCR1
	Gene ID	5831
	Gene name	pyrroline-5-carboxylate reductase 1
	Gene Alias	ARCL2B
	Cytomap	17q25.3
	Gene Type	protein-coding
	GO ID	GO:0000302
	UniProtAcc	E2QRB3

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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
5831	PYCR1	LZE4T	Human	Esophagus	ESCC	4.22e-04	2.28e-01	0.0811
5831	PYCR1	LZE7T	Human	Esophagus	ESCC	1.75e-04	5.95e-01	0.0667
5831	PYCR1	LZE22T	Human	Esophagus	ESCC	2.03e-09	1.05e+00	0.068
5831	PYCR1	LZE24T	Human	Esophagus	ESCC	1.17e-28	9.56e-01	0.0596
5831	PYCR1	LZE21T	Human	Esophagus	ESCC	1.11e-03	5.15e-01	0.0655
5831	PYCR1	P1T-E	Human	Esophagus	ESCC	1.73e-06	5.48e-01	0.0875
5831	PYCR1	P2T-E	Human	Esophagus	ESCC	1.96e-44	1.02e+00	0.1177
5831	PYCR1	P4T-E	Human	Esophagus	ESCC	5.63e-35	9.85e-01	0.1323
5831	PYCR1	P5T-E	Human	Esophagus	ESCC	2.52e-37	8.35e-01	0.1327
5831	PYCR1	P8T-E	Human	Esophagus	ESCC	4.51e-09	2.29e-01	0.0889
5831	PYCR1	P9T-E	Human	Esophagus	ESCC	7.77e-05	2.81e-01	0.1131
5831	PYCR1	P10T-E	Human	Esophagus	ESCC	1.81e-50	1.05e+00	0.116
5831	PYCR1	P11T-E	Human	Esophagus	ESCC	2.44e-21	1.29e+00	0.1426
5831	PYCR1	P12T-E	Human	Esophagus	ESCC	5.66e-42	9.36e-01	0.1122
5831	PYCR1	P15T-E	Human	Esophagus	ESCC	2.91e-26	8.72e-01	0.1149
5831	PYCR1	P16T-E	Human	Esophagus	ESCC	1.62e-50	9.96e-01	0.1153
5831	PYCR1	P17T-E	Human	Esophagus	ESCC	4.35e-05	4.57e-01	0.1278
5831	PYCR1	P19T-E	Human	Esophagus	ESCC	1.38e-08	1.13e+00	0.1662
5831	PYCR1	P20T-E	Human	Esophagus	ESCC	8.98e-44	1.15e+00	0.1124
5831	PYCR1	P21T-E	Human	Esophagus	ESCC	4.82e-79	1.70e+00	0.1617

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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
Prostate		BPH: Benign Prostatic Hyperplasia
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:0006979111	Esophagus	ESCC	response to oxidative stress	303/8552	446/18723	7.15e-22	1.30e-19	303
GO:0062197111	Esophagus	ESCC	cellular response to chemical stress	234/8552	337/18723	5.37e-19	5.97e-17	234
GO:0034599111	Esophagus	ESCC	cellular response to oxidative stress	197/8552	288/18723	3.76e-15	2.15e-13	197
GO:0000302111	Esophagus	ESCC	response to reactive oxygen species	150/8552	222/18723	3.06e-11	1.02e-09	150
GO:0042542111	Esophagus	ESCC	response to hydrogen peroxide	102/8552	146/18723	2.64e-09	5.81e-08	102
GO:003461420	Esophagus	ESCC	cellular response to reactive oxygen species	103/8552	155/18723	1.34e-07	2.17e-06	103
GO:00703018	Esophagus	ESCC	cellular response to hydrogen peroxide	68/8552	98/18723	1.70e-06	2.03e-05	68
GO:005188110	Esophagus	ESCC	regulation of mitochondrial membrane potential	51/8552	74/18723	4.42e-05	3.51e-04	51
GO:00086525	Esophagus	ESCC	cellular amino acid biosynthetic process	51/8552	76/18723	1.30e-04	8.88e-04	51
GO:00463948	Esophagus	ESCC	carboxylic acid biosynthetic process	175/8552	314/18723	1.98e-04	1.26e-03	175
GO:00160538	Esophagus	ESCC	organic acid biosynthetic process	175/8552	316/18723	3.04e-04	1.82e-03	175
GO:19016075	Esophagus	ESCC	alpha-amino acid biosynthetic process	45/8552	68/18723	5.13e-04	2.84e-03	45
GO:003647320	Esophagus	ESCC	cell death in response to oxidative stress	59/8552	95/18723	9.12e-04	4.65e-03	59
GO:190288220	Esophagus	ESCC	regulation of response to oxidative stress	58/8552	98/18723	4.86e-03	1.88e-02	58
GO:190040720	Esophagus	ESCC	regulation of cellular response to oxidative stress	52/8552	89/18723	1.04e-02	3.56e-02	52
GO:190320120	Esophagus	ESCC	regulation of oxidative stress-induced cell death	44/8552	74/18723	1.18e-02	3.94e-02	44
GO:000697922	Liver	HCC	response to oxidative stress	281/7958	446/18723	9.75e-19	1.24e-16	281
GO:006219722	Liver	HCC	cellular response to chemical stress	216/7958	337/18723	6.86e-16	5.44e-14	216
GO:001605321	Liver	HCC	organic acid biosynthetic process	200/7958	316/18723	5.24e-14	3.22e-12	200
GO:004639421	Liver	HCC	carboxylic acid biosynthetic process	198/7958	314/18723	1.19e-13	6.78e-12	198

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
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
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
hsa0123031	Liver	HCC	Biosynthesis of amino acids	53/4020	75/8465	3.79e-05	2.11e-04	1.18e-04	53
hsa0033031	Liver	HCC	Arginine and proline metabolism	33/4020	50/8465	6.28e-03	1.77e-02	9.83e-03	33
hsa012305	Oral cavity	OSCC	Biosynthesis of amino acids	45/3704	75/8465	3.27e-03	8.23e-03	4.19e-03	45
hsa0033010	Oral cavity	OSCC	Arginine and proline metabolism	30/3704	50/8465	1.50e-02	3.26e-02	1.66e-02	30
hsa0123012	Oral cavity	OSCC	Biosynthesis of amino acids	45/3704	75/8465	3.27e-03	8.23e-03	4.19e-03	45
hsa0033013	Oral cavity	OSCC	Arginine and proline metabolism	30/3704	50/8465	1.50e-02	3.26e-02	1.66e-02	30
hsa0123022	Oral cavity	LP	Biosynthesis of amino acids	36/2418	75/8465	2.68e-04	1.51e-03	9.74e-04	36
hsa0033023	Oral cavity	LP	Arginine and proline metabolism	26/2418	50/8465	3.94e-04	2.08e-03	1.34e-03	26
hsa0123032	Oral cavity	LP	Biosynthesis of amino acids	36/2418	75/8465	2.68e-04	1.51e-03	9.74e-04	36
hsa0033033	Oral cavity	LP	Arginine and proline metabolism	26/2418	50/8465	3.94e-04	2.08e-03	1.34e-03	26
hsa0033022	Prostate	Tumor	Arginine and proline metabolism	19/1791	50/8465	4.73e-03	1.67e-02	1.03e-02	19
hsa0033032	Prostate	Tumor	Arginine and proline metabolism	19/1791	50/8465	4.73e-03	1.67e-02	1.03e-02	19

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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

PYCR1

SNV

Missense_Mutation

novel

c.373N>A

p.Gly125Ser

p.G125S

P32322

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AC-A23G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

PYCR1

deletion

Frame_Shift_Del

novel

c.848delN

p.Asn283ThrfsTer35

p.N283Tfs*35

P32322

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

PYCR1

deletion

Frame_Shift_Del

novel

c.115delG

p.Ala39LeufsTer19

p.A39Lfs*19

P32322

protein_coding

TCGA-S3-AA17-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

anastrozole

PYCR1

SNV

Missense_Mutation

rs281875318

c.850N>A

p.Ala284Thr

p.A284T

P32322

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PYCR1

SNV

Missense_Mutation

novel

c.295C>A

p.Pro99Thr

p.P99T

P32322

protein_coding

deleterious(0)

probably_damaging(0.968)

TCGA-Q1-A6DT-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

PYCR1

SNV

Missense_Mutation

rs746669423

c.872N>A

p.Arg291His

p.R291H

P32322

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-VS-A94Z-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

PYCR1

SNV

Missense_Mutation

rs748950222

c.691N>T

p.Arg231Cys

p.R231C

P32322

protein_coding

deleterious(0)

possibly_damaging(0.907)

TCGA-NH-A5IV-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

PYCR1

SNV

Missense_Mutation

rs771644421

c.376N>A

p.Val126Ile

p.V126I

P32322

protein_coding

tolerated(0.28)

benign(0.081)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

PYCR1

SNV

Missense_Mutation

novel

c.1027G>A

p.Ala343Thr

p.A343T

P32322

protein_coding

tolerated_low_confidence(0.25)

benign(0.007)

TCGA-B5-A1MX-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Hormone Therapy

megace

PYCR1

SNV

Missense_Mutation

rs139751598

c.616G>A

p.Ala206Thr

p.A206T

P32322

protein_coding

deleterious(0)

probably_damaging(0.918)

TCGA-B5-A3FC-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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