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: RPIA

Gene summary for RPIA

Gene summary.

Gene information	Species	Human
	Gene symbol	RPIA
	Gene ID	22934
	Gene name	ribose 5-phosphate isomerase A
	Gene Alias	RPI
	Cytomap	2p11.2
	Gene Type	protein-coding
	GO ID	GO:0005975
	UniProtAcc	P49247

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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
22934	RPIA	LZE2T	Human	Esophagus	ESCC	4.49e-06	5.67e-01	0.082
22934	RPIA	LZE4T	Human	Esophagus	ESCC	1.75e-04	1.95e-01	0.0811
22934	RPIA	LZE7T	Human	Esophagus	ESCC	1.80e-06	2.98e-01	0.0667
22934	RPIA	LZE8T	Human	Esophagus	ESCC	2.02e-05	2.82e-01	0.067
22934	RPIA	LZE22T	Human	Esophagus	ESCC	1.22e-02	3.81e-01	0.068
22934	RPIA	LZE24T	Human	Esophagus	ESCC	5.49e-15	4.33e-01	0.0596
22934	RPIA	LZE21T	Human	Esophagus	ESCC	1.05e-10	7.06e-01	0.0655
22934	RPIA	P1T-E	Human	Esophagus	ESCC	5.61e-04	3.78e-01	0.0875
22934	RPIA	P2T-E	Human	Esophagus	ESCC	1.40e-39	7.27e-01	0.1177
22934	RPIA	P4T-E	Human	Esophagus	ESCC	1.74e-23	6.29e-01	0.1323
22934	RPIA	P5T-E	Human	Esophagus	ESCC	8.55e-25	4.15e-01	0.1327
22934	RPIA	P8T-E	Human	Esophagus	ESCC	3.55e-38	7.54e-01	0.0889
22934	RPIA	P9T-E	Human	Esophagus	ESCC	9.56e-11	2.23e-01	0.1131
22934	RPIA	P10T-E	Human	Esophagus	ESCC	1.56e-29	5.16e-01	0.116
22934	RPIA	P11T-E	Human	Esophagus	ESCC	7.78e-03	2.09e-01	0.1426
22934	RPIA	P12T-E	Human	Esophagus	ESCC	7.97e-40	7.22e-01	0.1122
22934	RPIA	P15T-E	Human	Esophagus	ESCC	1.82e-43	9.90e-01	0.1149
22934	RPIA	P16T-E	Human	Esophagus	ESCC	2.19e-56	8.73e-01	0.1153
22934	RPIA	P17T-E	Human	Esophagus	ESCC	1.24e-06	3.16e-01	0.1278
22934	RPIA	P19T-E	Human	Esophagus	ESCC	2.80e-02	4.06e-01	0.1662

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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

∗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:0006091110	Esophagus	ESCC	generation of precursor metabolites and energy	331/8552	490/18723	3.86e-23	8.45e-21	331
GO:0019693111	Esophagus	ESCC	ribose phosphate metabolic process	234/8552	396/18723	4.24e-08	7.76e-07	234
GO:00059969	Esophagus	ESCC	monosaccharide metabolic process	159/8552	257/18723	1.11e-07	1.81e-06	159
GO:000674012	Esophagus	ESCC	NADPH regeneration	13/8552	16/18723	4.05e-03	1.62e-02	13
GO:000609812	Esophagus	ESCC	pentose-phosphate shunt	12/8552	15/18723	7.31e-03	2.63e-02	12
GO:00067393	Esophagus	ESCC	NADP metabolic process	23/8552	35/18723	1.34e-02	4.38e-02	23
GO:000609122	Liver	HCC	generation of precursor metabolites and energy	340/7958	490/18723	4.04e-34	2.85e-31	340
GO:001969322	Liver	HCC	ribose phosphate metabolic process	248/7958	396/18723	3.15e-16	2.70e-14	248
GO:000599621	Liver	HCC	monosaccharide metabolic process	167/7958	257/18723	2.31e-13	1.25e-11	167
GO:00067401	Liver	HCC	NADPH regeneration	14/7958	16/18723	2.73e-04	1.98e-03	14
GO:0006739	Liver	HCC	NADP metabolic process	25/7958	35/18723	5.05e-04	3.29e-03	25
GO:00060981	Liver	HCC	pentose-phosphate shunt	13/7958	15/18723	5.67e-04	3.61e-03	13
GO:000609118	Oral cavity	OSCC	generation of precursor metabolites and energy	286/7305	490/18723	1.45e-18	1.71e-16	286
GO:001969319	Oral cavity	OSCC	ribose phosphate metabolic process	199/7305	396/18723	2.97e-06	3.64e-05	199
GO:00059968	Oral cavity	OSCC	monosaccharide metabolic process	129/7305	257/18723	1.63e-04	1.13e-03	129
GO:00067392	Oral cavity	OSCC	NADP metabolic process	22/7305	35/18723	3.65e-03	1.51e-02	22
GO:00067402	Oral cavity	OSCC	NADPH regeneration	12/7305	16/18723	3.83e-03	1.57e-02	12
GO:00060982	Oral cavity	OSCC	pentose-phosphate shunt	11/7305	15/18723	7.49e-03	2.75e-02	11
GO:000609119	Oral cavity	LP	generation of precursor metabolites and energy	214/4623	490/18723	1.12e-20	2.60e-18	214
GO:000674011	Oral cavity	LP	NADPH regeneration	11/4623	16/18723	2.52e-04	2.63e-03	11

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0120023	Esophagus	ESCC	Carbon metabolism	79/4205	115/8465	2.50e-05	1.21e-04	6.22e-05	79
hsa0123023	Esophagus	ESCC	Biosynthesis of amino acids	49/4205	75/8465	4.35e-03	1.12e-02	5.74e-03	49
hsa0120033	Esophagus	ESCC	Carbon metabolism	79/4205	115/8465	2.50e-05	1.21e-04	6.22e-05	79
hsa0123033	Esophagus	ESCC	Biosynthesis of amino acids	49/4205	75/8465	4.35e-03	1.12e-02	5.74e-03	49
hsa0120041	Liver	HCC	Carbon metabolism	89/4020	115/8465	3.92e-11	6.56e-10	3.65e-10	89
hsa0123021	Liver	HCC	Biosynthesis of amino acids	53/4020	75/8465	3.79e-05	2.11e-04	1.18e-04	53
hsa000302	Liver	HCC	Pentose phosphate pathway	21/4020	30/8465	1.06e-02	2.71e-02	1.51e-02	21
hsa0120051	Liver	HCC	Carbon metabolism	89/4020	115/8465	3.92e-11	6.56e-10	3.65e-10	89
hsa0123031	Liver	HCC	Biosynthesis of amino acids	53/4020	75/8465	3.79e-05	2.11e-04	1.18e-04	53
hsa000303	Liver	HCC	Pentose phosphate pathway	21/4020	30/8465	1.06e-02	2.71e-02	1.51e-02	21
hsa0120014	Oral cavity	OSCC	Carbon metabolism	74/3704	115/8465	6.10e-06	3.05e-05	1.55e-05	74
hsa012305	Oral cavity	OSCC	Biosynthesis of amino acids	45/3704	75/8465	3.27e-03	8.23e-03	4.19e-03	45
hsa0120015	Oral cavity	OSCC	Carbon metabolism	74/3704	115/8465	6.10e-06	3.05e-05	1.55e-05	74
hsa0123012	Oral cavity	OSCC	Biosynthesis of amino acids	45/3704	75/8465	3.27e-03	8.23e-03	4.19e-03	45
hsa0120022	Oral cavity	LP	Carbon metabolism	62/2418	115/8465	8.38e-09	1.39e-07	8.99e-08	62
hsa0123022	Oral cavity	LP	Biosynthesis of amino acids	36/2418	75/8465	2.68e-04	1.51e-03	9.74e-04	36
hsa0120032	Oral cavity	LP	Carbon metabolism	62/2418	115/8465	8.38e-09	1.39e-07	8.99e-08	62
hsa0123032	Oral cavity	LP	Biosynthesis of amino acids	36/2418	75/8465	2.68e-04	1.51e-03	9.74e-04	36

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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

RPIA

SNV

Missense_Mutation

novel

c.724G>C

p.Ala242Pro

p.A242P

P49247

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-B6-A0RE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

RPIA

insertion

Nonsense_Mutation

novel

c.725_726insCTTTAAAAATTAAAAGTTAAGTTTCTCTTTAAG

p.Ala242_Val243insPheLysAsnTerLysLeuSerPheSerLeuSer

p.A242_V243insFKN*KLSFSLS

P49247

protein_coding

TCGA-B6-A0RE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

RPIA

insertion

In_Frame_Ins

novel

c.710_711insAAGTGCCAGGAT

p.Val237_Glu238insSerAlaArgIle

p.V237_E238insSARI

P49247

protein_coding

TCGA-BH-A0BM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

RPIA

SNV

Missense_Mutation

novel

c.308N>C

p.Gly103Ala

p.G103A

P49247

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-MA-AA41-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

RPIA

deletion

Frame_Shift_Del

novel

c.149_153delGGACC

p.Gly50AlafsTer46

p.G50Afs*46

P49247

protein_coding

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

RPIA

SNV

Missense_Mutation

rs375132883

c.406N>T

p.Arg136Cys

p.R136C

P49247

protein_coding

deleterious(0)

probably_damaging(0.985)

TCGA-5M-AAT6-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Unknown

RPIA

SNV

Missense_Mutation

c.847N>A

p.Asp283Asn

p.D283N

P49247

protein_coding

deleterious(0)

possibly_damaging(0.881)

TCGA-AA-3715-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

RPIA

SNV

Missense_Mutation

c.586G>A

p.Ala196Thr

p.A196T

P49247

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AA-A00N-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

RPIA

SNV

Missense_Mutation

c.549N>T

p.Lys183Asn

p.K183N

P49247

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

RPIA

SNV

Missense_Mutation

c.549N>T

p.Lys183Asn

p.K183N

P49247

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AZ-4315-01

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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