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: XPA

Gene summary for XPA

Gene summary.

Gene information	Species	Human
	Gene symbol	XPA
	Gene ID	7507
	Gene name	XPA, DNA damage recognition and repair factor
	Gene Alias	XP1
	Cytomap	9q22.33
	Gene Type	protein-coding
	GO ID	GO:0000715
	UniProtAcc	P23025

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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
7507	XPA	P128T-E	Human	Esophagus	ESCC	7.18e-23	6.10e-01	0.1241
7507	XPA	P130T-E	Human	Esophagus	ESCC	4.52e-15	3.06e-01	0.1676
7507	XPA	HCC1_Meng	Human	Liver	HCC	1.52e-53	-6.87e-02	0.0246
7507	XPA	HCC2_Meng	Human	Liver	HCC	6.37e-17	-2.45e-02	0.0107
7507	XPA	cirrhotic1	Human	Liver	Cirrhotic	6.13e-06	1.85e-01	0.0202
7507	XPA	HCC1	Human	Liver	HCC	6.60e-03	3.52e+00	0.5336
7507	XPA	Pt13.b	Human	Liver	HCC	3.37e-04	1.72e-02	0.0251
7507	XPA	S014	Human	Liver	HCC	6.78e-03	3.13e-01	0.2254
7507	XPA	S016	Human	Liver	HCC	2.29e-02	2.83e-01	0.2243
7507	XPA	S027	Human	Liver	HCC	2.79e-06	7.91e-01	0.2446
7507	XPA	S028	Human	Liver	HCC	4.24e-17	9.41e-01	0.2503
7507	XPA	S029	Human	Liver	HCC	6.31e-17	1.08e+00	0.2581
7507	XPA	C04	Human	Oral cavity	OSCC	1.47e-17	8.25e-01	0.2633
7507	XPA	C21	Human	Oral cavity	OSCC	9.04e-23	8.02e-01	0.2678
7507	XPA	C30	Human	Oral cavity	OSCC	4.16e-16	7.82e-01	0.3055
7507	XPA	C38	Human	Oral cavity	OSCC	5.98e-17	1.29e+00	0.172
7507	XPA	C43	Human	Oral cavity	OSCC	6.20e-04	1.94e-01	0.1704
7507	XPA	C46	Human	Oral cavity	OSCC	2.49e-26	6.15e-01	0.1673
7507	XPA	C51	Human	Oral cavity	OSCC	3.93e-04	3.03e-01	0.2674
7507	XPA	C57	Human	Oral cavity	OSCC	7.13e-07	2.06e-01	0.1679

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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
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
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:003450417	Esophagus	HGIN	protein localization to nucleus	84/2587	290/18723	1.06e-11	1.24e-09	84
GO:000931418	Esophagus	HGIN	response to radiation	88/2587	456/18723	6.26e-04	8.65e-03	88
GO:00714789	Esophagus	HGIN	cellular response to radiation	42/2587	186/18723	7.66e-04	1.00e-02	42
GO:00094115	Esophagus	HGIN	response to UV	35/2587	149/18723	9.71e-04	1.22e-02	35
GO:007121418	Esophagus	HGIN	cellular response to abiotic stimulus	66/2587	331/18723	1.21e-03	1.45e-02	66
GO:010400418	Esophagus	HGIN	cellular response to environmental stimulus	66/2587	331/18723	1.21e-03	1.45e-02	66
GO:00346445	Esophagus	HGIN	cellular response to UV	23/2587	90/18723	2.16e-03	2.25e-02	23
GO:00094165	Esophagus	HGIN	response to light stimulus	61/2587	320/18723	5.20e-03	4.30e-02	61
GO:00062892	Esophagus	HGIN	nucleotide-excision repair	16/2587	60/18723	6.22e-03	4.95e-02	16
GO:003450418	Esophagus	ESCC	protein localization to nucleus	211/8552	290/18723	4.06e-21	6.60e-19	211
GO:000941113	Esophagus	ESCC	response to UV	115/8552	149/18723	3.29e-15	1.93e-13	115
GO:000931419	Esophagus	ESCC	response to radiation	277/8552	456/18723	4.42e-11	1.43e-09	277
GO:003464413	Esophagus	ESCC	cellular response to UV	70/8552	90/18723	4.59e-10	1.20e-08	70
GO:007121419	Esophagus	ESCC	cellular response to abiotic stimulus	206/8552	331/18723	7.52e-10	1.88e-08	206
GO:010400419	Esophagus	ESCC	cellular response to environmental stimulus	206/8552	331/18723	7.52e-10	1.88e-08	206
GO:00903053	Esophagus	ESCC	nucleic acid phosphodiester bond hydrolysis	163/8552	261/18723	3.07e-08	5.73e-07	163
GO:007147816	Esophagus	ESCC	cellular response to radiation	122/8552	186/18723	3.07e-08	5.73e-07	122
GO:000941611	Esophagus	ESCC	response to light stimulus	183/8552	320/18723	2.03e-05	1.76e-04	183
GO:00062843	Esophagus	ESCC	base-excision repair	33/8552	43/18723	3.25e-05	2.69e-04	33
GO:00062891	Esophagus	ESCC	nucleotide-excision repair	42/8552	60/18723	1.18e-04	8.14e-04	42

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa034205	Esophagus	HGIN	Nucleotide excision repair	29/1383	63/8465	2.96e-08	5.36e-07	4.26e-07	29
hsa0342012	Esophagus	HGIN	Nucleotide excision repair	29/1383	63/8465	2.96e-08	5.36e-07	4.26e-07	29
hsa0342022	Esophagus	ESCC	Nucleotide excision repair	54/4205	63/8465	2.01e-09	2.17e-08	1.11e-08	54
hsa015247	Esophagus	ESCC	Platinum drug resistance	56/4205	73/8465	1.85e-06	1.13e-05	5.78e-06	56
hsa0342032	Esophagus	ESCC	Nucleotide excision repair	54/4205	63/8465	2.01e-09	2.17e-08	1.11e-08	54
hsa0152414	Esophagus	ESCC	Platinum drug resistance	56/4205	73/8465	1.85e-06	1.13e-05	5.78e-06	56
hsa015244	Liver	Cirrhotic	Platinum drug resistance	34/2530	73/8465	1.86e-03	8.37e-03	5.16e-03	34
hsa03420	Liver	Cirrhotic	Nucleotide excision repair	29/2530	63/8465	4.81e-03	1.74e-02	1.07e-02	29
hsa0152411	Liver	Cirrhotic	Platinum drug resistance	34/2530	73/8465	1.86e-03	8.37e-03	5.16e-03	34
hsa034201	Liver	Cirrhotic	Nucleotide excision repair	29/2530	63/8465	4.81e-03	1.74e-02	1.07e-02	29
hsa015242	Liver	HCC	Platinum drug resistance	52/4020	73/8465	3.14e-05	1.88e-04	1.04e-04	52
hsa034202	Liver	HCC	Nucleotide excision repair	41/4020	63/8465	3.59e-03	1.12e-02	6.22e-03	41
hsa015243	Liver	HCC	Platinum drug resistance	52/4020	73/8465	3.14e-05	1.88e-04	1.04e-04	52
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
hsa015246	Oral cavity	OSCC	Platinum drug resistance	51/3704	73/8465	5.41e-06	2.75e-05	1.40e-05	51
hsa0342011	Oral cavity	OSCC	Nucleotide excision repair	49/3704	63/8465	3.48e-08	2.91e-07	1.48e-07	49
hsa0152413	Oral cavity	OSCC	Platinum drug resistance	51/3704	73/8465	5.41e-06	2.75e-05	1.40e-05	51
hsa0342021	Oral cavity	LP	Nucleotide excision repair	37/2418	63/8465	5.14e-07	6.33e-06	4.08e-06	37
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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
XPA	ECM	Cervix	ADJ	TIMP1,FJX1,ZNF737, etc.	2.87e-01
XPA	INCAF	Cervix	CC	TIMP1,FJX1,ZNF737, etc.	3.10e-01

∗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

XPA

SNV

Missense_Mutation

novel

c.765N>G

p.Asp255Glu

p.D255E

P23025

protein_coding

deleterious(0.04)

benign(0.141)

TCGA-MS-A51U-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

XPA

SNV

Missense_Mutation

c.569C>T

p.Ser190Phe

p.S190F

P23025

protein_coding

deleterious(0)

possibly_damaging(0.52)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

XPA

insertion

In_Frame_Ins

novel

c.743_744insTAAAACCATAAAAACCCT

p.Pro248_Glu249insLysThrIleLysThrLeu

p.P248_E249insKTIKTL

P23025

protein_coding

TCGA-DS-A1OD-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

XPA

SNV

Missense_Mutation

novel

c.637A>C

p.Lys213Gln

p.K213Q

P23025

protein_coding

tolerated(0.38)

benign(0.107)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

XPA

SNV

Missense_Mutation

c.193N>A

p.Ala65Thr

p.A65T

P23025

protein_coding

tolerated(0.78)

benign(0)

TCGA-G4-6628-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

XPA

SNV

Missense_Mutation

novel

c.514N>T

p.His172Tyr

p.H172Y

P23025

protein_coding

tolerated(0.06)

benign(0.023)

TCGA-A5-A2K5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

XPA

SNV

Missense_Mutation

c.779N>A

p.Thr260Asn

p.T260N

P23025

protein_coding

deleterious(0.03)

benign(0.143)

TCGA-AJ-A3EK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

XPA

SNV

Missense_Mutation

novel

c.566N>T

p.Arg189Met

p.R189M

P23025

protein_coding

deleterious(0)

probably_damaging(0.924)

TCGA-AP-A05O-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

carboplatin

XPA

SNV

Missense_Mutation

c.725N>T

p.His242Leu

p.H242L

P23025

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-AX-A05S-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unspecific

Carboplatin & Paclitaxel

XPA

SNV

Missense_Mutation

c.484N>G

p.Leu162Val

p.L162V

P23025

protein_coding

deleterious(0.04)

benign(0.277)

TCGA-AX-A1C8-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unspecific

Carboplatin

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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
7507	XPA	CLINICALLY ACTIONABLE, DNA REPAIR		Platinum compounds		25069034
7507	XPA	CLINICALLY ACTIONABLE, DNA REPAIR		IMMUNOSUPPRESSIVE		11313422

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