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: RPL23

Gene summary for RPL23

Gene summary.

Gene information	Species	Human
	Gene symbol	RPL23
	Gene ID	9349
	Gene name	ribosomal protein L23
	Gene Alias	L23
	Cytomap	17q12
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	A0A024R1Q8

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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
9349	RPL23	GSM4909281	Human	Breast	IDC	1.80e-20	-2.70e-01	0.21
9349	RPL23	GSM4909282	Human	Breast	IDC	5.55e-29	-3.92e-01	-0.0288
9349	RPL23	GSM4909286	Human	Breast	IDC	1.73e-54	3.58e-01	0.1081
9349	RPL23	GSM4909287	Human	Breast	IDC	4.03e-30	-5.41e-01	0.2057
9349	RPL23	GSM4909288	Human	Breast	IDC	1.16e-08	-3.95e-01	0.0988
9349	RPL23	GSM4909290	Human	Breast	IDC	1.04e-165	7.82e-01	0.2096
9349	RPL23	GSM4909292	Human	Breast	IDC	2.39e-47	7.31e-01	0.1236
9349	RPL23	GSM4909293	Human	Breast	IDC	9.17e-169	8.63e-01	0.1581
9349	RPL23	GSM4909294	Human	Breast	IDC	3.36e-41	3.46e-01	0.2022
9349	RPL23	GSM4909296	Human	Breast	IDC	7.60e-12	-2.97e-01	0.1524
9349	RPL23	GSM4909297	Human	Breast	IDC	1.43e-22	1.88e-02	0.1517
9349	RPL23	GSM4909299	Human	Breast	IDC	5.08e-03	1.77e-01	0.035
9349	RPL23	GSM4909302	Human	Breast	IDC	1.09e-09	5.24e-02	0.1545
9349	RPL23	GSM4909304	Human	Breast	IDC	6.67e-24	-2.95e-01	0.1636
9349	RPL23	GSM4909307	Human	Breast	IDC	2.47e-04	1.61e-01	0.1569
9349	RPL23	GSM4909308	Human	Breast	IDC	2.68e-12	2.26e-01	0.158
9349	RPL23	GSM4909309	Human	Breast	IDC	1.18e-07	-6.88e-02	0.0483
9349	RPL23	GSM4909311	Human	Breast	IDC	1.90e-37	-2.36e-01	0.1534
9349	RPL23	GSM4909316	Human	Breast	IDC	3.90e-10	-5.01e-01	0.21
9349	RPL23	GSM4909317	Human	Breast	IDC	5.22e-05	-1.74e-01	0.1355

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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
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
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
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:1903362110	Oral cavity	LP	regulation of cellular protein catabolic process	119/4623	255/18723	1.52e-14	1.76e-12	119
GO:0031647110	Oral cavity	LP	regulation of protein stability	132/4623	298/18723	8.16e-14	7.99e-12	132
GO:1903320110	Oral cavity	LP	regulation of protein modification by small protein conjugation or removal	111/4623	242/18723	4.81e-13	4.30e-11	111
GO:000691318	Oral cavity	LP	nucleocytoplasmic transport	130/4623	301/18723	1.19e-12	9.77e-11	130
GO:005116918	Oral cavity	LP	nuclear transport	130/4623	301/18723	1.19e-12	9.77e-11	130
GO:1903050110	Oral cavity	LP	regulation of proteolysis involved in cellular protein catabolic process	101/4623	221/18723	7.00e-12	5.48e-10	101
GO:0022411110	Oral cavity	LP	cellular component disassembly	173/4623	443/18723	9.97e-12	7.44e-10	173
GO:001703816	Oral cavity	LP	protein import	95/4623	206/18723	1.55e-11	1.13e-09	95
GO:0031396110	Oral cavity	LP	regulation of protein ubiquitination	95/4623	210/18723	5.88e-11	3.61e-09	95
GO:0050821110	Oral cavity	LP	protein stabilization	88/4623	191/18723	9.15e-11	5.51e-09	88
GO:2000058110	Oral cavity	LP	regulation of ubiquitin-dependent protein catabolic process	77/4623	164/18723	4.50e-10	2.22e-08	77
GO:0009895110	Oral cavity	LP	negative regulation of catabolic process	128/4623	320/18723	8.36e-10	3.91e-08	128
GO:003254313	Oral cavity	LP	mitochondrial translation	43/4623	76/18723	2.85e-09	1.26e-07	43
GO:0031330110	Oral cavity	LP	negative regulation of cellular catabolic process	107/4623	262/18723	5.25e-09	2.16e-07	107
GO:014005312	Oral cavity	LP	mitochondrial gene expression	53/4623	108/18723	3.54e-08	1.27e-06	53
GO:0072331110	Oral cavity	LP	signal transduction by p53 class mediator	72/4623	163/18723	3.99e-08	1.41e-06	72
GO:0051348110	Oral cavity	LP	negative regulation of transferase activity	106/4623	268/18723	4.60e-08	1.61e-06	106
GO:0031397110	Oral cavity	LP	negative regulation of protein ubiquitination	42/4623	83/18723	3.10e-07	9.17e-06	42
GO:0000027110	Oral cavity	LP	ribosomal large subunit assembly	19/4623	27/18723	7.41e-07	1.96e-05	19
GO:0042177110	Oral cavity	LP	negative regulation of protein catabolic process	54/4623	121/18723	1.28e-06	3.13e-05	54

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0301018	Breast	Precancer	Ribosome	80/684	167/8465	7.33e-44	2.32e-41	1.77e-41	80
hsa0517118	Breast	Precancer	Coronavirus disease - COVID-19	81/684	232/8465	3.74e-32	2.36e-30	1.81e-30	81
hsa0301019	Breast	Precancer	Ribosome	80/684	167/8465	7.33e-44	2.32e-41	1.77e-41	80
hsa0517119	Breast	Precancer	Coronavirus disease - COVID-19	81/684	232/8465	3.74e-32	2.36e-30	1.81e-30	81
hsa0301024	Breast	IDC	Ribosome	83/867	167/8465	6.07e-39	9.87e-37	7.38e-37	83
hsa0517124	Breast	IDC	Coronavirus disease - COVID-19	86/867	232/8465	1.50e-28	9.72e-27	7.27e-27	86
hsa0301034	Breast	IDC	Ribosome	83/867	167/8465	6.07e-39	9.87e-37	7.38e-37	83
hsa0517134	Breast	IDC	Coronavirus disease - COVID-19	86/867	232/8465	1.50e-28	9.72e-27	7.27e-27	86
hsa0301044	Breast	DCIS	Ribosome	82/846	167/8465	8.69e-39	1.40e-36	1.03e-36	82
hsa0517144	Breast	DCIS	Coronavirus disease - COVID-19	86/846	232/8465	2.42e-29	1.56e-27	1.15e-27	86
hsa0301054	Breast	DCIS	Ribosome	82/846	167/8465	8.69e-39	1.40e-36	1.03e-36	82
hsa0517154	Breast	DCIS	Coronavirus disease - COVID-19	86/846	232/8465	2.42e-29	1.56e-27	1.15e-27	86
hsa0517120	Cervix	CC	Coronavirus disease - COVID-19	111/1267	232/8465	1.82e-33	5.90e-31	3.49e-31	111
hsa0301020	Cervix	CC	Ribosome	85/1267	167/8465	3.17e-28	5.14e-26	3.04e-26	85
hsa05171110	Cervix	CC	Coronavirus disease - COVID-19	111/1267	232/8465	1.82e-33	5.90e-31	3.49e-31	111
hsa03010110	Cervix	CC	Ribosome	85/1267	167/8465	3.17e-28	5.14e-26	3.04e-26	85
hsa0301025	Cervix	HSIL_HPV	Ribosome	80/459	167/8465	9.61e-58	2.82e-55	2.28e-55	80
hsa0517125	Cervix	HSIL_HPV	Coronavirus disease - COVID-19	91/459	232/8465	2.14e-56	3.13e-54	2.53e-54	91
hsa0301035	Cervix	HSIL_HPV	Ribosome	80/459	167/8465	9.61e-58	2.82e-55	2.28e-55	80
hsa0517135	Cervix	HSIL_HPV	Coronavirus disease - COVID-19	91/459	232/8465	2.14e-56	3.13e-54	2.53e-54	91

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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

RPL23

SNV

Missense_Mutation

c.295N>C

p.Glu99Gln

p.E99Q

P62829

protein_coding

deleterious(0.01)

possibly_damaging(0.794)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RPL23

SNV

Missense_Mutation

novel

c.119T>G

p.Ile40Ser

p.I40S

P62829

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A0HK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

RPL23

SNV

Missense_Mutation

c.11N>A

p.Arg4Gln

p.R4Q

P62829

protein_coding

tolerated(0.19)

benign(0.328)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RPL23

insertion

Nonsense_Mutation

novel

c.149_150insGTTCCTGGCCATCCCTTGATTTACAAATGTGATGTTGATTTGT

p.Asn50LysfsTer7

p.N50Kfs*7

P62829

protein_coding

TCGA-A7-A0D9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

RPL23

insertion

Frame_Shift_Ins

novel

c.116_117insGAAAGGTAGGAAATCAGTC

p.Ile39MetfsTer27

p.I39Mfs*27

P62829

protein_coding

TCGA-BH-A0HK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

RPL23

SNV

Missense_Mutation

novel

c.254N>A

p.Arg85Gln

p.R85Q

P62829

protein_coding

tolerated(0.07)

benign(0.046)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RPL23

SNV

Missense_Mutation

novel

c.397G>A

p.Ala133Thr

p.A133T

P62829

protein_coding

deleterious(0.01)

benign(0.367)

TCGA-F4-6856-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Ancillary

leucovorin

RPL23

SNV

Missense_Mutation

novel

c.107N>G

p.Asn36Ser

p.N36S

P62829

protein_coding

tolerated(0.24)

benign(0.262)

TCGA-A5-A2K5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

RPL23

SNV

Missense_Mutation

c.213N>T

p.Glu71Asp

p.E71D

P62829

protein_coding

tolerated(0.32)

benign(0.248)

TCGA-B5-A11E-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

RPL23

SNV

Missense_Mutation

c.172G>T

p.Gly58Cys

p.G58C

P62829

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-D1-A17R-01

Endometrium

uterine corpus endometrioid carcinoma

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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