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: FLRT3

Gene summary for FLRT3

Gene summary.

Gene information	Species	Human
	Gene symbol	FLRT3
	Gene ID	23767
	Gene name	fibronectin leucine rich transmembrane protein 3
	Gene Alias	HH21
	Cytomap	20p12.1
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	Q9NZU0

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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
23767	FLRT3	GSM5353237_PA_PR5251_T2_S8_L001	Human	Prostate	Tumor	1.86e-07	9.01e-01	0.1622
23767	FLRT3	GSM5353240_PA_PR5254_T1_S15_L001	Human	Prostate	Tumor	1.51e-02	3.52e-01	0.1575
23767	FLRT3	GSM5353243_PA_PR5261_T1_S23_L002	Human	Prostate	Tumor	3.10e-09	2.77e-01	0.1545
23767	FLRT3	GSM5353244_PA_PR5261_T2_S24_L002	Human	Prostate	Tumor	2.06e-03	2.13e-01	0.1569
23767	FLRT3	GSM5353247_PA_PR5269_3_S27_L002	Human	Prostate	Tumor	1.38e-02	5.59e-01	0.1532
23767	FLRT3	male-WTA	Human	Thyroid	PTC	1.30e-18	1.58e-01	0.1037
23767	FLRT3	PTC01	Human	Thyroid	PTC	1.98e-11	3.57e-01	0.1899
23767	FLRT3	PTC04	Human	Thyroid	PTC	1.94e-16	8.18e-01	0.1927
23767	FLRT3	PTC06	Human	Thyroid	PTC	1.78e-26	1.11e+00	0.2057
23767	FLRT3	PTC07	Human	Thyroid	PTC	1.49e-43	9.90e-01	0.2044
23767	FLRT3	ATC5	Human	Thyroid	ATC	9.28e-05	-8.67e-02	0.34

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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:0016049110	Esophagus	ESCC	cell growth	289/8552	482/18723	1.29e-10	3.77e-09	289
GO:00020115	Esophagus	ESCC	morphogenesis of an epithelial sheet	42/8552	57/18723	1.62e-05	1.45e-04	42
GO:006156415	Esophagus	ESCC	axon development	251/8552	467/18723	2.41e-04	1.49e-03	251
GO:003432918	Esophagus	ESCC	cell junction assembly	227/8552	420/18723	3.06e-04	1.83e-03	227
GO:00519606	Esophagus	ESCC	regulation of nervous system development	237/8552	443/18723	5.02e-04	2.78e-03	237
GO:006056010	Esophagus	ESCC	developmental growth involved in morphogenesis	131/8552	234/18723	9.28e-04	4.73e-03	131
GO:00519625	Esophagus	ESCC	positive regulation of nervous system development	149/8552	272/18723	1.50e-03	7.06e-03	149
GO:00486785	Esophagus	ESCC	response to axon injury	51/8552	83/18723	2.74e-03	1.16e-02	51
GO:000740915	Esophagus	ESCC	axonogenesis	219/8552	418/18723	3.14e-03	1.31e-02	219
GO:004858810	Esophagus	ESCC	developmental cell growth	125/8552	234/18723	1.01e-02	3.46e-02	125
GO:190188810	Esophagus	ESCC	regulation of cell junction assembly	109/8552	204/18723	1.53e-02	4.96e-02	109
GO:001604911	Liver	Cirrhotic	cell growth	160/4634	482/18723	1.50e-05	2.07e-04	160
GO:001604921	Liver	HCC	cell growth	269/7958	482/18723	1.84e-09	5.35e-08	269
GO:006056011	Liver	HCC	developmental growth involved in morphogenesis	124/7958	234/18723	7.37e-04	4.47e-03	124
GO:199013811	Liver	HCC	neuron projection extension	92/7958	172/18723	2.31e-03	1.14e-02	92
GO:004858811	Liver	HCC	developmental cell growth	121/7958	234/18723	2.68e-03	1.28e-02	121
GO:001604917	Oral cavity	OSCC	cell growth	268/7305	482/18723	6.55e-14	3.51e-12	268
GO:00020114	Oral cavity	OSCC	morphogenesis of an epithelial sheet	37/7305	57/18723	6.66e-05	5.38e-04	37
GO:00519624	Oral cavity	OSCC	positive regulation of nervous system development	135/7305	272/18723	2.20e-04	1.44e-03	135
GO:00485889	Oral cavity	OSCC	developmental cell growth	116/7305	234/18723	6.20e-04	3.50e-03	116

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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

FLRT3

SNV

Missense_Mutation

rs760038366

c.1514N>A

p.Arg505Gln

p.R505Q

Q9NZU0

protein_coding

tolerated(0.61)

benign(0)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FLRT3

SNV

Missense_Mutation

c.557G>A

p.Arg186His

p.R186H

Q9NZU0

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-BH-A0HA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

FLRT3

SNV

Missense_Mutation

c.1783N>A

p.Gln595Lys

p.Q595K

Q9NZU0

protein_coding

deleterious(0.01)

possibly_damaging(0.834)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FLRT3

SNV

Missense_Mutation

c.700C>T

p.Arg234Trp

p.R234W

Q9NZU0

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-E9-A243-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

FLRT3

SNV

Missense_Mutation

rs751955471

c.701N>A

p.Arg234Gln

p.R234Q

Q9NZU0

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-EW-A1P4-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

FLRT3

insertion

Frame_Shift_Ins

novel

c.1261_1262insGA

p.Asp421GlyfsTer14

p.D421Gfs*14

Q9NZU0

protein_coding

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FLRT3

SNV

Missense_Mutation

rs564318429

c.781N>T

p.Arg261Trp

p.R261W

Q9NZU0

protein_coding

deleterious(0.01)

possibly_damaging(0.697)

TCGA-C5-A2LV-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

FLRT3

SNV

Missense_Mutation

c.1100C>A

p.Thr367Asn

p.T367N

Q9NZU0

protein_coding

tolerated(0.17)

benign(0.147)

TCGA-EX-A69M-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

FLRT3

SNV

Missense_Mutation

rs537766361

c.488G>A

p.Arg163His

p.R163H

Q9NZU0

protein_coding

deleterious(0)

probably_damaging(0.985)

TCGA-VS-A8EH-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

FLRT3

SNV

Missense_Mutation

rs142379846

c.10N>A

p.Ala4Thr

p.A4T

Q9NZU0

protein_coding

tolerated_low_confidence(0.56)

benign(0)

TCGA-AA-3715-01

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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