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: FXR1

Gene summary for FXR1

Gene summary.

Gene information	Species	Human
	Gene symbol	FXR1
	Gene ID	8087
	Gene name	FMR1 autosomal homolog 1
	Gene Alias	FXR1P
	Cytomap	3q26.33
	Gene Type	protein-coding
	GO ID	GO:0000375
	UniProtAcc	P51114

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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
8087	FXR1	LZE2T	Human	Esophagus	ESCC	1.92e-06	1.61e+00	0.082
8087	FXR1	LZE4T	Human	Esophagus	ESCC	2.34e-36	1.39e+00	0.0811
8087	FXR1	LZE7T	Human	Esophagus	ESCC	3.66e-08	8.70e-01	0.0667
8087	FXR1	LZE8T	Human	Esophagus	ESCC	7.71e-11	4.14e-01	0.067
8087	FXR1	LZE20T	Human	Esophagus	ESCC	1.69e-11	3.42e-01	0.0662
8087	FXR1	LZE22D1	Human	Esophagus	HGIN	9.92e-06	9.40e-02	0.0595
8087	FXR1	LZE22T	Human	Esophagus	ESCC	5.04e-03	6.67e-01	0.068
8087	FXR1	LZE24T	Human	Esophagus	ESCC	9.08e-24	1.07e+00	0.0596
8087	FXR1	LZE21T	Human	Esophagus	ESCC	2.03e-10	1.28e+00	0.0655
8087	FXR1	LZE6T	Human	Esophagus	ESCC	7.85e-04	7.11e-01	0.0845
8087	FXR1	P1T-E	Human	Esophagus	ESCC	2.92e-06	9.35e-01	0.0875
8087	FXR1	P2T-E	Human	Esophagus	ESCC	2.82e-89	1.97e+00	0.1177
8087	FXR1	P4T-E	Human	Esophagus	ESCC	2.33e-58	1.52e+00	0.1323
8087	FXR1	P5T-E	Human	Esophagus	ESCC	4.16e-62	1.59e+00	0.1327
8087	FXR1	P8T-E	Human	Esophagus	ESCC	1.70e-34	9.88e-01	0.0889
8087	FXR1	P9T-E	Human	Esophagus	ESCC	2.54e-34	1.03e+00	0.1131
8087	FXR1	P10T-E	Human	Esophagus	ESCC	1.34e-58	1.23e+00	0.116
8087	FXR1	P11T-E	Human	Esophagus	ESCC	2.04e-24	1.35e+00	0.1426
8087	FXR1	P12T-E	Human	Esophagus	ESCC	3.37e-81	2.19e+00	0.1122
8087	FXR1	P15T-E	Human	Esophagus	ESCC	6.40e-68	2.00e+00	0.1149

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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
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:000838026	Esophagus	HGIN	RNA splicing	160/2587	434/18723	3.74e-34	1.12e-30	160
GO:000037520	Esophagus	HGIN	RNA splicing, via transesterification reactions	115/2587	324/18723	3.16e-23	3.80e-20	115
GO:000037720	Esophagus	HGIN	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	113/2587	320/18723	1.24e-22	9.26e-20	113
GO:000039820	Esophagus	HGIN	mRNA splicing, via spliceosome	113/2587	320/18723	1.24e-22	9.26e-20	113
GO:000641727	Esophagus	HGIN	regulation of translation	139/2587	468/18723	1.46e-19	7.98e-17	139
GO:004348427	Esophagus	HGIN	regulation of RNA splicing	59/2587	148/18723	3.61e-15	7.22e-13	59
GO:190331120	Esophagus	HGIN	regulation of mRNA metabolic process	91/2587	288/18723	5.06e-15	9.78e-13	91
GO:005068419	Esophagus	HGIN	regulation of mRNA processing	55/2587	137/18723	2.17e-14	3.94e-12	55
GO:004802426	Esophagus	HGIN	regulation of mRNA splicing, via spliceosome	42/2587	101/18723	6.35e-12	7.78e-10	42
GO:004572720	Esophagus	HGIN	positive regulation of translation	49/2587	136/18723	5.88e-11	6.30e-09	49
GO:003425020	Esophagus	HGIN	positive regulation of cellular amide metabolic process	53/2587	162/18723	6.01e-10	5.15e-08	53
GO:000640120	Esophagus	HGIN	RNA catabolic process	77/2587	278/18723	7.63e-10	6.36e-08	77
GO:000640220	Esophagus	HGIN	mRNA catabolic process	67/2587	232/18723	1.47e-09	1.13e-07	67
GO:000038018	Esophagus	HGIN	alternative mRNA splicing, via spliceosome	32/2587	77/18723	2.06e-09	1.54e-07	32
GO:003465519	Esophagus	HGIN	nucleobase-containing compound catabolic process	98/2587	407/18723	1.44e-08	8.94e-07	98
GO:004670017	Esophagus	HGIN	heterocycle catabolic process	103/2587	445/18723	5.44e-08	2.99e-06	103
GO:004427018	Esophagus	HGIN	cellular nitrogen compound catabolic process	103/2587	451/18723	1.10e-07	5.56e-06	103
GO:001943917	Esophagus	HGIN	aromatic compound catabolic process	105/2587	467/18723	1.89e-07	9.31e-06	105
GO:190136117	Esophagus	HGIN	organic cyclic compound catabolic process	106/2587	495/18723	1.94e-06	7.13e-05	106
GO:00342496	Esophagus	HGIN	negative regulation of cellular amide metabolic process	66/2587	273/18723	2.74e-06	9.60e-05	66

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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

FXR1

SNV

Missense_Mutation

c.1837N>C

p.Glu613Gln

p.E613Q

P51114

protein_coding

tolerated_low_confidence(0.55)

benign(0.043)

TCGA-A2-A0CX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

FXR1

SNV

Missense_Mutation

c.1628N>A

p.Arg543Lys

p.R543K

P51114

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.899)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FXR1

SNV

Missense_Mutation

c.916N>C

p.Glu306Gln

p.E306Q

P51114

protein_coding

deleterious(0)

probably_damaging(0.98)

TCGA-AO-A0J6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

FXR1

SNV

Missense_Mutation

rs755691527

c.786N>A

p.Phe262Leu

p.F262L

P51114

protein_coding

deleterious(0.01)

probably_damaging(0.966)

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FXR1

SNV

Missense_Mutation

c.1094N>C

p.Arg365Thr

p.R365T

P51114

protein_coding

tolerated(0.06)

benign(0.432)

TCGA-E9-A1N4-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

FXR1

SNV

Missense_Mutation

novel

c.754G>A

p.Ala252Thr

p.A252T

P51114

protein_coding

tolerated(0.12)

benign(0.003)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

FXR1

SNV

Missense_Mutation

rs371485992

c.1298G>A

p.Arg433Gln

p.R433Q

P51114

protein_coding

tolerated(0.22)

probably_damaging(0.968)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

FXR1

SNV

Missense_Mutation

rs751470533

c.1765G>A

p.Asp589Asn

p.D589N

P51114

protein_coding

deleterious_low_confidence(0.04)

benign(0.001)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

FXR1

SNV

Missense_Mutation

c.298N>C

p.Asp100His

p.D100H

P51114

protein_coding

deleterious(0)

possibly_damaging(0.813)

TCGA-C5-A1M5-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

FXR1

SNV

Missense_Mutation

c.411N>C

p.Leu137Phe

p.L137F

P51114

protein_coding

deleterious(0)

probably_damaging(0.991)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

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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