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: RBBP8

Gene summary for RBBP8

Gene summary.

Gene information	Species	Human
	Gene symbol	RBBP8
	Gene ID	5932
	Gene name	RB binding protein 8, endonuclease
	Gene Alias	COM1
	Cytomap	18q11.2
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	A0A024RC34

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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
5932	RBBP8	HCC1_Meng	Human	Liver	HCC	1.26e-47	-2.42e-02	0.0246
5932	RBBP8	HCC2_Meng	Human	Liver	HCC	3.03e-10	1.85e-02	0.0107
5932	RBBP8	cirrhotic2	Human	Liver	Cirrhotic	2.61e-02	1.23e-01	0.0201
5932	RBBP8	HCC2	Human	Liver	HCC	6.33e-10	3.61e+00	0.5341
5932	RBBP8	S014	Human	Liver	HCC	7.13e-06	3.92e-01	0.2254
5932	RBBP8	S016	Human	Liver	HCC	9.31e-07	3.32e-01	0.2243
5932	RBBP8	S028	Human	Liver	HCC	7.45e-13	7.71e-01	0.2503
5932	RBBP8	S029	Human	Liver	HCC	5.03e-11	6.69e-01	0.2581
5932	RBBP8	RNA-P17T-P17T-6	Human	Lung	IAC	1.56e-03	4.78e-01	0.3385
5932	RBBP8	RNA-P25T1-P25T1-1	Human	Lung	AIS	5.76e-16	6.30e-01	-0.2116
5932	RBBP8	RNA-P25T1-P25T1-2	Human	Lung	AIS	1.85e-06	6.44e-01	-0.1941
5932	RBBP8	RNA-P25T1-P25T1-4	Human	Lung	AIS	4.49e-07	4.22e-01	-0.2119
5932	RBBP8	RNA-P7T1-P7T1-1	Human	Lung	AIS	2.48e-03	3.77e-01	-0.0961
5932	RBBP8	RNA-P7T1-P7T1-2	Human	Lung	AIS	2.50e-03	4.08e-01	-0.0876
5932	RBBP8	C04	Human	Oral cavity	OSCC	6.40e-18	1.01e+00	0.2633
5932	RBBP8	C21	Human	Oral cavity	OSCC	7.94e-18	9.35e-01	0.2678
5932	RBBP8	C30	Human	Oral cavity	OSCC	4.29e-28	1.38e+00	0.3055
5932	RBBP8	C38	Human	Oral cavity	OSCC	6.56e-03	8.45e-01	0.172
5932	RBBP8	C43	Human	Oral cavity	OSCC	2.55e-22	4.97e-01	0.1704
5932	RBBP8	C46	Human	Oral cavity	OSCC	9.16e-10	4.86e-01	0.1673

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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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:004477216	Esophagus	ESCC	mitotic cell cycle phase transition	281/8552	424/18723	4.63e-18	4.45e-16	281
GO:000170119	Esophagus	ESCC	in utero embryonic development	243/8552	367/18723	1.00e-15	6.86e-14	243
GO:00903053	Esophagus	ESCC	nucleic acid phosphodiester bond hydrolysis	163/8552	261/18723	3.07e-08	5.73e-07	163
GO:000008214	Esophagus	ESCC	G1/S transition of mitotic cell cycle	134/8552	214/18723	4.04e-07	5.55e-06	134
GO:004484314	Esophagus	ESCC	cell cycle G1/S phase transition	148/8552	241/18723	5.68e-07	7.48e-06	148
GO:000182412	Esophagus	ESCC	blastocyst development	73/8552	106/18723	1.13e-06	1.40e-05	73
GO:00063024	Esophagus	ESCC	double-strand break repair	152/8552	251/18723	1.33e-06	1.62e-05	152
GO:00063101	Esophagus	ESCC	DNA recombination	168/8552	305/18723	5.58e-04	3.05e-03	168
GO:00007241	Esophagus	ESCC	double-strand break repair via homologous recombination	79/8552	138/18723	4.05e-03	1.62e-02	79
GO:00007251	Esophagus	ESCC	recombinational repair	80/8552	140/18723	4.10e-03	1.63e-02	80
GO:0044772	Liver	NAFLD	mitotic cell cycle phase transition	67/1882	424/18723	1.25e-04	2.39e-03	67
GO:0044843	Liver	NAFLD	cell cycle G1/S phase transition	43/1882	241/18723	1.40e-04	2.63e-03	43
GO:0000082	Liver	NAFLD	G1/S transition of mitotic cell cycle	39/1882	214/18723	1.78e-04	3.14e-03	39
GO:00323553	Liver	NAFLD	response to estradiol	25/1882	141/18723	3.51e-03	3.01e-02	25
GO:00017015	Liver	Cirrhotic	in utero embryonic development	134/4634	367/18723	2.78e-07	6.86e-06	134
GO:00447721	Liver	Cirrhotic	mitotic cell cycle phase transition	139/4634	424/18723	1.02e-04	1.06e-03	139
GO:00323551	Liver	Cirrhotic	response to estradiol	51/4634	141/18723	1.60e-03	1.04e-02	51
GO:00000821	Liver	Cirrhotic	G1/S transition of mitotic cell cycle	72/4634	214/18723	2.07e-03	1.28e-02	72
GO:00448431	Liver	Cirrhotic	cell cycle G1/S phase transition	77/4634	241/18723	6.68e-03	3.30e-02	77
GO:00447722	Liver	HCC	mitotic cell cycle phase transition	240/7958	424/18723	2.47e-09	6.84e-08	240

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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

RBBP8

SNV

Missense_Mutation

c.2429N>T

p.Gly810Val

p.G810V

Q99708

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

RBBP8

SNV

Missense_Mutation

novel

c.2530N>A

p.Pro844Thr

p.P844T

Q99708

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

RBBP8

SNV

Missense_Mutation

c.2429N>T

p.Gly810Val

p.G810V

Q99708

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-D8-A1XL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide+tamoxifen

RBBP8

SNV

Missense_Mutation

rs201845876

c.1351N>A

p.Glu451Lys

p.E451K

Q99708

protein_coding

deleterious(0.01)

possibly_damaging(0.647)

TCGA-EW-A1J5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

RBBP8

SNV

Missense_Mutation

rs768802597

c.2254N>C

p.Glu752Gln

p.E752Q

Q99708

protein_coding

deleterious(0.02)

benign(0.116)

TCGA-EW-A1PB-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

RBBP8

insertion

Nonsense_Mutation

novel

c.2531_2532insTGATTACTGTTAGTAATTAATACTGTCTGTAAGA

p.Pro845AspfsTer4

p.P845Dfs*4

Q99708

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

RBBP8

insertion

Nonsense_Mutation

novel

c.1820_1821insTAAAATCTAGACAGAAGCA

p.Ser608LysfsTer3

p.S608Kfs*3

Q99708

protein_coding

TCGA-C8-A134-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

RBBP8

deletion

Frame_Shift_Del

c.1544_1571delNNNNNNNNNNNNNNNNNNNNNNNNNNNN

p.Lys515IlefsTer2

p.K515Ifs*2

Q99708

protein_coding

TCGA-D8-A146-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

RBBP8

SNV

Missense_Mutation

novel

c.2561N>C

p.Val854Ala

p.V854A

Q99708

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-C5-A8XI-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

RBBP8

SNV

Missense_Mutation

c.1951N>C

p.Glu651Gln

p.E651Q

Q99708

protein_coding

deleterious(0.01)

possibly_damaging(0.621)

TCGA-EA-A5ZF-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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