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:00062604	Esophagus	ESCC	DNA replication	181/8552	260/18723	3.55e-15	2.05e-13	181
GO:001943918	Esophagus	ESCC	aromatic compound catabolic process	295/8552	467/18723	1.09e-14	5.98e-13	295
GO:190136118	Esophagus	ESCC	organic cyclic compound catabolic process	307/8552	495/18723	9.99e-14	4.80e-12	307
GO:005105215	Esophagus	ESCC	regulation of DNA metabolic process	232/8552	359/18723	2.40e-13	1.13e-11	232
GO:007116612	Esophagus	ESCC	ribonucleoprotein complex localization	66/8552	77/18723	2.94e-13	1.38e-11	66
GO:007142612	Esophagus	ESCC	ribonucleoprotein complex export from nucleus	65/8552	76/18723	5.56e-13	2.50e-11	65
GO:000095618	Esophagus	ESCC	nuclear-transcribed mRNA catabolic process	88/8552	112/18723	9.41e-13	4.14e-11	88
GO:000072319	Esophagus	ESCC	telomere maintenance	99/8552	131/18723	2.68e-12	1.08e-10	99
GO:000640512	Esophagus	ESCC	RNA export from nucleus	68/8552	84/18723	2.99e-11	1.01e-09	68
GO:003298416	Esophagus	ESCC	protein-containing complex disassembly	151/8552	224/18723	3.45e-11	1.15e-09	151
GO:003220417	Esophagus	ESCC	regulation of telomere maintenance	65/8552	80/18723	6.02e-11	1.90e-09	65
GO:00064064	Esophagus	ESCC	mRNA export from nucleus	51/8552	59/18723	7.98e-11	2.47e-09	51
GO:00714274	Esophagus	ESCC	mRNA-containing ribonucleoprotein complex export from nucleus	51/8552	59/18723	7.98e-11	2.47e-09	51
GO:190331316	Esophagus	ESCC	positive regulation of mRNA metabolic process	87/8552	118/18723	5.10e-10	1.32e-08	87
GO:006101319	Esophagus	ESCC	regulation of mRNA catabolic process	115/8552	166/18723	5.90e-10	1.49e-08	115
GO:004348719	Esophagus	ESCC	regulation of RNA stability	117/8552	170/18723	7.91e-10	1.94e-08	117
GO:004348819	Esophagus	ESCC	regulation of mRNA stability	109/8552	158/18723	2.40e-09	5.35e-08	109
GO:003150314	Esophagus	ESCC	protein-containing complex localization	139/8552	220/18723	1.14e-07	1.85e-06	139
GO:00400295	Esophagus	ESCC	regulation of gene expression, epigenetic	74/8552	105/18723	2.24e-07	3.42e-06	74
GO:00062612	Esophagus	ESCC	DNA-dependent DNA replication	100/8552	151/18723	2.61e-07	3.94e-06	100

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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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