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: RC3H2

Gene summary for RC3H2

Gene summary.

Gene information	Species	Human
	Gene symbol	RC3H2
	Gene ID	54542
	Gene name	ring finger and CCCH-type domains 2
	Gene Alias	MNAB
	Cytomap	9q33.2
	Gene Type	protein-coding
	GO ID	GO:0000209
	UniProtAcc	A0A024R899

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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
54542	RC3H2	CCI_1	Human	Cervix	CC	5.64e-04	5.02e-01	0.528
54542	RC3H2	CCI_2	Human	Cervix	CC	1.93e-10	1.16e+00	0.5249
54542	RC3H2	CCI_3	Human	Cervix	CC	6.11e-09	7.17e-01	0.516
54542	RC3H2	LZE4T	Human	Esophagus	ESCC	1.74e-09	3.12e-01	0.0811
54542	RC3H2	LZE5T	Human	Esophagus	ESCC	8.16e-05	4.14e-01	0.0514
54542	RC3H2	LZE7T	Human	Esophagus	ESCC	2.07e-05	4.73e-01	0.0667
54542	RC3H2	LZE20T	Human	Esophagus	ESCC	8.89e-04	2.55e-01	0.0662
54542	RC3H2	LZE24T	Human	Esophagus	ESCC	4.15e-18	3.79e-01	0.0596
54542	RC3H2	LZE21T	Human	Esophagus	ESCC	1.63e-04	2.23e-01	0.0655
54542	RC3H2	P1T-E	Human	Esophagus	ESCC	3.58e-05	3.38e-01	0.0875
54542	RC3H2	P2T-E	Human	Esophagus	ESCC	5.18e-25	4.76e-01	0.1177
54542	RC3H2	P4T-E	Human	Esophagus	ESCC	5.59e-18	3.55e-01	0.1323
54542	RC3H2	P5T-E	Human	Esophagus	ESCC	1.72e-08	1.14e-01	0.1327
54542	RC3H2	P8T-E	Human	Esophagus	ESCC	2.04e-16	2.48e-01	0.0889
54542	RC3H2	P9T-E	Human	Esophagus	ESCC	1.53e-12	2.67e-01	0.1131
54542	RC3H2	P10T-E	Human	Esophagus	ESCC	1.62e-21	4.13e-01	0.116
54542	RC3H2	P11T-E	Human	Esophagus	ESCC	4.99e-03	3.51e-01	0.1426
54542	RC3H2	P12T-E	Human	Esophagus	ESCC	1.30e-17	2.83e-01	0.1122
54542	RC3H2	P15T-E	Human	Esophagus	ESCC	4.59e-10	2.99e-01	0.1149
54542	RC3H2	P16T-E	Human	Esophagus	ESCC	1.17e-13	1.76e-01	0.1153

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
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:00026984	Oral cavity	EOLP	negative regulation of immune effector process	26/2218	110/18723	3.94e-04	3.53e-03	26
GO:00508681	Oral cavity	EOLP	negative regulation of T cell activation	28/2218	122/18723	4.03e-04	3.58e-03	28
GO:0042093	Oral cavity	EOLP	T-helper cell differentiation	18/2218	66/18723	4.94e-04	4.31e-03	18
GO:00026974	Oral cavity	EOLP	regulation of immune effector process	61/2218	339/18723	5.48e-04	4.68e-03	61
GO:00022864	Oral cavity	EOLP	T cell activation involved in immune response	26/2218	114/18723	7.06e-04	5.78e-03	26
GO:0002294	Oral cavity	EOLP	CD4-positive, alpha-beta T cell differentiation involved in immune response	18/2218	68/18723	7.29e-04	5.94e-03	18
GO:0002287	Oral cavity	EOLP	alpha-beta T cell activation involved in immune response	18/2218	69/18723	8.79e-04	6.75e-03	18
GO:0002293	Oral cavity	EOLP	alpha-beta T cell differentiation involved in immune response	18/2218	69/18723	8.79e-04	6.75e-03	18
GO:0002292	Oral cavity	EOLP	T cell differentiation involved in immune response	19/2218	75/18723	9.43e-04	7.15e-03	19
GO:0046636	Oral cavity	EOLP	negative regulation of alpha-beta T cell activation	13/2218	43/18723	1.03e-03	7.63e-03	13
GO:00017761	Oral cavity	EOLP	leukocyte homeostasis	21/2218	87/18723	1.03e-03	7.63e-03	21
GO:00456203	Oral cavity	EOLP	negative regulation of lymphocyte differentiation	15/2218	55/18723	1.42e-03	9.62e-03	15
GO:0046639	Oral cavity	EOLP	negative regulation of alpha-beta T cell differentiation	9/2218	26/18723	2.14e-03	1.34e-02	9
GO:00455811	Oral cavity	EOLP	negative regulation of T cell differentiation	13/2218	47/18723	2.52e-03	1.53e-02	13
GO:0043371	Oral cavity	EOLP	negative regulation of CD4-positive, alpha-beta T cell differentiation	8/2218	22/18723	2.64e-03	1.59e-02	8
GO:2000515	Oral cavity	EOLP	negative regulation of CD4-positive, alpha-beta T cell activation	10/2218	32/18723	2.93e-03	1.72e-02	10
GO:00028223	Oral cavity	EOLP	regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	32/2218	168/18723	4.37e-03	2.38e-02	32
GO:190122221	Oral cavity	EOLP	regulation of NIK/NF-kappaB signaling	23/2218	112/18723	5.70e-03	2.92e-02	23
GO:00024604	Oral cavity	EOLP	adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	58/2218	356/18723	7.27e-03	3.52e-02	58
GO:00105866	Oral cavity	EOLP	miRNA metabolic process	8/2218	27/18723	1.07e-02	4.75e-02	8

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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

RC3H2

SNV

Missense_Mutation

novel

c.464N>A

p.Ala155Asp

p.A155D

Q9HBD1

protein_coding

deleterious(0)

possibly_damaging(0.72)

TCGA-AC-A8OS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RC3H2

SNV

Missense_Mutation

c.1393G>T

p.Val465Leu

p.V465L

Q9HBD1

protein_coding

tolerated(0.5)

possibly_damaging(0.785)

TCGA-B6-A0RU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

RC3H2

SNV

Missense_Mutation

c.2117A>G

p.Tyr706Cys

p.Y706C

Q9HBD1

protein_coding

deleterious(0.01)

probably_damaging(0.984)

TCGA-D8-A140-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin+cyclophosphamid

RC3H2

SNV

Missense_Mutation

novel

c.2009N>T

p.Ser670Phe

p.S670F

Q9HBD1

protein_coding

tolerated(0.1)

benign(0.445)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RC3H2

SNV

Missense_Mutation

c.1768C>G

p.Pro590Ala

p.P590A

Q9HBD1

protein_coding

deleterious(0.01)

probably_damaging(0.956)

TCGA-E2-A10C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

RC3H2

SNV

Missense_Mutation

c.2123N>A

p.Arg708Gln

p.R708Q

Q9HBD1

protein_coding

deleterious(0.02)

possibly_damaging(0.885)

TCGA-EW-A1OV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

epirubicin

RC3H2

insertion

Nonsense_Mutation

novel

c.2499_2500insCCCAAGTAGCTGGGATTATAGACATGCACCACC

p.Leu833_Ser834insProLysTerLeuGlyLeuTerThrCysThrThr

p.L833_S834insPK*LGL*TCTT

Q9HBD1

protein_coding

TCGA-A2-A0EX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

RC3H2

SNV

Missense_Mutation

rs370277433

c.2792N>T

p.Ala931Val

p.A931V

Q9HBD1

protein_coding

deleterious(0.05)

benign(0.018)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RC3H2

SNV

Missense_Mutation

c.2737N>T

p.Arg913Cys

p.R913C

Q9HBD1

protein_coding

deleterious(0)

probably_damaging(0.973)

TCGA-EA-A50E-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

RC3H2

SNV

Missense_Mutation

c.1259N>C

p.Arg420Pro

p.R420P

Q9HBD1

protein_coding

deleterious(0.01)

possibly_damaging(0.89)

TCGA-IR-A3LA-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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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