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: RPL3

Gene summary for RPL3

Gene summary.

Gene information	Species	Human
	Gene symbol	RPL3
	Gene ID	6122
	Gene name	ribosomal protein L3
	Gene Alias	ASC-1
	Cytomap	22q13.1
	Gene Type	protein-coding
	GO ID	GO:0000027
	UniProtAcc	P39023

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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
6122	RPL3	GSM4909280	Human	Breast	Precancer	2.18e-12	-6.46e-01	0.0305
6122	RPL3	GSM4909281	Human	Breast	IDC	2.23e-35	-2.37e-01	0.21
6122	RPL3	GSM4909282	Human	Breast	IDC	9.12e-25	-1.76e-01	-0.0288
6122	RPL3	GSM4909285	Human	Breast	IDC	9.51e-18	-1.41e-01	0.21
6122	RPL3	GSM4909286	Human	Breast	IDC	1.06e-04	9.58e-02	0.1081
6122	RPL3	GSM4909287	Human	Breast	IDC	4.22e-51	-4.28e-01	0.2057
6122	RPL3	GSM4909290	Human	Breast	IDC	3.72e-33	-3.03e-01	0.2096
6122	RPL3	GSM4909291	Human	Breast	IDC	5.44e-21	-2.69e-01	0.1753
6122	RPL3	GSM4909293	Human	Breast	IDC	3.26e-75	-3.22e-01	0.1581
6122	RPL3	GSM4909294	Human	Breast	IDC	6.91e-11	-1.37e-01	0.2022
6122	RPL3	GSM4909295	Human	Breast	IDC	6.82e-06	-2.05e-01	0.0898
6122	RPL3	GSM4909297	Human	Breast	IDC	3.32e-03	-8.60e-02	0.1517
6122	RPL3	GSM4909298	Human	Breast	IDC	1.84e-64	-2.99e-01	0.1551
6122	RPL3	GSM4909301	Human	Breast	IDC	1.41e-143	-7.65e-01	0.1577
6122	RPL3	GSM4909302	Human	Breast	IDC	4.26e-10	-1.96e-01	0.1545
6122	RPL3	GSM4909304	Human	Breast	IDC	2.09e-38	-2.05e-01	0.1636
6122	RPL3	GSM4909305	Human	Breast	IDC	5.52e-06	1.04e-01	0.0436
6122	RPL3	GSM4909307	Human	Breast	IDC	9.59e-04	-7.75e-02	0.1569
6122	RPL3	GSM4909312	Human	Breast	IDC	6.43e-20	1.44e-01	0.1552
6122	RPL3	GSM4909315	Human	Breast	IDC	2.04e-88	-5.25e-01	0.21

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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
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:00021819	Breast	Precancer	cytoplasmic translation	80/1080	148/18723	1.59e-59	8.54e-56	80
GO:00226139	Breast	Precancer	ribonucleoprotein complex biogenesis	79/1080	463/18723	2.11e-18	1.03e-15	79
GO:00718269	Breast	Precancer	ribonucleoprotein complex subunit organization	48/1080	227/18723	2.68e-15	8.45e-13	48
GO:00226189	Breast	Precancer	ribonucleoprotein complex assembly	47/1080	220/18723	3.47e-15	1.03e-12	47
GO:00422549	Breast	Precancer	ribosome biogenesis	52/1080	299/18723	7.35e-13	1.51e-10	52
GO:00064179	Breast	Precancer	regulation of translation	67/1080	468/18723	4.71e-12	7.64e-10	67
GO:00422559	Breast	Precancer	ribosome assembly	21/1080	61/18723	1.06e-11	1.53e-09	21
GO:00422739	Breast	Precancer	ribosomal large subunit biogenesis	22/1080	72/18723	5.03e-11	5.61e-09	22
GO:00422749	Breast	Precancer	ribosomal small subunit biogenesis	21/1080	73/18723	4.84e-10	4.39e-08	21
GO:19033209	Breast	Precancer	regulation of protein modification by small protein conjugation or removal	38/1080	242/18723	1.71e-08	1.17e-06	38
GO:00000289	Breast	Precancer	ribosomal small subunit assembly	10/1080	19/18723	2.24e-08	1.50e-06	10
GO:00063646	Breast	Precancer	rRNA processing	35/1080	225/18723	7.90e-08	4.60e-06	35
GO:19033219	Breast	Precancer	negative regulation of protein modification by small protein conjugation or removal	21/1080	95/18723	8.09e-08	4.61e-06	21
GO:00160726	Breast	Precancer	rRNA metabolic process	36/1080	236/18723	8.59e-08	4.84e-06	36
GO:00313969	Breast	Precancer	regulation of protein ubiquitination	33/1080	210/18723	1.45e-07	7.82e-06	33
GO:00313979	Breast	Precancer	negative regulation of protein ubiquitination	19/1080	83/18723	1.85e-07	9.54e-06	19
GO:19017989	Breast	Precancer	positive regulation of signal transduction by p53 class mediator	10/1080	25/18723	5.77e-07	2.49e-05	10
GO:19017969	Breast	Precancer	regulation of signal transduction by p53 class mediator	19/1080	93/18723	1.20e-06	4.60e-05	19
GO:00723319	Breast	Precancer	signal transduction by p53 class mediator	26/1080	163/18723	2.23e-06	7.76e-05	26
GO:00000279	Breast	Precancer	ribosomal large subunit assembly	9/1080	27/18723	1.24e-05	3.19e-04	9

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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

RPL3

insertion

Nonsense_Mutation

novel

c.451_452insAATGCCTGCCTGAAAGTCGGTTGTGAG

p.Ser151delinsLysCysLeuProGluSerArgLeuTerGly

p.S151delinsKCLPESRL*G

P39023

protein_coding

TCGA-A8-A09C-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RPL3

insertion

Nonsense_Mutation

novel

c.481_482insACCAGTAACACTGAAATGCCTGCCTGAAAGTCGGTTGTGAG

p.Arg161HisfsTer3

p.R161Hfs*3

P39023

protein_coding

TCGA-A8-A0A1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

RPL3

insertion

Frame_Shift_Ins

novel

c.114_115insT

p.Lys39Ter

p.K39*

P39023

protein_coding

TCGA-AN-A041-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

RPL3

insertion

Frame_Shift_Ins

novel

c.415_416insCTTCTCCCTT

p.Asp139AlafsTer5

p.D139Afs*5

P39023

protein_coding

TCGA-AO-A0J4-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

RPL3

insertion

Nonsense_Mutation

novel

c.446_447insATTCAACTGGTGACTCACCAGTAACACTGAAATGCCTGC

p.Asp149delinsGluPheAsnTrpTerLeuThrSerAsnThrGluMetProAla

p.D149delinsEFNW*LTSNTEMPA

P39023

protein_coding

TCGA-B6-A0RE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

RPL3

deletion

Frame_Shift_Del

novel

c.481delC

p.Arg161ValfsTer20

p.R161Vfs*20

P39023

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

RPL3

SNV

Missense_Mutation

c.1183N>A

p.Asp395Asn

p.D395N

P39023

protein_coding

deleterious(0.03)

benign(0.041)

TCGA-FU-A3EO-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

RPL3

SNV

Missense_Mutation

c.1086N>C

p.Lys362Asn

p.K362N

P39023

protein_coding

tolerated(0.2)

benign(0.001)

TCGA-FU-A3YQ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

RPL3

SNV

Missense_Mutation

novel

c.90G>T

p.Lys30Asn

p.K30N

P39023

protein_coding

deleterious(0)

possibly_damaging(0.776)

TCGA-MY-A5BF-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

RPL3

SNV

Missense_Mutation

novel

c.1036A>G

p.Thr346Ala

p.T346A

P39023

protein_coding

deleterious(0.05)

possibly_damaging(0.803)

TCGA-AA-3715-01

Colorectum

colon adenocarcinoma

Male

>=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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