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: DICER1

Gene summary for DICER1

Gene summary.

Gene information	Species	Human
	Gene symbol	DICER1
	Gene ID	23405
	Gene name	dicer 1, ribonuclease III
	Gene Alias	DCR1
	Cytomap	14q32.13
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	Q9UPY3

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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
23405	DICER1	EOLP-1	Human	Oral cavity	EOLP	4.91e-07	1.91e-01	-0.0202
23405	DICER1	NEOLP-2	Human	Oral cavity	NEOLP	2.94e-05	1.73e-01	-0.0196
23405	DICER1	NEOLP-3	Human	Oral cavity	NEOLP	3.25e-05	2.39e-01	-0.0191
23405	DICER1	SYSMH1	Human	Oral cavity	OSCC	4.61e-18	3.77e-01	0.1127
23405	DICER1	SYSMH2	Human	Oral cavity	OSCC	5.86e-19	5.08e-01	0.2326
23405	DICER1	SYSMH3	Human	Oral cavity	OSCC	2.70e-25	7.59e-01	0.2442
23405	DICER1	SYSMH5	Human	Oral cavity	OSCC	1.01e-14	4.79e-01	0.0647
23405	DICER1	SYSMH6	Human	Oral cavity	OSCC	1.10e-03	1.59e-01	0.1275
23405	DICER1	HTA12-23-1	Human	Pancreas	PDAC	1.02e-04	7.42e-01	0.3405
23405	DICER1	HTA12-25-1	Human	Pancreas	PDAC	2.40e-03	4.78e-01	0.313
23405	DICER1	HTA12-26-1	Human	Pancreas	PDAC	3.87e-12	7.40e-01	0.3728
23405	DICER1	HTA12-29-1	Human	Pancreas	PDAC	1.66e-26	6.51e-01	0.3722
23405	DICER1	GSM5252130_BPH340PrGF_Via	Human	Prostate	BPH	4.98e-08	3.05e-01	-0.1972
23405	DICER1	GSM5252132_BPH389PrGF	Human	Prostate	BPH	1.49e-11	7.17e-01	-0.2247
23405	DICER1	GSM5252133_BPH389PrSF	Human	Prostate	BPH	2.44e-02	5.89e-01	-0.2027
23405	DICER1	GSM5252135_BPH511PrPUr_Fcol_3GEX	Human	Prostate	BPH	1.32e-08	5.04e-01	-0.1833
23405	DICER1	GSM5252137_BPH556PrGA2_Fcol	Human	Prostate	BPH	3.39e-08	6.49e-01	-0.23
23405	DICER1	047563_1562-all-cells	Human	Prostate	BPH	9.79e-04	1.37e-01	0.0791
23405	DICER1	048752_1579-all-cells	Human	Prostate	BPH	6.32e-13	4.35e-01	0.1008
23405	DICER1	052095_1628-all-cells	Human	Prostate	BPH	1.92e-10	4.07e-01	0.1032

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0022618	Colorectum	AD	ribonucleoprotein complex assembly	92/3918	220/18723	1.49e-12	2.60e-10	92
GO:0071826	Colorectum	AD	ribonucleoprotein complex subunit organization	94/3918	227/18723	1.70e-12	2.87e-10	94
GO:0022411	Colorectum	AD	cellular component disassembly	147/3918	443/18723	8.53e-10	6.76e-08	147
GO:0006401	Colorectum	AD	RNA catabolic process	102/3918	278/18723	8.64e-10	6.76e-08	102
GO:0022613	Colorectum	AD	ribonucleoprotein complex biogenesis	151/3918	463/18723	1.96e-09	1.39e-07	151
GO:0044270	Colorectum	AD	cellular nitrogen compound catabolic process	147/3918	451/18723	3.35e-09	2.23e-07	147
GO:0046700	Colorectum	AD	heterocycle catabolic process	145/3918	445/18723	4.37e-09	2.84e-07	145
GO:0034655	Colorectum	AD	nucleobase-containing compound catabolic process	133/3918	407/18723	1.56e-08	9.12e-07	133
GO:0019439	Colorectum	AD	aromatic compound catabolic process	146/3918	467/18723	7.48e-08	3.84e-06	146
GO:1901361	Colorectum	AD	organic cyclic compound catabolic process	153/3918	495/18723	8.23e-08	4.18e-06	153
GO:0010720	Colorectum	AD	positive regulation of cell development	87/3918	298/18723	4.17e-04	4.71e-03	87
GO:0050767	Colorectum	AD	regulation of neurogenesis	99/3918	364/18723	2.35e-03	1.82e-02	99
GO:0035196	Colorectum	AD	production of miRNAs involved in gene silencing by miRNA	20/3918	52/18723	2.87e-03	2.14e-02	20
GO:0031050	Colorectum	AD	dsRNA processing	20/3918	54/18723	4.76e-03	3.22e-02	20
GO:0070918	Colorectum	AD	production of small RNA involved in gene silencing by RNA	20/3918	54/18723	4.76e-03	3.22e-02	20
GO:00226181	Colorectum	SER	ribonucleoprotein complex assembly	69/2897	220/18723	2.25e-09	2.15e-07	69
GO:00718261	Colorectum	SER	ribonucleoprotein complex subunit organization	70/2897	227/18723	3.83e-09	3.51e-07	70
GO:00224111	Colorectum	SER	cellular component disassembly	114/2897	443/18723	1.17e-08	9.59e-07	114
GO:00226131	Colorectum	SER	ribonucleoprotein complex biogenesis	112/2897	463/18723	5.01e-07	2.48e-05	112
GO:00442701	Colorectum	SER	cellular nitrogen compound catabolic process	99/2897	451/18723	1.46e-04	2.86e-03	99

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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

DICER1

SNV

Missense_Mutation

novel

c.4430C>G

p.Ser1477Cys

p.S1477C

Q9UPY3

protein_coding

deleterious_low_confidence(0.02)

possibly_damaging(0.733)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

DICER1

SNV

Missense_Mutation

c.3037N>A

p.Pro1013Thr

p.P1013T

Q9UPY3

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

DICER1

SNV

Missense_Mutation

c.2326N>T

p.Val776Phe

p.V776F

Q9UPY3

protein_coding

deleterious(0.02)

probably_damaging(0.979)

TCGA-A8-A06Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DICER1

SNV

Missense_Mutation

c.5240N>T

p.Ser1747Leu

p.S1747L

Q9UPY3

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-A8-A092-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

DICER1

SNV

Missense_Mutation

novel

c.1490N>C

p.Glu497Ala

p.E497A

Q9UPY3

protein_coding

tolerated(0.06)

probably_damaging(0.995)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DICER1

SNV

Missense_Mutation

c.2084C>T

p.Ala695Val

p.A695V

Q9UPY3

protein_coding

deleterious(0)

probably_damaging(0.984)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DICER1

SNV

Missense_Mutation

novel

c.322N>G

p.Gln108Glu

p.Q108E

Q9UPY3

protein_coding

tolerated(0.59)

benign(0.055)

TCGA-BH-A2L8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

DICER1

SNV

Missense_Mutation

rs752424727

c.1778C>T

p.Ser593Leu

p.S593L

Q9UPY3

protein_coding

tolerated(0.2)

benign(0.033)

TCGA-D8-A1JG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

DICER1

SNV

Missense_Mutation

c.4529N>A

p.Cys1510Tyr

p.C1510Y

Q9UPY3

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-D8-A1JI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine

DICER1

SNV

Missense_Mutation

c.4018G>C

p.Glu1340Gln

p.E1340Q

Q9UPY3

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-D8-A27G-01

Breast

breast invasive 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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