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: RPA1

Gene summary for RPA1

Gene summary.

Gene information	Species	Human
	Gene symbol	RPA1
	Gene ID	6117
	Gene name	replication protein A1
	Gene Alias	HSSB
	Cytomap	17p13.3
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P27694

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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
6117	RPA1	HTA11_347_2000001011	Human	Colorectum	AD	6.76e-15	5.49e-01	-0.1954
6117	RPA1	HTA11_1391_2000001011	Human	Colorectum	AD	1.94e-06	5.44e-01	-0.059
6117	RPA1	HTA11_866_3004761011	Human	Colorectum	AD	4.80e-03	3.20e-01	0.096
6117	RPA1	HTA11_99999970781_79442	Human	Colorectum	MSS	1.17e-04	3.96e-01	0.294
6117	RPA1	HTA11_99999965104_69814	Human	Colorectum	MSS	1.23e-03	4.38e-01	0.281
6117	RPA1	A015-C-203	Human	Colorectum	FAP	2.44e-04	-3.36e-02	-0.1294
6117	RPA1	A001-C-108	Human	Colorectum	FAP	3.47e-02	-7.33e-02	-0.0272
6117	RPA1	A015-C-104	Human	Colorectum	FAP	3.90e-05	-2.20e-02	-0.1899
6117	RPA1	A002-C-116	Human	Colorectum	FAP	6.93e-03	1.71e-02	-0.0452
6117	RPA1	LZE2T	Human	Esophagus	ESCC	1.65e-03	3.61e-01	0.082
6117	RPA1	LZE4T	Human	Esophagus	ESCC	9.32e-25	6.73e-01	0.0811
6117	RPA1	LZE7T	Human	Esophagus	ESCC	1.43e-08	7.18e-01	0.0667
6117	RPA1	LZE8T	Human	Esophagus	ESCC	1.93e-03	1.92e-01	0.067
6117	RPA1	LZE24T	Human	Esophagus	ESCC	1.80e-18	5.30e-01	0.0596
6117	RPA1	LZE21T	Human	Esophagus	ESCC	1.13e-04	2.61e-01	0.0655
6117	RPA1	LZE6T	Human	Esophagus	ESCC	2.53e-03	2.79e-01	0.0845
6117	RPA1	P1T-E	Human	Esophagus	ESCC	7.99e-05	5.38e-01	0.0875
6117	RPA1	P2T-E	Human	Esophagus	ESCC	1.52e-30	6.63e-01	0.1177
6117	RPA1	P4T-E	Human	Esophagus	ESCC	1.83e-30	7.54e-01	0.1323
6117	RPA1	P5T-E	Human	Esophagus	ESCC	1.02e-05	1.57e-01	0.1327

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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:000037519	Oral cavity	OSCC	RNA splicing, via transesterification reactions	225/7305	324/18723	5.20e-29	2.99e-26	225
GO:000037719	Oral cavity	OSCC	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	221/7305	320/18723	5.50e-28	2.18e-25	221
GO:000039819	Oral cavity	OSCC	mRNA splicing, via spliceosome	221/7305	320/18723	5.50e-28	2.18e-25	221
GO:00062603	Oral cavity	OSCC	DNA replication	159/7305	260/18723	3.25e-13	1.59e-11	159
GO:000072316	Oral cavity	OSCC	telomere maintenance	85/7305	131/18723	1.72e-09	4.09e-08	85
GO:00718979	Oral cavity	OSCC	DNA biosynthetic process	106/7305	180/18723	4.86e-08	8.95e-07	106
GO:00323925	Oral cavity	OSCC	DNA geometric change	59/7305	90/18723	3.03e-07	4.63e-06	59
GO:00345023	Oral cavity	OSCC	protein localization to chromosome	60/7305	92/18723	3.17e-07	4.79e-06	60
GO:00325083	Oral cavity	OSCC	DNA duplex unwinding	55/7305	84/18723	8.05e-07	1.12e-05	55
GO:000700410	Oral cavity	OSCC	telomere maintenance via telomerase	46/7305	69/18723	3.00e-06	3.66e-05	46
GO:00063023	Oral cavity	OSCC	double-strand break repair	132/7305	251/18723	7.93e-06	8.52e-05	132
GO:00062611	Oral cavity	OSCC	DNA-dependent DNA replication	84/7305	151/18723	2.46e-05	2.30e-04	84
GO:001083316	Oral cavity	OSCC	telomere maintenance via telomere lengthening	50/7305	81/18723	2.87e-05	2.64e-04	50
GO:00062789	Oral cavity	OSCC	RNA-dependent DNA biosynthetic process	46/7305	75/18723	7.44e-05	5.81e-04	46
GO:00322006	Oral cavity	OSCC	telomere organization	85/7305	159/18723	1.47e-04	1.04e-03	85
GO:0006289	Oral cavity	OSCC	nucleotide-excision repair	37/7305	60/18723	3.15e-04	1.96e-03	37
GO:00062842	Oral cavity	OSCC	base-excision repair	28/7305	43/18723	4.71e-04	2.79e-03	28
GO:0006310	Oral cavity	OSCC	DNA recombination	147/7305	305/18723	6.33e-04	3.56e-03	147
GO:0000725	Oral cavity	OSCC	recombinational repair	70/7305	140/18723	5.22e-03	2.03e-02	70
GO:0000724	Oral cavity	OSCC	double-strand break repair via homologous recombination	69/7305	138/18723	5.52e-03	2.14e-02	69

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0342022	Esophagus	ESCC	Nucleotide excision repair	54/4205	63/8465	2.01e-09	2.17e-08	1.11e-08	54
hsa030304	Esophagus	ESCC	DNA replication	32/4205	36/8465	7.71e-07	5.06e-06	2.59e-06	32
hsa034304	Esophagus	ESCC	Mismatch repair	21/4205	23/8465	2.85e-05	1.35e-04	6.90e-05	21
hsa0342032	Esophagus	ESCC	Nucleotide excision repair	54/4205	63/8465	2.01e-09	2.17e-08	1.11e-08	54
hsa0303011	Esophagus	ESCC	DNA replication	32/4205	36/8465	7.71e-07	5.06e-06	2.59e-06	32
hsa0343011	Esophagus	ESCC	Mismatch repair	21/4205	23/8465	2.85e-05	1.35e-04	6.90e-05	21
hsa03420	Liver	Cirrhotic	Nucleotide excision repair	29/2530	63/8465	4.81e-03	1.74e-02	1.07e-02	29
hsa034201	Liver	Cirrhotic	Nucleotide excision repair	29/2530	63/8465	4.81e-03	1.74e-02	1.07e-02	29
hsa034202	Liver	HCC	Nucleotide excision repair	41/4020	63/8465	3.59e-03	1.12e-02	6.22e-03	41
hsa034203	Liver	HCC	Nucleotide excision repair	41/4020	63/8465	3.59e-03	1.12e-02	6.22e-03	41
hsa034204	Oral cavity	OSCC	Nucleotide excision repair	49/3704	63/8465	3.48e-08	2.91e-07	1.48e-07	49
hsa03030	Oral cavity	OSCC	DNA replication	31/3704	36/8465	1.70e-07	1.19e-06	6.03e-07	31
hsa03430	Oral cavity	OSCC	Mismatch repair	19/3704	23/8465	1.55e-04	5.34e-04	2.72e-04	19
hsa0342011	Oral cavity	OSCC	Nucleotide excision repair	49/3704	63/8465	3.48e-08	2.91e-07	1.48e-07	49
hsa030301	Oral cavity	OSCC	DNA replication	31/3704	36/8465	1.70e-07	1.19e-06	6.03e-07	31
hsa034301	Oral cavity	OSCC	Mismatch repair	19/3704	23/8465	1.55e-04	5.34e-04	2.72e-04	19
hsa0342021	Oral cavity	LP	Nucleotide excision repair	37/2418	63/8465	5.14e-07	6.33e-06	4.08e-06	37
hsa030302	Oral cavity	LP	DNA replication	23/2418	36/8465	1.08e-05	7.79e-05	5.02e-05	23
hsa034302	Oral cavity	LP	Mismatch repair	12/2418	23/8465	1.43e-02	4.59e-02	2.96e-02	12
hsa0342031	Oral cavity	LP	Nucleotide excision repair	37/2418	63/8465	5.14e-07	6.33e-06	4.08e-06	37

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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

RPA1

SNV

Missense_Mutation

rs865781874

c.1811N>A

p.Arg604Gln

p.R604Q

P27694

protein_coding

tolerated(0.09)

benign(0.142)

TCGA-BH-A42U-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RPA1

SNV

Missense_Mutation

c.1645N>A

p.Glu549Lys

p.E549K

P27694

protein_coding

tolerated(0.12)

benign(0.425)

TCGA-E2-A10C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

RPA1

insertion

Nonsense_Mutation

novel

c.577_578insGTCTATCTTTGCCTTATGTTAAAATATATTTTTAA

p.Tyr193CysfsTer12

p.Y193Cfs*12

P27694

protein_coding

TCGA-BH-A0B8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

RPA1

deletion

Frame_Shift_Del

novel

c.1758delN

p.Ile587LeufsTer5

p.I587Lfs*5

P27694

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

RPA1

SNV

Missense_Mutation

novel

c.979N>A

p.Glu327Lys

p.E327K

P27694

protein_coding

tolerated(0.19)

benign(0.233)

TCGA-C5-A8YR-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

RPA1

SNV

Missense_Mutation

c.1703N>T

p.Arg568Leu

p.R568L

P27694

protein_coding

deleterious(0.03)

benign(0.251)

TCGA-FU-A3EO-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

RPA1

SNV

Missense_Mutation

c.739C>G

p.Pro247Ala

p.P247A

P27694

protein_coding

tolerated(0.25)

benign(0.07)

TCGA-IR-A3LL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RPA1

SNV

Missense_Mutation

c.275N>C

p.Arg92Thr

p.R92T

P27694

protein_coding

tolerated(0.05)

benign(0.193)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RPA1

SNV

Missense_Mutation

c.215C>A

p.Ser72Tyr

p.S72Y

P27694

protein_coding

deleterious(0.02)

possibly_damaging(0.727)

TCGA-AA-3663-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

RPA1

SNV

Missense_Mutation

c.1358T>C

p.Leu453Pro

p.L453P

P27694

protein_coding

deleterious(0.01)

probably_damaging(0.995)

TCGA-AA-3663-01

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
6117	RPA1	DNA REPAIR, KINASE		NSC-15520	CHEMBL1765371	21459001

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