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:00601478	Oral cavity	OSCC	regulation of posttranscriptional gene silencing	31/7305	52/18723	2.08e-03	9.59e-03	31
GO:00342495	Oral cavity	OSCC	negative regulation of cellular amide metabolic process	130/7305	273/18723	2.20e-03	1.00e-02	130
GO:00171485	Oral cavity	OSCC	negative regulation of translation	113/7305	245/18723	1.34e-02	4.45e-02	113
GO:190331124	Oral cavity	EOLP	regulation of mRNA metabolic process	102/2218	288/18723	8.13e-26	2.44e-22	102
GO:004348426	Oral cavity	EOLP	regulation of RNA splicing	59/2218	148/18723	2.64e-18	5.27e-15	59
GO:000838025	Oral cavity	EOLP	RNA splicing	115/2218	434/18723	2.24e-17	3.04e-14	115
GO:005068424	Oral cavity	EOLP	regulation of mRNA processing	55/2218	137/18723	2.54e-17	3.04e-14	55
GO:000640224	Oral cavity	EOLP	mRNA catabolic process	74/2218	232/18723	3.36e-16	2.51e-13	74
GO:004802425	Oral cavity	EOLP	regulation of mRNA splicing, via spliceosome	42/2218	101/18723	3.41e-14	1.28e-11	42
GO:006101323	Oral cavity	EOLP	regulation of mRNA catabolic process	55/2218	166/18723	3.70e-13	1.11e-10	55
GO:000640124	Oral cavity	EOLP	RNA catabolic process	77/2218	278/18723	3.92e-13	1.12e-10	77
GO:000641726	Oral cavity	EOLP	regulation of translation	108/2218	468/18723	4.04e-12	7.34e-10	108
GO:004348823	Oral cavity	EOLP	regulation of mRNA stability	50/2218	158/18723	2.91e-11	4.15e-09	50
GO:000037725	Oral cavity	EOLP	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	80/2218	320/18723	4.20e-11	5.60e-09	80
GO:000039825	Oral cavity	EOLP	mRNA splicing, via spliceosome	80/2218	320/18723	4.20e-11	5.60e-09	80
GO:000037525	Oral cavity	EOLP	RNA splicing, via transesterification reactions	80/2218	324/18723	8.11e-11	9.53e-09	80
GO:004348723	Oral cavity	EOLP	regulation of RNA stability	51/2218	170/18723	1.63e-10	1.68e-08	51
GO:000038024	Oral cavity	EOLP	alternative mRNA splicing, via spliceosome	30/2218	77/18723	1.02e-09	7.13e-08	30
GO:003425024	Oral cavity	EOLP	positive regulation of cellular amide metabolic process	47/2218	162/18723	2.84e-09	1.77e-07	47
GO:003465523	Oral cavity	EOLP	nucleobase-containing compound catabolic process	89/2218	407/18723	5.47e-09	2.92e-07	89

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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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