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: RTF1

Gene summary for RTF1

Gene summary.

Gene information	Species	Human
	Gene symbol	RTF1
	Gene ID	23168
	Gene name	RTF1 homolog, Paf1/RNA polymerase II complex component
	Gene Alias	GTL7
	Cytomap	15q15.1
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	Q92541

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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
23168	RTF1	GSM4909286	Human	Breast	IDC	8.87e-03	5.98e-03	0.1081
23168	RTF1	GSM4909290	Human	Breast	IDC	5.85e-03	3.85e-01	0.2096
23168	RTF1	GSM4909293	Human	Breast	IDC	8.01e-07	2.02e-01	0.1581
23168	RTF1	GSM4909294	Human	Breast	IDC	6.35e-03	8.95e-02	0.2022
23168	RTF1	GSM4909296	Human	Breast	IDC	2.98e-06	-7.59e-02	0.1524
23168	RTF1	GSM4909297	Human	Breast	IDC	1.08e-11	-5.49e-02	0.1517
23168	RTF1	GSM4909301	Human	Breast	IDC	6.17e-22	5.52e-01	0.1577
23168	RTF1	GSM4909306	Human	Breast	IDC	2.37e-08	3.25e-01	0.1564
23168	RTF1	GSM4909307	Human	Breast	IDC	3.48e-04	2.59e-01	0.1569
23168	RTF1	GSM4909308	Human	Breast	IDC	3.02e-03	3.45e-01	0.158
23168	RTF1	GSM4909311	Human	Breast	IDC	2.07e-28	-2.38e-02	0.1534
23168	RTF1	GSM4909312	Human	Breast	IDC	2.81e-11	1.00e-01	0.1552
23168	RTF1	GSM4909313	Human	Breast	IDC	6.75e-03	2.16e-01	0.0391
23168	RTF1	GSM4909319	Human	Breast	IDC	1.01e-39	3.41e-02	0.1563
23168	RTF1	GSM4909320	Human	Breast	IDC	5.18e-05	2.30e-01	0.1575
23168	RTF1	GSM4909321	Human	Breast	IDC	8.17e-12	1.46e-01	0.1559
23168	RTF1	brca3	Human	Breast	Precancer	1.91e-03	1.36e-01	-0.0263
23168	RTF1	NCCBC14	Human	Breast	DCIS	2.58e-12	-1.35e-01	0.2021
23168	RTF1	NCCBC5	Human	Breast	DCIS	2.59e-11	-1.82e-01	0.2046
23168	RTF1	P1	Human	Breast	IDC	6.85e-19	-2.71e-01	0.1527

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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:00017017	Breast	Precancer	in utero embryonic development	35/1080	367/18723	2.47e-03	2.27e-02	35
GO:000170113	Breast	IDC	in utero embryonic development	42/1434	367/18723	5.85e-03	4.24e-02	42
GO:000170122	Breast	DCIS	in utero embryonic development	41/1390	367/18723	5.74e-03	4.13e-02	41
GO:00182057	Esophagus	HGIN	peptidyl-lysine modification	88/2587	376/18723	2.99e-07	1.39e-05	88
GO:00198277	Esophagus	HGIN	stem cell population maintenance	39/2587	131/18723	1.63e-06	6.14e-05	39
GO:00987278	Esophagus	HGIN	maintenance of cell number	39/2587	134/18723	3.02e-06	1.03e-04	39
GO:00063687	Esophagus	HGIN	transcription elongation from RNA polymerase II promoter	24/2587	69/18723	8.93e-06	2.64e-04	24
GO:00063548	Esophagus	HGIN	DNA-templated transcription, elongation	27/2587	91/18723	6.62e-05	1.52e-03	27
GO:000170118	Esophagus	HGIN	in utero embryonic development	77/2587	367/18723	9.56e-05	2.05e-03	77
GO:00165708	Esophagus	HGIN	histone modification	92/2587	463/18723	1.70e-04	3.30e-03	92
GO:00018244	Esophagus	HGIN	blastocyst development	28/2587	106/18723	4.30e-04	6.47e-03	28
GO:00310568	Esophagus	HGIN	regulation of histone modification	36/2587	152/18723	7.06e-04	9.52e-03	36
GO:00310604	Esophagus	HGIN	regulation of histone methylation	19/2587	69/18723	2.03e-03	2.13e-02	19
GO:001605516	Esophagus	HGIN	Wnt signaling pathway	83/2587	444/18723	2.27e-03	2.33e-02	83
GO:00515714	Esophagus	HGIN	positive regulation of histone H3-K4 methylation	8/2587	19/18723	2.40e-03	2.41e-02	8
GO:019873816	Esophagus	HGIN	cell-cell signaling by wnt	83/2587	446/18723	2.58e-03	2.55e-02	83
GO:00310624	Esophagus	HGIN	positive regulation of histone methylation	13/2587	41/18723	2.62e-03	2.58e-02	13
GO:00349688	Esophagus	HGIN	histone lysine methylation	27/2587	115/18723	3.51e-03	3.24e-02	27
GO:00064798	Esophagus	HGIN	protein methylation	38/2587	181/18723	5.05e-03	4.22e-02	38
GO:00082138	Esophagus	HGIN	protein alkylation	38/2587	181/18723	5.05e-03	4.22e-02	38

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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

RTF1

SNV

Missense_Mutation

rs764850999

c.518C>T

p.Ser173Leu

p.S173L

Q92541

protein_coding

tolerated(0.15)

possibly_damaging(0.879)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RTF1

SNV

Missense_Mutation

c.611G>C

p.Arg204Thr

p.R204T

Q92541

protein_coding

deleterious(0)

probably_damaging(0.915)

TCGA-AN-A0FS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

RTF1

SNV

Missense_Mutation

novel

c.662N>T

p.Arg221Ile

p.R221I

Q92541

protein_coding

deleterious(0)

probably_damaging(0.991)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

RTF1

SNV

Missense_Mutation

c.601G>A

p.Glu201Lys

p.E201K

Q92541

protein_coding

deleterious(0)

probably_damaging(0.978)

TCGA-C8-A8HQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

RTF1

insertion

Nonsense_Mutation

novel

c.2076_2077insACACGATTTTGATGTGAAGATTGACTTACAAGTTCCCA

p.Ala693ThrfsTer4

p.A693Tfs*4

Q92541

protein_coding

TCGA-A8-A07U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

RTF1

insertion

Nonsense_Mutation

novel

c.1614_1615insGGGCTGCAACTACGGTAGGAGGCACTTCTGGGGTAGCTT

p.Gln538_Leu539insGlyLeuGlnLeuArgTerGluAlaLeuLeuGlyTerLeu

p.Q538_L539insGLQLR*EALLG*L

Q92541

protein_coding

TCGA-A8-A0A4-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

RTF1

insertion

Frame_Shift_Ins

novel

c.597_598insTTAGCCACAAAACGGAATGAAATAATGGCCTTTGCAGCAACTTC

p.Thr200LeufsTer28

p.T200Lfs*28

Q92541

protein_coding

TCGA-AN-A04A-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

RTF1

SNV

Missense_Mutation

novel

c.1126N>T

p.Pro376Ser

p.P376S

Q92541

protein_coding

deleterious(0)

probably_damaging(0.987)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RTF1

SNV

Missense_Mutation

novel

c.1643N>T

p.Ala548Val

p.A548V

Q92541

protein_coding

tolerated(0.09)

probably_damaging(0.935)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RTF1

SNV

Missense_Mutation

c.1269C>G

p.Asn423Lys

p.N423K

Q92541

protein_coding

deleterious(0)

probably_damaging(0.982)

TCGA-Q1-A73O-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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