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: RPL18

Gene summary for RPL18

Gene summary.

Gene information	Species	Human
	Gene symbol	RPL18
	Gene ID	6141
	Gene name	ribosomal protein L18
	Gene Alias	DBA18
	Cytomap	19q13.33
	Gene Type	protein-coding
	GO ID	GO:0002181
	UniProtAcc	A0A024QZD1

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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
6141	RPL18	Dong_P1	Human	Prostate	Tumor	9.50e-05	5.85e-02	0.035
6141	RPL18	Dong_P3	Human	Prostate	Tumor	2.64e-02	7.11e-02	0.0278
6141	RPL18	Dong_P5	Human	Prostate	Tumor	8.31e-44	1.81e-01	0.053
6141	RPL18	Dong_P6	Human	Prostate	Tumor	2.17e-26	2.14e-01	0.0371
6141	RPL18	P7	Human	Prostate	Tumor	3.52e-45	2.24e+00	-0.1025
6141	RPL18	P9	Human	Prostate	Tumor	1.71e-07	7.43e-01	-0.0285
6141	RPL18	P10	Human	Prostate	Tumor	1.09e-16	1.70e+00	-0.0902
6141	RPL18	GSM5353217_PA_PB1A_Pool_2_S107_L004	Human	Prostate	Tumor	1.23e-03	-4.67e-01	0.156
6141	RPL18	GSM5353218_PA_PB1B_Pool_1_2_S74_L003	Human	Prostate	Tumor	1.82e-05	-3.36e-01	0.1479
6141	RPL18	GSM5353220_PA_PB1B_Pool_3_S51_L002	Human	Prostate	Tumor	8.59e-04	-3.45e-01	0.1531
6141	RPL18	GSM5353221_PA_PB2A_Pool_1_3_S25_L001	Human	Prostate	Tumor	9.94e-11	-1.94e-01	0.1633
6141	RPL18	GSM5353222_PA_PB2B_Pool_1_3_S52_L002	Human	Prostate	Tumor	5.07e-13	-3.05e-01	0.1608
6141	RPL18	GSM5353223_PA_PB2B_Pool_2_S26_L001	Human	Prostate	Tumor	4.09e-05	-2.17e-01	0.1604
6141	RPL18	GSM5353224_PA_PR5186_Pool_1_2_3_S27_L001	Human	Prostate	Tumor	1.22e-07	-1.64e-01	0.1621
6141	RPL18	GSM5353225_PA_PR5196-1_Pool_1_2_3_S53_L002	Human	Prostate	Tumor	2.33e-07	-2.58e-01	0.1619
6141	RPL18	GSM5353227_PA_PR5199-193K_Pool_1_2_3_S55_L002	Human	Prostate	Tumor	3.02e-17	-3.80e-01	0.1602
6141	RPL18	GSM5353228_PA_PR5199-640K_Pool_1_3_S108_L004	Human	Prostate	Tumor	1.11e-05	-6.60e-01	0.1537
6141	RPL18	GSM5353232_PA_PR5249_T1_S3_L001	Human	Prostate	Tumor	5.13e-07	-6.07e-01	0.1439
6141	RPL18	GSM5353236_PA_PR5251_T1_S7_L001	Human	Prostate	Tumor	3.92e-02	-2.48e-01	0.1608
6141	RPL18	GSM5353243_PA_PR5261_T1_S23_L002	Human	Prostate	Tumor	1.31e-13	-3.49e-01	0.1545

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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:00021819	Breast	Precancer	cytoplasmic translation	80/1080	148/18723	1.59e-59	8.54e-56	80
GO:000218114	Breast	IDC	cytoplasmic translation	82/1434	148/18723	2.60e-52	1.48e-48	82
GO:000218124	Breast	DCIS	cytoplasmic translation	82/1390	148/18723	2.21e-53	1.25e-49	82
GO:000218110	Cervix	CC	cytoplasmic translation	96/2311	148/18723	4.87e-51	2.91e-47	96
GO:000218115	Cervix	HSIL_HPV	cytoplasmic translation	86/737	148/18723	3.97e-82	1.91e-78	86
GO:0002181	Colorectum	AD	cytoplasmic translation	109/3918	148/18723	3.40e-43	2.13e-39	109
GO:0006839	Colorectum	AD	mitochondrial transport	102/3918	254/18723	1.87e-12	3.08e-10	102
GO:1990542	Colorectum	AD	mitochondrial transmembrane transport	47/3918	102/18723	1.09e-08	6.52e-07	47
GO:0006403	Colorectum	AD	RNA localization	71/3918	201/18723	1.54e-06	4.76e-05	71
GO:0051236	Colorectum	AD	establishment of RNA localization	58/3918	166/18723	1.95e-05	4.01e-04	58
GO:0015931	Colorectum	AD	nucleobase-containing compound transport	73/3918	222/18723	2.02e-05	4.10e-04	73
GO:0050657	Colorectum	AD	nucleic acid transport	57/3918	163/18723	2.22e-05	4.39e-04	57
GO:0050658	Colorectum	AD	RNA transport	57/3918	163/18723	2.22e-05	4.39e-04	57
GO:00021811	Colorectum	SER	cytoplasmic translation	102/2897	148/18723	1.38e-48	8.49e-45	102
GO:00068391	Colorectum	SER	mitochondrial transport	87/2897	254/18723	7.91e-14	3.03e-11	87
GO:19905421	Colorectum	SER	mitochondrial transmembrane transport	42/2897	102/18723	3.65e-10	4.77e-08	42
GO:00064031	Colorectum	SER	RNA localization	53/2897	201/18723	4.51e-05	1.13e-03	53
GO:00159311	Colorectum	SER	nucleobase-containing compound transport	54/2897	222/18723	3.65e-04	5.67e-03	54
GO:00512361	Colorectum	SER	establishment of RNA localization	42/2897	166/18723	6.70e-04	8.96e-03	42
GO:00506571	Colorectum	SER	nucleic acid transport	41/2897	163/18723	8.74e-04	1.06e-02	41

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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

RPL18

SNV

Missense_Mutation

novel

c.116N>A

p.Thr39Asn

p.T39N

Q07020

protein_coding

deleterious(0.02)

probably_damaging(0.929)

TCGA-3C-AAAU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

zoladex

RPL18

SNV

Missense_Mutation

rs368131281

c.437N>A

p.Arg146Gln

p.R146Q

Q07020

protein_coding

tolerated(0.05)

benign(0.377)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

RPL18

SNV

Missense_Mutation

novel

c.473C>T

p.Thr158Ile

p.T158I

Q07020

protein_coding

tolerated(0.11)

benign(0.017)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

RPL18

SNV

Missense_Mutation

novel

c.499G>T

p.Val167Phe

p.V167F

Q07020

protein_coding

deleterious(0.01)

benign(0.25)

TCGA-AX-A2H7-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

RPL18

SNV

Missense_Mutation

c.264N>A

p.Asp88Glu

p.D88E

Q07020

protein_coding

deleterious(0)

probably_damaging(0.933)

TCGA-B5-A11H-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Hormone Therapy

megace

RPL18

SNV

Missense_Mutation

novel

c.383N>C

p.Leu128Pro

p.L128P

Q07020

protein_coding

deleterious(0.01)

possibly_damaging(0.841)

TCGA-FI-A2D0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

RPL18

SNV

Missense_Mutation

novel

c.503N>A

p.Arg168His

p.R168H

Q07020

protein_coding

tolerated(0.1)

benign(0.097)

TCGA-FI-A2D5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatinum

RPL18

SNV

Missense_Mutation

c.79N>A

p.Leu27Met

p.L27M

Q07020

protein_coding

deleterious(0.02)

probably_damaging(0.955)

TCGA-G3-A7M9-01

Liver

liver hepatocellular carcinoma

Male

>=65

III/IV

Unknown

RPL18

insertion

In_Frame_Ins

novel

c.25_26insGGAGGTGGAGCTTGC

p.Lys9delinsArgArgTrpSerLeuGln

p.K9delinsRRWSLQ

Q07020

protein_coding

TCGA-ZS-A9CG-01

Liver

liver hepatocellular carcinoma

Male

<65

I/II

Unknown

RPL18

SNV

Missense_Mutation

c.263N>G

p.Asp88Gly

p.D88G

Q07020

protein_coding

deleterious(0)

probably_damaging(0.933)

TCGA-BR-8591-01

Stomach

stomach adenocarcinoma

Male

>=65

III/IV

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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