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: DCXR

Gene summary for DCXR

Gene summary.

Gene information	Species	Human
	Gene symbol	DCXR
	Gene ID	51181
	Gene name	dicarbonyl and L-xylulose reductase
	Gene Alias	DCR
	Cytomap	17q25.3
	Gene Type	protein-coding
	GO ID	GO:0005975
	UniProtAcc	Q7Z4W1

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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
51181	DCXR	GSM4909319	Human	Breast	IDC	2.50e-47	4.69e-01	0.1563
51181	DCXR	GSM4909320	Human	Breast	IDC	1.03e-23	6.65e-01	0.1575
51181	DCXR	GSM4909321	Human	Breast	IDC	1.86e-23	5.59e-01	0.1559
51181	DCXR	brca3	Human	Breast	Precancer	1.81e-03	-1.78e-01	-0.0263
51181	DCXR	NCCBC5	Human	Breast	DCIS	1.81e-03	-1.16e-01	0.2046
51181	DCXR	P1	Human	Breast	IDC	1.60e-07	-3.32e-01	0.1527
51181	DCXR	P2	Human	Breast	IDC	1.33e-13	5.16e-01	0.21
51181	DCXR	DCIS2	Human	Breast	DCIS	7.62e-56	6.37e-02	0.0085
51181	DCXR	HTA11_2487_2000001011	Human	Colorectum	SER	4.46e-02	2.39e-01	-0.1808
51181	DCXR	HTA11_1938_2000001011	Human	Colorectum	AD	5.62e-03	3.68e-01	-0.0811
51181	DCXR	HTA11_347_2000001011	Human	Colorectum	AD	1.10e-14	4.24e-01	-0.1954
51181	DCXR	HTA11_411_2000001011	Human	Colorectum	SER	7.66e-06	5.87e-01	-0.2602
51181	DCXR	HTA11_2112_2000001011	Human	Colorectum	SER	3.60e-02	4.90e-01	-0.2196
51181	DCXR	HTA11_3361_2000001011	Human	Colorectum	AD	2.41e-05	3.06e-01	-0.1207
51181	DCXR	HTA11_696_2000001011	Human	Colorectum	AD	2.90e-17	4.33e-01	-0.1464
51181	DCXR	HTA11_866_2000001011	Human	Colorectum	AD	8.12e-05	1.96e-01	-0.1001
51181	DCXR	HTA11_1391_2000001011	Human	Colorectum	AD	1.24e-08	3.61e-01	-0.059
51181	DCXR	HTA11_5216_2000001011	Human	Colorectum	SER	8.16e-06	6.09e-01	-0.1462
51181	DCXR	HTA11_546_2000001011	Human	Colorectum	AD	7.01e-07	4.11e-01	-0.0842
51181	DCXR	HTA11_10623_2000001011	Human	Colorectum	AD	2.23e-04	3.09e-01	-0.0177

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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
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
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:00725938	Breast	Precancer	reactive oxygen species metabolic process	30/1080	239/18723	5.13e-05	1.07e-03	30
GO:20003778	Breast	Precancer	regulation of reactive oxygen species metabolic process	20/1080	157/18723	7.19e-04	8.65e-03	20
GO:00060066	Breast	Precancer	glucose metabolic process	23/1080	196/18723	9.54e-04	1.07e-02	23
GO:00059966	Breast	Precancer	monosaccharide metabolic process	27/1080	257/18723	1.94e-03	1.88e-02	27
GO:00193186	Breast	Precancer	hexose metabolic process	25/1080	237/18723	2.64e-03	2.36e-02	25
GO:20003798	Breast	Precancer	positive regulation of reactive oxygen species metabolic process	11/1080	76/18723	4.08e-03	3.22e-02	11
GO:007259313	Breast	IDC	reactive oxygen species metabolic process	36/1434	239/18723	7.16e-05	1.43e-03	36
GO:200037913	Breast	IDC	positive regulation of reactive oxygen species metabolic process	14/1434	76/18723	1.71e-03	1.67e-02	14
GO:200037713	Breast	IDC	regulation of reactive oxygen species metabolic process	22/1434	157/18723	4.24e-03	3.31e-02	22
GO:007259322	Breast	DCIS	reactive oxygen species metabolic process	37/1390	239/18723	1.60e-05	3.88e-04	37
GO:200037922	Breast	DCIS	positive regulation of reactive oxygen species metabolic process	15/1390	76/18723	4.06e-04	5.54e-03	15
GO:200037723	Breast	DCIS	regulation of reactive oxygen species metabolic process	23/1390	157/18723	1.31e-03	1.37e-02	23
GO:000600612	Breast	DCIS	glucose metabolic process	25/1390	196/18723	5.59e-03	4.06e-02	25
GO:0019318	Colorectum	AD	hexose metabolic process	77/3918	237/18723	1.96e-05	4.01e-04	77
GO:0005996	Colorectum	AD	monosaccharide metabolic process	80/3918	257/18723	7.31e-05	1.17e-03	80
GO:0006006	Colorectum	AD	glucose metabolic process	62/3918	196/18723	2.76e-04	3.39e-03	62
GO:0072593	Colorectum	AD	reactive oxygen species metabolic process	73/3918	239/18723	2.79e-04	3.42e-03	73
GO:2000379	Colorectum	AD	positive regulation of reactive oxygen species metabolic process	29/3918	76/18723	4.31e-04	4.82e-03	29
GO:2000377	Colorectum	AD	regulation of reactive oxygen species metabolic process	48/3918	157/18723	2.77e-03	2.09e-02	48
GO:00725931	Colorectum	SER	reactive oxygen species metabolic process	61/2897	239/18723	3.63e-05	9.39e-04	61

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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

DCXR

insertion

Frame_Shift_Ins

novel

c.639_640insGAGATGCCCTCAGCACC

p.His214GlufsTer9

p.H214Efs*9

Q7Z4W1

protein_coding

TCGA-BH-A0BR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

DCXR

SNV

Missense_Mutation

novel

c.301N>A

p.Asp101Asn

p.D101N

Q7Z4W1

protein_coding

tolerated(0.06)

possibly_damaging(0.748)

TCGA-ZJ-AAXB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

DCXR

insertion

In_Frame_Ins

novel

c.513_513+1insTGCTCTACCTCT

p.Lys171_Ile172insCysSerThrSer

p.K171_I172insCSTS

Q7Z4W1

protein_coding

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

DCXR

SNV

Missense_Mutation

rs776627238

c.28N>T

p.Val10Leu

p.V10L

Q7Z4W1

protein_coding

deleterious(0.04)

benign(0.005)

TCGA-DM-A1HB-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Unknown

DCXR

SNV

Missense_Mutation

novel

c.398N>G

p.Asn133Ser

p.N133S

Q7Z4W1

protein_coding

deleterious(0.02)

probably_damaging(0.996)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

DCXR

SNV

Missense_Mutation

novel

c.639N>T

p.Glu213Asp

p.E213D

Q7Z4W1

protein_coding

tolerated(0.38)

benign(0)

TCGA-AJ-A3EL-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

DCXR

SNV

Missense_Mutation

c.573N>T

p.Trp191Cys

p.W191C

Q7Z4W1

protein_coding

deleterious(0)

probably_damaging(0.984)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

DCXR

SNV

Missense_Mutation

novel

c.173N>A

p.Cys58Tyr

p.C58Y

Q7Z4W1

protein_coding

tolerated(0.1)

benign(0.203)

TCGA-AX-A2HD-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

DCXR

SNV

Missense_Mutation

novel

c.599T>C

p.Met200Thr

p.M200T

Q7Z4W1

protein_coding

deleterious(0)

possibly_damaging(0.756)

TCGA-EO-A22U-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

DCXR

SNV

Missense_Mutation

novel

c.158G>A

p.Gly53Glu

p.G53E

Q7Z4W1

protein_coding

tolerated(0.13)

benign(0.18)

TCGA-EO-A3AY-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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