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: FBXL12

Gene summary for FBXL12

Gene summary.

Gene information	Species	Human
	Gene symbol	FBXL12
	Gene ID	54850
	Gene name	F-box and leucine rich repeat protein 12
	Gene Alias	Fbl12
	Cytomap	19p13.2
	Gene Type	protein-coding
	GO ID	GO:0000086
	UniProtAcc	Q9NXK8

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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
54850	FBXL12	P54T-E	Human	Esophagus	ESCC	1.86e-25	5.53e-01	0.0975
54850	FBXL12	P56T-E	Human	Esophagus	ESCC	1.57e-02	4.88e-01	0.1613
54850	FBXL12	P57T-E	Human	Esophagus	ESCC	7.07e-14	2.35e-01	0.0926
54850	FBXL12	P61T-E	Human	Esophagus	ESCC	3.18e-22	6.54e-01	0.099
54850	FBXL12	P62T-E	Human	Esophagus	ESCC	8.12e-45	9.60e-01	0.1302
54850	FBXL12	P65T-E	Human	Esophagus	ESCC	5.30e-12	3.03e-01	0.0978
54850	FBXL12	P74T-E	Human	Esophagus	ESCC	5.46e-18	5.43e-01	0.1479
54850	FBXL12	P75T-E	Human	Esophagus	ESCC	4.65e-46	8.18e-01	0.1125
54850	FBXL12	P76T-E	Human	Esophagus	ESCC	6.08e-11	2.37e-01	0.1207
54850	FBXL12	P79T-E	Human	Esophagus	ESCC	2.77e-29	4.56e-01	0.1154
54850	FBXL12	P80T-E	Human	Esophagus	ESCC	1.28e-30	1.01e+00	0.155
54850	FBXL12	P82T-E	Human	Esophagus	ESCC	1.91e-12	4.06e-01	0.1072
54850	FBXL12	P83T-E	Human	Esophagus	ESCC	4.91e-26	7.39e-01	0.1738
54850	FBXL12	P84T-E	Human	Esophagus	ESCC	4.02e-05	4.14e-01	0.0933
54850	FBXL12	P89T-E	Human	Esophagus	ESCC	1.10e-13	5.26e-01	0.1752
54850	FBXL12	P91T-E	Human	Esophagus	ESCC	5.37e-13	1.04e+00	0.1828
54850	FBXL12	P107T-E	Human	Esophagus	ESCC	5.75e-34	7.36e-01	0.171
54850	FBXL12	P126T-E	Human	Esophagus	ESCC	6.37e-03	3.45e-01	0.1125
54850	FBXL12	P127T-E	Human	Esophagus	ESCC	1.06e-15	2.79e-01	0.0826
54850	FBXL12	P128T-E	Human	Esophagus	ESCC	2.03e-25	8.28e-01	0.1241

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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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:0010498	Colorectum	AD	proteasomal protein catabolic process	174/3918	490/18723	3.18e-14	7.66e-12	174
GO:0043161	Colorectum	AD	proteasome-mediated ubiquitin-dependent protein catabolic process	141/3918	412/18723	1.77e-10	1.68e-08	141
GO:0007623	Colorectum	AD	circadian rhythm	72/3918	210/18723	4.50e-06	1.21e-04	72
GO:0048511	Colorectum	AD	rhythmic process	94/3918	298/18723	1.00e-05	2.34e-04	94
GO:0042752	Colorectum	AD	regulation of circadian rhythm	40/3918	121/18723	1.24e-03	1.09e-02	40
GO:00104982	Colorectum	MSS	proteasomal protein catabolic process	157/3467	490/18723	2.39e-13	5.25e-11	157
GO:00431612	Colorectum	MSS	proteasome-mediated ubiquitin-dependent protein catabolic process	127/3467	412/18723	7.70e-10	6.32e-08	127
GO:00076232	Colorectum	MSS	circadian rhythm	69/3467	210/18723	4.22e-07	1.67e-05	69
GO:00485112	Colorectum	MSS	rhythmic process	89/3467	298/18723	1.17e-06	3.96e-05	89
GO:00427522	Colorectum	MSS	regulation of circadian rhythm	38/3467	121/18723	4.33e-04	5.23e-03	38
GO:0010498111	Esophagus	ESCC	proteasomal protein catabolic process	369/8552	490/18723	1.13e-41	1.80e-38	369
GO:0043161111	Esophagus	ESCC	proteasome-mediated ubiquitin-dependent protein catabolic process	312/8552	412/18723	3.53e-36	4.48e-33	312
GO:004477216	Esophagus	ESCC	mitotic cell cycle phase transition	281/8552	424/18723	4.63e-18	4.45e-16	281
GO:000931419	Esophagus	ESCC	response to radiation	277/8552	456/18723	4.42e-11	1.43e-09	277
GO:00448394	Esophagus	ESCC	cell cycle G2/M phase transition	103/8552	148/18723	3.09e-09	6.67e-08	103
GO:00000864	Esophagus	ESCC	G2/M transition of mitotic cell cycle	96/8552	137/18723	6.00e-09	1.23e-07	96
GO:000941611	Esophagus	ESCC	response to light stimulus	183/8552	320/18723	2.03e-05	1.76e-04	183
GO:004851118	Esophagus	ESCC	rhythmic process	164/8552	298/18723	6.80e-04	3.57e-03	164
GO:000762319	Esophagus	ESCC	circadian rhythm	119/8552	210/18723	8.47e-04	4.36e-03	119
GO:00311461	Esophagus	ESCC	SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	33/8552	49/18723	1.80e-03	8.26e-03	33

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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

FBXL12

SNV

Missense_Mutation

novel

c.722N>G

p.Ser241Cys

p.S241C

Q9NXK8

protein_coding

deleterious(0)

benign(0.021)

TCGA-AC-A6IW-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FBXL12

SNV

Missense_Mutation

novel

c.908T>G

p.Leu303Arg

p.L303R

Q9NXK8

protein_coding

tolerated(0.62)

possibly_damaging(0.634)

TCGA-AA-3663-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

FBXL12

SNV

Missense_Mutation

novel

c.300G>T

p.Lys100Asn

p.K100N

Q9NXK8

protein_coding

deleterious(0.01)

possibly_damaging(0.535)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

FBXL12

SNV

Missense_Mutation

novel

c.529G>C

p.Ala177Pro

p.A177P

Q9NXK8

protein_coding

tolerated(0.22)

possibly_damaging(0.55)

TCGA-AJ-A3EK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

FBXL12

SNV

Missense_Mutation

novel

c.671N>T

p.Ser224Ile

p.S224I

Q9NXK8

protein_coding

deleterious(0.01)

benign(0.307)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

FBXL12

SNV

Missense_Mutation

novel

c.284G>T

p.Arg95Ile

p.R95I

Q9NXK8

protein_coding

tolerated(0.08)

benign(0.138)

TCGA-AX-A1CE-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

FBXL12

SNV

Missense_Mutation

rs138149906

c.317N>A

p.Arg106His

p.R106H

Q9NXK8

protein_coding

tolerated(0.33)

benign(0.003)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

FBXL12

SNV

Missense_Mutation

novel

c.362G>A

p.Ser121Asn

p.S121N

Q9NXK8

protein_coding

tolerated(0.31)

benign(0.263)

TCGA-B5-A3FA-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

FBXL12

SNV

Missense_Mutation

rs375844904

c.683N>A

p.Arg228Gln

p.R228Q

Q9NXK8

protein_coding

tolerated(0.06)

benign(0.012)

TCGA-BG-A222-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

FBXL12

SNV

Missense_Mutation

novel

c.243C>A

p.Phe81Leu

p.F81L

Q9NXK8

protein_coding

tolerated(0.69)

benign(0)

TCGA-BS-A0UF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=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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