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	LZE4T	Human	Esophagus	ESCC	2.02e-06	5.21e-01	0.0811
5932	RBBP8	LZE7T	Human	Esophagus	ESCC	5.64e-07	8.30e-01	0.0667
5932	RBBP8	LZE8T	Human	Esophagus	ESCC	3.23e-10	3.99e-01	0.067
5932	RBBP8	LZE20T	Human	Esophagus	ESCC	1.06e-06	2.64e-02	0.0662
5932	RBBP8	LZE24T	Human	Esophagus	ESCC	6.48e-05	2.13e-01	0.0596
5932	RBBP8	LZE6T	Human	Esophagus	ESCC	2.55e-05	1.21e-01	0.0845
5932	RBBP8	P1T-E	Human	Esophagus	ESCC	5.00e-03	6.90e-01	0.0875
5932	RBBP8	P2T-E	Human	Esophagus	ESCC	2.62e-70	1.40e+00	0.1177
5932	RBBP8	P4T-E	Human	Esophagus	ESCC	5.73e-26	9.59e-01	0.1323
5932	RBBP8	P5T-E	Human	Esophagus	ESCC	4.13e-06	2.30e-01	0.1327
5932	RBBP8	P8T-E	Human	Esophagus	ESCC	9.89e-17	4.60e-01	0.0889
5932	RBBP8	P9T-E	Human	Esophagus	ESCC	4.71e-18	5.92e-01	0.1131
5932	RBBP8	P10T-E	Human	Esophagus	ESCC	3.71e-41	7.27e-01	0.116
5932	RBBP8	P11T-E	Human	Esophagus	ESCC	1.39e-09	1.06e+00	0.1426
5932	RBBP8	P12T-E	Human	Esophagus	ESCC	6.65e-39	7.80e-01	0.1122
5932	RBBP8	P15T-E	Human	Esophagus	ESCC	3.81e-29	7.91e-01	0.1149
5932	RBBP8	P16T-E	Human	Esophagus	ESCC	1.89e-30	6.71e-01	0.1153
5932	RBBP8	P17T-E	Human	Esophagus	ESCC	1.64e-16	8.49e-01	0.1278
5932	RBBP8	P20T-E	Human	Esophagus	ESCC	2.00e-28	7.57e-01	0.1124
5932	RBBP8	P21T-E	Human	Esophagus	ESCC	2.86e-59	1.34e+00	0.1617

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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:000008212	Prostate	Tumor	G1/S transition of mitotic cell cycle	62/3246	214/18723	1.63e-05	2.18e-04	62
GO:004484312	Prostate	Tumor	cell cycle G1/S phase transition	67/3246	241/18723	3.28e-05	3.88e-04	67
GO:004477214	Prostate	Tumor	mitotic cell cycle phase transition	106/3246	424/18723	3.61e-05	4.21e-04	106
GO:003235515	Prostate	Tumor	response to estradiol	38/3246	141/18723	2.78e-03	1.52e-02	38
GO:000170120	Skin	AK	in utero embryonic development	75/1910	367/18723	3.09e-09	2.62e-07	75
GO:004477210	Skin	AK	mitotic cell cycle phase transition	83/1910	424/18723	3.81e-09	3.05e-07	83
GO:00000828	Skin	AK	G1/S transition of mitotic cell cycle	50/1910	214/18723	1.57e-08	9.40e-07	50
GO:00448438	Skin	AK	cell cycle G1/S phase transition	52/1910	241/18723	1.32e-07	5.80e-06	52
GO:003235510	Skin	AK	response to estradiol	30/1910	141/18723	7.41e-05	1.06e-03	30
GO:00018245	Skin	AK	blastocyst development	24/1910	106/18723	1.38e-04	1.69e-03	24
GO:003235517	Skin	SCCIS	response to estradiol	17/919	141/18723	5.55e-04	8.47e-03	17
GO:004484315	Skin	SCCIS	cell cycle G1/S phase transition	24/919	241/18723	8.16e-04	1.10e-02	24
GO:000008215	Skin	SCCIS	G1/S transition of mitotic cell cycle	22/919	214/18723	8.70e-04	1.14e-02	22
GO:0001701110	Skin	SCCIS	in utero embryonic development	32/919	367/18723	1.23e-03	1.45e-02	32
GO:004477217	Skin	SCCIS	mitotic cell cycle phase transition	33/919	424/18723	6.22e-03	4.76e-02	33
GO:004477223	Skin	cSCC	mitotic cell cycle phase transition	180/4864	424/18723	7.09e-14	4.45e-12	180
GO:000170124	Skin	cSCC	in utero embryonic development	150/4864	367/18723	2.47e-10	1.04e-08	150
GO:000182413	Skin	cSCC	blastocyst development	53/4864	106/18723	9.74e-08	2.32e-06	53
GO:000008222	Skin	cSCC	G1/S transition of mitotic cell cycle	85/4864	214/18723	6.90e-06	9.60e-05	85
GO:004484322	Skin	cSCC	cell cycle G1/S phase transition	92/4864	241/18723	1.95e-05	2.28e-04	92

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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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