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: FRMD4B

Gene summary for FRMD4B

Gene summary.

Gene information	Species	Human
	Gene symbol	FRMD4B
	Gene ID	23150
	Gene name	FERM domain containing 4B
	Gene Alias	6030440G05Rik
	Cytomap	3p14.1
	Gene Type	protein-coding
	GO ID	GO:0007163
	UniProtAcc	B3KNA2

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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
23150	FRMD4B	LZE4T	Human	Esophagus	ESCC	3.80e-11	7.17e-01	0.0811
23150	FRMD4B	LZE5T	Human	Esophagus	ESCC	1.61e-02	9.53e-02	0.0514
23150	FRMD4B	LZE7T	Human	Esophagus	ESCC	6.26e-03	3.51e-01	0.0667
23150	FRMD4B	LZE8T	Human	Esophagus	ESCC	9.93e-04	7.32e-02	0.067
23150	FRMD4B	LZE24T	Human	Esophagus	ESCC	2.32e-02	3.21e-01	0.0596
23150	FRMD4B	P1T-E	Human	Esophagus	ESCC	1.03e-06	3.57e-01	0.0875
23150	FRMD4B	P2T-E	Human	Esophagus	ESCC	3.93e-27	5.81e-01	0.1177
23150	FRMD4B	P4T-E	Human	Esophagus	ESCC	1.23e-13	5.90e-01	0.1323
23150	FRMD4B	P5T-E	Human	Esophagus	ESCC	1.00e-10	3.07e-01	0.1327
23150	FRMD4B	P8T-E	Human	Esophagus	ESCC	1.81e-13	3.05e-01	0.0889
23150	FRMD4B	P9T-E	Human	Esophagus	ESCC	4.41e-12	5.08e-01	0.1131
23150	FRMD4B	P10T-E	Human	Esophagus	ESCC	8.32e-27	5.88e-01	0.116
23150	FRMD4B	P11T-E	Human	Esophagus	ESCC	8.22e-08	3.14e-01	0.1426
23150	FRMD4B	P12T-E	Human	Esophagus	ESCC	2.20e-36	7.43e-01	0.1122
23150	FRMD4B	P15T-E	Human	Esophagus	ESCC	5.72e-09	3.00e-01	0.1149
23150	FRMD4B	P16T-E	Human	Esophagus	ESCC	3.02e-16	1.45e-01	0.1153
23150	FRMD4B	P17T-E	Human	Esophagus	ESCC	3.30e-03	2.57e-01	0.1278
23150	FRMD4B	P20T-E	Human	Esophagus	ESCC	9.10e-04	8.93e-02	0.1124
23150	FRMD4B	P21T-E	Human	Esophagus	ESCC	1.88e-10	3.19e-01	0.1617
23150	FRMD4B	P22T-E	Human	Esophagus	ESCC	4.48e-19	-2.31e-02	0.1236

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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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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
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:000716320	Esophagus	ESCC	establishment or maintenance of cell polarity	143/8552	218/18723	2.05e-09	4.65e-08	143
GO:003001018	Esophagus	ESCC	establishment of cell polarity	96/8552	143/18723	1.69e-07	2.67e-06	96
GO:009016216	Esophagus	ESCC	establishment of epithelial cell polarity	25/8552	31/18723	7.13e-05	5.38e-04	25
GO:000716312	Liver	Cirrhotic	establishment or maintenance of cell polarity	82/4634	218/18723	1.55e-05	2.11e-04	82
GO:00901625	Liver	Cirrhotic	establishment of epithelial cell polarity	14/4634	31/18723	1.05e-02	4.65e-02	14
GO:003001012	Liver	Cirrhotic	establishment of cell polarity	48/4634	143/18723	1.09e-02	4.79e-02	48
GO:000716322	Liver	HCC	establishment or maintenance of cell polarity	133/7958	218/18723	2.48e-08	5.73e-07	133
GO:003001022	Liver	HCC	establishment of cell polarity	82/7958	143/18723	2.38e-04	1.79e-03	82
GO:00071637	Lung	IAC	establishment or maintenance of cell polarity	61/2061	218/18723	3.10e-12	3.07e-09	61
GO:00300107	Lung	IAC	establishment of cell polarity	46/2061	143/18723	7.70e-12	4.27e-09	46
GO:00901626	Lung	IAC	establishment of epithelial cell polarity	11/2061	31/18723	2.91e-04	4.72e-03	11
GO:000716313	Lung	AIS	establishment or maintenance of cell polarity	56/1849	218/18723	1.31e-11	6.13e-09	56
GO:003001013	Lung	AIS	establishment of cell polarity	42/1849	143/18723	5.03e-11	1.95e-08	42
GO:009016212	Lung	AIS	establishment of epithelial cell polarity	11/1849	31/18723	1.10e-04	2.57e-03	11
GO:000716323	Lung	AAH	establishment or maintenance of cell polarity	24/613	218/18723	2.21e-07	1.01e-04	24
GO:003001023	Lung	AAH	establishment of cell polarity	17/613	143/18723	4.53e-06	1.22e-03	17
GO:009016222	Lung	AAH	establishment of epithelial cell polarity	6/613	31/18723	4.40e-04	1.92e-02	6
GO:003001031	Lung	MIAC	establishment of cell polarity	27/967	143/18723	4.16e-09	4.27e-06	27
GO:000716332	Lung	MIAC	establishment or maintenance of cell polarity	34/967	218/18723	7.70e-09	4.94e-06	34
GO:009016231	Lung	MIAC	establishment of epithelial cell polarity	7/967	31/18723	8.47e-04	1.83e-02	7

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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

FRMD4B

SNV

Missense_Mutation

novel

c.1336G>A

p.Glu446Lys

p.E446K

Q9Y2L6

protein_coding

tolerated(0.19)

benign(0.318)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

FRMD4B

SNV

Missense_Mutation

novel

c.3027N>A

p.Asn1009Lys

p.N1009K

Q9Y2L6

protein_coding

tolerated_low_confidence(0.25)

benign(0.006)

TCGA-AC-A3YI-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cytoxan

FRMD4B

SNV

Missense_Mutation

c.2498A>G

p.Tyr833Cys

p.Y833C

Q9Y2L6

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-B6-A0IH-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

FRMD4B

SNV

Missense_Mutation

c.1456N>C

p.Lys486Gln

p.K486Q

Q9Y2L6

protein_coding

deleterious(0.02)

possibly_damaging(0.455)

TCGA-D8-A140-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin+cyclophosphamid

FRMD4B

SNV

Missense_Mutation

c.2550G>C

p.Gln850His

p.Q850H

Q9Y2L6

protein_coding

tolerated(0.54)

benign(0)

TCGA-EW-A1J5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

FRMD4B

insertion

Nonsense_Mutation

novel

c.2898_2899insAAAGAGAGAGCGATGAGATCTGATCTGCTATGACAGAATCAGTGTGGG

p.Ile966_Gly967insLysGluArgAlaMetArgSerAspLeuLeuTerGlnAsnGlnCysGly

p.I966_G967insKERAMRSDLL*QNQCG

Q9Y2L6

protein_coding

TCGA-3C-AAAU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

zoladex

FRMD4B

insertion

Frame_Shift_Ins

novel

c.2175_2176insAACCCTTCCTACCGGTCCTCAGCCCACTATGGATATGAGCG

p.Leu726AsnfsTer32

p.L726Nfs*32

Q9Y2L6

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FRMD4B

insertion

Frame_Shift_Ins

novel

c.2771_2772insCCTGGGATTATGCA

p.Arg924SerfsTer46

p.R924Sfs*46

Q9Y2L6

protein_coding

TCGA-AN-A0FV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

FRMD4B

insertion

Nonsense_Mutation

novel

c.3000_3001insTAGGCACTAACGTAACTGTAGGGTCTGCCCACATGTTGAAGT

p.Ile1000_Ser1001insTer

p.I1000_S1001ins*

Q9Y2L6

protein_coding

TCGA-AN-A0FX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

FRMD4B

insertion

In_Frame_Ins

novel

c.1204_1205insGGAGTATGAGACCAGTAATGGCAGTAA

p.Ile401_Met402insArgSerMetArgProValMetAlaVal

p.I401_M402insRSMRPVMAV

Q9Y2L6

protein_coding

TCGA-E2-A1LL-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

docetaxel

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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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