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: RPP40

Gene summary for RPP40

Gene summary.

Gene information	Species	Human
	Gene symbol	RPP40
	Gene ID	10799
	Gene name	ribonuclease P/MRP subunit p40
	Gene Alias	RNASEP1
	Cytomap	6p25.1
	Gene Type	protein-coding
	GO ID	GO:0000447
	UniProtAcc	O75818

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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
10799	RPP40	LZE4T	Human	Esophagus	ESCC	5.79e-05	2.21e-01	0.0811
10799	RPP40	LZE24T	Human	Esophagus	ESCC	3.76e-05	1.00e-01	0.0596
10799	RPP40	P2T-E	Human	Esophagus	ESCC	6.75e-11	1.99e-01	0.1177
10799	RPP40	P4T-E	Human	Esophagus	ESCC	5.31e-09	3.14e-01	0.1323
10799	RPP40	P5T-E	Human	Esophagus	ESCC	1.06e-04	1.54e-01	0.1327
10799	RPP40	P8T-E	Human	Esophagus	ESCC	1.96e-07	3.35e-02	0.0889
10799	RPP40	P9T-E	Human	Esophagus	ESCC	2.03e-19	2.10e-01	0.1131
10799	RPP40	P10T-E	Human	Esophagus	ESCC	1.02e-06	8.74e-02	0.116
10799	RPP40	P11T-E	Human	Esophagus	ESCC	4.49e-09	4.65e-01	0.1426
10799	RPP40	P12T-E	Human	Esophagus	ESCC	8.21e-15	2.26e-01	0.1122
10799	RPP40	P15T-E	Human	Esophagus	ESCC	6.61e-10	1.42e-01	0.1149
10799	RPP40	P16T-E	Human	Esophagus	ESCC	4.62e-11	1.90e-01	0.1153
10799	RPP40	P20T-E	Human	Esophagus	ESCC	8.66e-11	2.58e-01	0.1124
10799	RPP40	P21T-E	Human	Esophagus	ESCC	9.93e-16	4.44e-01	0.1617
10799	RPP40	P22T-E	Human	Esophagus	ESCC	6.12e-12	1.96e-01	0.1236
10799	RPP40	P23T-E	Human	Esophagus	ESCC	6.25e-15	3.63e-01	0.108
10799	RPP40	P24T-E	Human	Esophagus	ESCC	9.67e-11	1.83e-01	0.1287
10799	RPP40	P26T-E	Human	Esophagus	ESCC	1.79e-13	2.06e-01	0.1276
10799	RPP40	P27T-E	Human	Esophagus	ESCC	7.59e-10	2.01e-01	0.1055
10799	RPP40	P28T-E	Human	Esophagus	ESCC	6.89e-20	3.45e-01	0.1149

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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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ

∗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:0022613111	Esophagus	ESCC	ribonucleoprotein complex biogenesis	365/8552	463/18723	1.74e-49	1.11e-45	365
GO:0042254111	Esophagus	ESCC	ribosome biogenesis	252/8552	299/18723	3.27e-44	1.04e-40	252
GO:003447015	Esophagus	ESCC	ncRNA processing	300/8552	395/18723	3.09e-35	3.26e-32	300
GO:0016072110	Esophagus	ESCC	rRNA metabolic process	197/8552	236/18723	1.31e-33	1.18e-30	197
GO:0006364110	Esophagus	ESCC	rRNA processing	189/8552	225/18723	4.88e-33	3.87e-30	189
GO:003466012	Esophagus	ESCC	ncRNA metabolic process	346/8552	485/18723	4.35e-31	2.51e-28	346
GO:0042274111	Esophagus	ESCC	ribosomal small subunit biogenesis	67/8552	73/18723	6.62e-17	5.38e-15	67
GO:00905013	Esophagus	ESCC	RNA phosphodiester bond hydrolysis	110/8552	152/18723	1.95e-11	6.81e-10	110
GO:00304904	Esophagus	ESCC	maturation of SSU-rRNA	45/8552	50/18723	5.07e-11	1.63e-09	45
GO:00080333	Esophagus	ESCC	tRNA processing	92/8552	127/18723	7.83e-10	1.93e-08	92
GO:00063992	Esophagus	ESCC	tRNA metabolic process	122/8552	179/18723	9.03e-10	2.19e-08	122
GO:00903053	Esophagus	ESCC	nucleic acid phosphodiester bond hydrolysis	163/8552	261/18723	3.07e-08	5.73e-07	163
GO:00004623	Esophagus	ESCC	maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	32/8552	37/18723	2.96e-07	4.23e-06	32
GO:00004603	Esophagus	ESCC	maturation of 5.8S rRNA	30/8552	35/18723	1.07e-06	1.34e-05	30
GO:00004693	Esophagus	ESCC	cleavage involved in rRNA processing	24/8552	27/18723	3.48e-06	3.84e-05	24
GO:00004663	Esophagus	ESCC	maturation of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	21/8552	24/18723	2.57e-05	2.17e-04	21
GO:00905023	Esophagus	ESCC	RNA phosphodiester bond hydrolysis, endonucleolytic	55/8552	82/18723	7.34e-05	5.51e-04	55
GO:00004783	Esophagus	ESCC	endonucleolytic cleavage involved in rRNA processing	14/8552	15/18723	1.47e-04	9.85e-04	14
GO:00004793	Esophagus	ESCC	endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	14/8552	15/18723	1.47e-04	9.85e-04	14
GO:00344713	Esophagus	ESCC	ncRNA 5'-end processing	18/8552	21/18723	1.81e-04	1.16e-03	18

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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

RPP40

SNV

Missense_Mutation

rs761282652

c.638N>T

p.Thr213Met

p.T213M

O75818

protein_coding

deleterious(0.04)

possibly_damaging(0.751)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

RPP40

SNV

Missense_Mutation

c.908N>G

p.Glu303Gly

p.E303G

O75818

protein_coding

deleterious(0)

possibly_damaging(0.622)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

RPP40

SNV

Missense_Mutation

c.1008N>C

p.Glu336Asp

p.E336D

O75818

protein_coding

deleterious(0.03)

possibly_damaging(0.789)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

RPP40

SNV

Missense_Mutation

rs752857918

c.676N>A

p.Glu226Lys

p.E226K

O75818

protein_coding

tolerated(0.35)

benign(0.012)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

RPP40

SNV

Missense_Mutation

novel

c.494N>C

p.Ile165Thr

p.I165T

O75818

protein_coding

tolerated(0.12)

benign(0.003)

TCGA-AX-A2HD-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

RPP40

SNV

Missense_Mutation

novel

c.526N>C

p.Lys176Gln

p.K176Q

O75818

protein_coding

tolerated(0.24)

benign(0.371)

TCGA-B5-A1MR-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

RPP40

SNV

Missense_Mutation

rs138760401

c.961C>T

p.Pro321Ser

p.P321S

O75818

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BG-A222-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

RPP40

SNV

Missense_Mutation

c.1031N>G

p.Phe344Cys

p.F344C

O75818

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BS-A0UF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

RPP40

SNV

Missense_Mutation

c.456N>C

p.Glu152Asp

p.E152D

O75818

protein_coding

tolerated(1)

benign(0)

TCGA-BS-A0UF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

RPP40

SNV

Missense_Mutation

c.220N>T

p.Leu74Phe

p.L74F

O75818

protein_coding

deleterious(0.01)

probably_damaging(0.926)

TCGA-D1-A103-01

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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