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: UPF1

Gene summary for UPF1

Gene summary.

Gene information	Species	Human
	Gene symbol	UPF1
	Gene ID	5976
	Gene name	UPF1 RNA helicase and ATPase
	Gene Alias	HUPF1
	Cytomap	19p13.11
	Gene Type	protein-coding
	GO ID	GO:0000184
	UniProtAcc	A0A024R7L8

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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
5976	UPF1	LZE4T	Human	Esophagus	ESCC	1.95e-05	8.98e-05	0.0811
5976	UPF1	LZE5T	Human	Esophagus	ESCC	1.49e-05	3.97e-01	0.0514
5976	UPF1	LZE7T	Human	Esophagus	ESCC	6.01e-12	8.16e-01	0.0667
5976	UPF1	LZE8T	Human	Esophagus	ESCC	9.27e-07	3.68e-02	0.067
5976	UPF1	LZE20T	Human	Esophagus	ESCC	2.13e-04	5.57e-02	0.0662
5976	UPF1	LZE22T	Human	Esophagus	ESCC	1.38e-05	2.21e-01	0.068
5976	UPF1	LZE24T	Human	Esophagus	ESCC	7.47e-10	2.91e-01	0.0596
5976	UPF1	P1T-E	Human	Esophagus	ESCC	3.98e-06	2.73e-01	0.0875
5976	UPF1	P2T-E	Human	Esophagus	ESCC	2.95e-11	7.18e-02	0.1177
5976	UPF1	P4T-E	Human	Esophagus	ESCC	6.74e-15	2.39e-01	0.1323
5976	UPF1	P5T-E	Human	Esophagus	ESCC	1.93e-10	1.08e-01	0.1327
5976	UPF1	P8T-E	Human	Esophagus	ESCC	1.44e-18	4.90e-01	0.0889
5976	UPF1	P9T-E	Human	Esophagus	ESCC	9.64e-14	2.94e-01	0.1131
5976	UPF1	P10T-E	Human	Esophagus	ESCC	7.24e-16	3.78e-01	0.116
5976	UPF1	P12T-E	Human	Esophagus	ESCC	1.79e-13	1.67e-01	0.1122
5976	UPF1	P15T-E	Human	Esophagus	ESCC	1.02e-08	1.53e-01	0.1149
5976	UPF1	P16T-E	Human	Esophagus	ESCC	2.60e-12	-1.66e-02	0.1153
5976	UPF1	P17T-E	Human	Esophagus	ESCC	2.49e-04	1.12e-01	0.1278
5976	UPF1	P19T-E	Human	Esophagus	ESCC	3.21e-03	1.08e-01	0.1662
5976	UPF1	P20T-E	Human	Esophagus	ESCC	3.33e-09	1.11e-02	0.1124

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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:0006913110	Esophagus	ESCC	nucleocytoplasmic transport	230/8552	301/18723	6.04e-28	2.02e-25	230
GO:0051169110	Esophagus	ESCC	nuclear transport	230/8552	301/18723	6.04e-28	2.02e-25	230
GO:0006403110	Esophagus	ESCC	RNA localization	166/8552	201/18723	1.95e-27	6.18e-25	166
GO:0022411111	Esophagus	ESCC	cellular component disassembly	305/8552	443/18723	1.94e-23	4.57e-21	305
GO:0009896111	Esophagus	ESCC	positive regulation of catabolic process	332/8552	492/18723	4.36e-23	9.22e-21	332
GO:0031331111	Esophagus	ESCC	positive regulation of cellular catabolic process	292/8552	427/18723	8.67e-22	1.53e-19	292
GO:1903311110	Esophagus	ESCC	regulation of mRNA metabolic process	210/8552	288/18723	3.25e-21	5.56e-19	210
GO:0006401110	Esophagus	ESCC	RNA catabolic process	204/8552	278/18723	3.39e-21	5.66e-19	204
GO:005123617	Esophagus	ESCC	establishment of RNA localization	134/8552	166/18723	1.23e-20	1.81e-18	134
GO:0051168110	Esophagus	ESCC	nuclear export	126/8552	154/18723	1.88e-20	2.65e-18	126
GO:005102815	Esophagus	ESCC	mRNA transport	110/8552	130/18723	2.76e-20	3.80e-18	110
GO:005065717	Esophagus	ESCC	nucleic acid transport	131/8552	163/18723	6.94e-20	8.46e-18	131
GO:005065817	Esophagus	ESCC	RNA transport	131/8552	163/18723	6.94e-20	8.46e-18	131
GO:003304416	Esophagus	ESCC	regulation of chromosome organization	145/8552	187/18723	3.80e-19	4.31e-17	145
GO:0034655110	Esophagus	ESCC	nucleobase-containing compound catabolic process	272/8552	407/18723	2.92e-18	2.90e-16	272
GO:0006402110	Esophagus	ESCC	mRNA catabolic process	170/8552	232/18723	8.70e-18	8.00e-16	170
GO:0006417111	Esophagus	ESCC	regulation of translation	304/8552	468/18723	1.53e-17	1.33e-15	304
GO:001593117	Esophagus	ESCC	nucleobase-containing compound transport	162/8552	222/18723	9.87e-17	7.93e-15	162
GO:004670018	Esophagus	ESCC	heterocycle catabolic process	286/8552	445/18723	1.12e-15	7.47e-14	286
GO:004427019	Esophagus	ESCC	cellular nitrogen compound catabolic process	288/8552	451/18723	3.03e-15	1.79e-13	288

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0301321	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa0301524	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa0301331	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa0301534	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa03013	Liver	HCC	Nucleocytoplasmic transport	81/4020	108/8465	4.28e-09	6.83e-08	3.80e-08	81
hsa0301521	Liver	HCC	mRNA surveillance pathway	66/4020	97/8465	3.16e-05	1.88e-04	1.04e-04	66
hsa030131	Liver	HCC	Nucleocytoplasmic transport	81/4020	108/8465	4.28e-09	6.83e-08	3.80e-08	81
hsa0301531	Liver	HCC	mRNA surveillance pathway	66/4020	97/8465	3.16e-05	1.88e-04	1.04e-04	66
hsa030136	Oral cavity	OSCC	Nucleocytoplasmic transport	82/3704	108/8465	7.93e-12	1.33e-10	6.77e-11	82
hsa030158	Oral cavity	OSCC	mRNA surveillance pathway	75/3704	97/8465	1.30e-11	2.01e-10	1.02e-10	75
hsa0301311	Oral cavity	OSCC	Nucleocytoplasmic transport	82/3704	108/8465	7.93e-12	1.33e-10	6.77e-11	82
hsa0301513	Oral cavity	OSCC	mRNA surveillance pathway	75/3704	97/8465	1.30e-11	2.01e-10	1.02e-10	75
hsa030155	Prostate	BPH	mRNA surveillance pathway	32/1718	97/8465	2.20e-03	8.63e-03	5.34e-03	32
hsa0301512	Prostate	BPH	mRNA surveillance pathway	32/1718	97/8465	2.20e-03	8.63e-03	5.34e-03	32
hsa0301522	Prostate	Tumor	mRNA surveillance pathway	33/1791	97/8465	2.18e-03	8.60e-03	5.33e-03	33
hsa0301532	Prostate	Tumor	mRNA surveillance pathway	33/1791	97/8465	2.18e-03	8.60e-03	5.33e-03	33

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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

UPF1

SNV

Missense_Mutation

c.1319N>T

p.Thr440Met

p.T440M

Q92900

protein_coding

deleterious(0.01)

possibly_damaging(0.506)

TCGA-A2-A0CQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

UPF1

SNV

Missense_Mutation

c.719C>G

p.Ser240Cys

p.S240C

Q92900

protein_coding

deleterious(0.01)

probably_damaging(0.918)

TCGA-B6-A0I6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

UPF1

SNV

Missense_Mutation

c.1417N>T

p.Arg473Cys

p.R473C

Q92900

protein_coding

deleterious(0)

possibly_damaging(0.753)

TCGA-B6-A0RS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

UPF1

SNV

Missense_Mutation

c.1073N>C

p.Val358Ala

p.V358A

Q92900

protein_coding

tolerated_low_confidence(0.83)

benign(0)

TCGA-EW-A1PD-01

Breast

breast invasive carcinoma

Male

<65

I/II

Chemotherapy

docetaxel

UPF1

SNV

Missense_Mutation

novel

c.1835N>A

p.Thr612Asn

p.T612N

Q92900

protein_coding

tolerated(0.27)

benign(0.001)

TCGA-LL-A5YL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

UPF1

insertion

Nonsense_Mutation

novel

c.2983_2984insATGTATGATGCCCGGGAGGCCATCATCCCAGGCT

p.Pro995HisfsTer3

p.P995Hfs*3

Q92900

protein_coding

TCGA-A2-A0CP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

UPF1

insertion

Frame_Shift_Ins

novel

c.2707_2708insTCATCATCCTGTCCTGTGTGCGGGCC

p.Tyr903PhefsTer48

p.Y903Ffs*48

Q92900

protein_coding

TCGA-A7-A0D9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

UPF1

deletion

Frame_Shift_Del

novel

c.2442delN

p.Val815CysfsTer50

p.V815Cfs*50

Q92900

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

UPF1

SNV

Missense_Mutation

novel

c.2108N>A

p.Gly703Asp

p.G703D

Q92900

protein_coding

deleterious(0.02)

possibly_damaging(0.697)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

UPF1

SNV

Missense_Mutation

c.1201G>C

p.Glu401Gln

p.E401Q

Q92900

protein_coding

deleterious(0.01)

benign(0.293)

TCGA-C5-A2LY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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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