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: SPIRE2

Gene summary for SPIRE2

Gene summary.

Gene information	Species	Human
	Gene symbol	SPIRE2
	Gene ID	84501
	Gene name	spire type actin nucleation factor 2
	Gene Alias	Spir-2
	Cytomap	16q24.3
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q8WWL2

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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
84501	SPIRE2	HCC1_Meng	Human	Liver	HCC	2.70e-16	5.44e-03	0.0246
84501	SPIRE2	HCC2_Meng	Human	Liver	HCC	4.25e-06	7.31e-02	0.0107
84501	SPIRE2	HCC1	Human	Liver	HCC	8.63e-19	2.33e+00	0.5336
84501	SPIRE2	HCC2	Human	Liver	HCC	2.45e-32	2.93e+00	0.5341
84501	SPIRE2	HCC5	Human	Liver	HCC	3.69e-40	2.17e+00	0.4932
84501	SPIRE2	S014	Human	Liver	HCC	4.21e-12	5.13e-01	0.2254
84501	SPIRE2	S015	Human	Liver	HCC	2.17e-07	3.81e-01	0.2375
84501	SPIRE2	S016	Human	Liver	HCC	5.06e-14	4.19e-01	0.2243
84501	SPIRE2	S027	Human	Liver	HCC	9.94e-05	4.44e-01	0.2446
84501	SPIRE2	S028	Human	Liver	HCC	1.56e-13	4.28e-01	0.2503
84501	SPIRE2	S029	Human	Liver	HCC	6.01e-11	3.84e-01	0.2581

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
Liver		NAFLD: Non-alcoholic fatty liver disease

∗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:004819321	Liver	HCC	Golgi vesicle transport	217/7958	296/18723	2.58e-27	1.02e-24	217
GO:004325422	Liver	HCC	regulation of protein-containing complex assembly	264/7958	428/18723	5.47e-16	4.39e-14	264
GO:005125822	Liver	HCC	protein polymerization	182/7958	297/18723	4.17e-11	1.58e-09	182
GO:003133412	Liver	HCC	positive regulation of protein-containing complex assembly	150/7958	237/18723	7.35e-11	2.63e-09	150
GO:190290322	Liver	HCC	regulation of supramolecular fiber organization	224/7958	383/18723	1.54e-10	5.33e-09	224
GO:000701522	Liver	HCC	actin filament organization	252/7958	442/18723	3.83e-10	1.25e-08	252
GO:005165621	Liver	HCC	establishment of organelle localization	226/7958	390/18723	4.15e-10	1.34e-08	226
GO:190290522	Liver	HCC	positive regulation of supramolecular fiber organization	131/7958	209/18723	2.85e-09	7.69e-08	131
GO:005149522	Liver	HCC	positive regulation of cytoskeleton organization	138/7958	226/18723	1.26e-08	3.12e-07	138
GO:003253522	Liver	HCC	regulation of cellular component size	217/7958	383/18723	1.28e-08	3.14e-07	217
GO:003227122	Liver	HCC	regulation of protein polymerization	141/7958	233/18723	2.00e-08	4.72e-07	141
GO:003297022	Liver	HCC	regulation of actin filament-based process	222/7958	397/18723	3.81e-08	8.30e-07	222
GO:003227322	Liver	HCC	positive regulation of protein polymerization	90/7958	138/18723	5.73e-08	1.21e-06	90
GO:003295622	Liver	HCC	regulation of actin cytoskeleton organization	202/7958	358/18723	6.18e-08	1.29e-06	202
GO:000815422	Liver	HCC	actin polymerization or depolymerization	130/7958	218/18723	2.31e-07	4.14e-06	130
GO:003004122	Liver	HCC	actin filament polymerization	116/7958	191/18723	2.66e-07	4.68e-06	116
GO:003250611	Liver	HCC	cytokinetic process	32/7958	39/18723	4.73e-07	7.69e-06	32
GO:005105221	Liver	HCC	regulation of DNA metabolic process	198/7958	359/18723	7.62e-07	1.17e-05	198
GO:011005322	Liver	HCC	regulation of actin filament organization	158/7958	278/18723	9.01e-07	1.37e-05	158
GO:003083212	Liver	HCC	regulation of actin filament length	113/7958	189/18723	1.16e-06	1.71e-05	113

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

SPIRE2

SNV

Missense_Mutation

rs138861470

c.1286C>T

p.Pro429Leu

p.P429L

Q8WWL2

protein_coding

deleterious(0.03)

probably_damaging(0.966)

TCGA-E2-A574-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SPIRE2

insertion

Nonsense_Mutation

novel

c.1862_1863insTCCATGTTAAATGTTGATTATGTGCAGGGTAAGGTG

p.Glu621delinsAspProCysTerMetLeuIleMetCysArgValArgTrp

p.E621delinsDPC*MLIMCRVRW

Q8WWL2

protein_coding

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

SPIRE2

deletion

Frame_Shift_Del

c.1212_1216delNNNNN

p.Pro405ArgfsTer10

p.P405Rfs*10

Q8WWL2

protein_coding

TCGA-BH-A1F6-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

SPIRE2

SNV

Missense_Mutation

c.910C>T

p.Pro304Ser

p.P304S

Q8WWL2

protein_coding

deleterious(0)

benign(0.046)

TCGA-EK-A2PG-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

SPIRE2

SNV

Missense_Mutation

rs146263316

c.1748N>T

p.Ser583Leu

p.S583L

Q8WWL2

protein_coding

deleterious(0)

probably_damaging(0.938)

TCGA-EX-A69L-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SPIRE2

SNV

Missense_Mutation

c.1050N>G

p.Ile350Met

p.I350M

Q8WWL2

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-IR-A3LK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

SPIRE2

SNV

Missense_Mutation

c.1921C>G

p.Gln641Glu

p.Q641E

Q8WWL2

protein_coding

tolerated(0.23)

benign(0.233)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SPIRE2

SNV

Missense_Mutation

c.1738N>T

p.Pro580Ser

p.P580S

Q8WWL2

protein_coding

tolerated(1)

benign(0.044)

TCGA-3L-AA1B-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

SPIRE2

SNV

Missense_Mutation

rs373707880

c.1100N>A

p.Arg367His

p.R367H

Q8WWL2

protein_coding

deleterious(0.05)

probably_damaging(0.994)

TCGA-A6-2686-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

SPIRE2

SNV

Missense_Mutation

c.2035N>A

p.Val679Met

p.V679M

Q8WWL2

protein_coding

deleterious(0)

probably_damaging(0.988)

TCGA-CA-6715-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

oxaliplatin

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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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