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: DCTN1

Gene summary for DCTN1

Gene summary.

Gene information	Species	Human
	Gene symbol	DCTN1
	Gene ID	1639
	Gene name	dynactin subunit 1
	Gene Alias	DAP-150
	Cytomap	2p13.1
	Gene Type	protein-coding
	GO ID	GO:0000132
	UniProtAcc	Q14203

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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
1639	DCTN1	HTA11_3410_2000001011	Human	Colorectum	AD	1.41e-09	3.31e-01	0.0155
1639	DCTN1	HTA11_2487_2000001011	Human	Colorectum	SER	2.98e-09	5.40e-01	-0.1808
1639	DCTN1	HTA11_1938_2000001011	Human	Colorectum	AD	6.03e-09	4.47e-01	-0.0811
1639	DCTN1	HTA11_78_2000001011	Human	Colorectum	AD	8.02e-05	3.09e-01	-0.1088
1639	DCTN1	HTA11_347_2000001011	Human	Colorectum	AD	4.83e-15	4.55e-01	-0.1954
1639	DCTN1	HTA11_411_2000001011	Human	Colorectum	SER	2.61e-04	7.39e-01	-0.2602
1639	DCTN1	HTA11_3361_2000001011	Human	Colorectum	AD	3.23e-08	4.49e-01	-0.1207
1639	DCTN1	HTA11_83_2000001011	Human	Colorectum	SER	2.57e-02	3.42e-01	-0.1526
1639	DCTN1	HTA11_696_2000001011	Human	Colorectum	AD	1.47e-20	5.24e-01	-0.1464
1639	DCTN1	HTA11_866_2000001011	Human	Colorectum	AD	7.13e-07	2.92e-01	-0.1001
1639	DCTN1	HTA11_1391_2000001011	Human	Colorectum	AD	2.65e-12	5.73e-01	-0.059
1639	DCTN1	HTA11_2992_2000001011	Human	Colorectum	SER	2.41e-03	4.96e-01	-0.1706
1639	DCTN1	HTA11_546_2000001011	Human	Colorectum	AD	6.11e-05	4.79e-01	-0.0842
1639	DCTN1	HTA11_866_3004761011	Human	Colorectum	AD	3.62e-08	3.79e-01	0.096
1639	DCTN1	HTA11_8622_2000001021	Human	Colorectum	SER	2.55e-02	3.86e-01	0.0528
1639	DCTN1	HTA11_6801_2000001011	Human	Colorectum	SER	1.26e-02	4.07e-01	0.0171
1639	DCTN1	HTA11_10711_2000001011	Human	Colorectum	AD	3.61e-04	3.07e-01	0.0338
1639	DCTN1	HTA11_7696_3000711011	Human	Colorectum	AD	1.44e-17	5.21e-01	0.0674
1639	DCTN1	HTA11_99999970781_79442	Human	Colorectum	MSS	1.09e-09	3.59e-01	0.294
1639	DCTN1	HTA11_99999965104_69814	Human	Colorectum	MSS	3.09e-06	4.49e-01	0.281

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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
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:1902903	Colorectum	AD	regulation of supramolecular fiber organization	139/3918	383/18723	2.01e-12	3.19e-10	139
GO:0032271	Colorectum	AD	regulation of protein polymerization	94/3918	233/18723	1.01e-11	1.29e-09	94
GO:0051258	Colorectum	AD	protein polymerization	112/3918	297/18723	1.85e-11	2.27e-09	112
GO:0043254	Colorectum	AD	regulation of protein-containing complex assembly	148/3918	428/18723	2.64e-11	3.18e-09	148
GO:1902905	Colorectum	AD	positive regulation of supramolecular fiber organization	85/3918	209/18723	5.95e-11	6.33e-09	85
GO:0051495	Colorectum	AD	positive regulation of cytoskeleton organization	89/3918	226/18723	1.61e-10	1.56e-08	89
GO:0016197	Colorectum	AD	endosomal transport	90/3918	230/18723	1.88e-10	1.73e-08	90
GO:0032273	Colorectum	AD	positive regulation of protein polymerization	62/3918	138/18723	1.94e-10	1.76e-08	62
GO:0031334	Colorectum	AD	positive regulation of protein-containing complex assembly	91/3918	237/18723	4.78e-10	3.99e-08	91
GO:0022411	Colorectum	AD	cellular component disassembly	147/3918	443/18723	8.53e-10	6.76e-08	147
GO:0051656	Colorectum	AD	establishment of organelle localization	131/3918	390/18723	3.00e-09	2.06e-07	131
GO:0016482	Colorectum	AD	cytosolic transport	68/3918	168/18723	6.00e-09	3.72e-07	68
GO:0007163	Colorectum	AD	establishment or maintenance of cell polarity	77/3918	218/18723	5.72e-07	2.08e-05	77
GO:0042147	Colorectum	AD	retrograde transport, endosome to Golgi	37/3918	91/18723	1.46e-05	3.14e-04	37
GO:0106027	Colorectum	AD	neuron projection organization	36/3918	93/18723	6.58e-05	1.07e-03	36
GO:0030010	Colorectum	AD	establishment of cell polarity	50/3918	143/18723	6.90e-05	1.11e-03	50
GO:0060249	Colorectum	AD	anatomical structure homeostasis	94/3918	314/18723	9.37e-05	1.42e-03	94
GO:0043954	Colorectum	AD	cellular component maintenance	26/3918	61/18723	1.04e-04	1.56e-03	26
GO:0007051	Colorectum	AD	spindle organization	58/3918	184/18723	4.71e-04	5.20e-03	58
GO:1902850	Colorectum	AD	microtubule cytoskeleton organization involved in mitosis	48/3918	147/18723	5.87e-04	6.21e-03	48

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05016	Colorectum	AD	Huntington disease	147/2092	306/8465	1.93e-19	9.26e-18	5.91e-18	147
hsa05014	Colorectum	AD	Amyotrophic lateral sclerosis	164/2092	364/8465	4.28e-18	1.27e-16	8.09e-17	164
hsa05022	Colorectum	AD	Pathways of neurodegeneration - multiple diseases	201/2092	476/8465	4.54e-18	1.27e-16	8.09e-17	201
hsa05132	Colorectum	AD	Salmonella infection	102/2092	249/8465	7.65e-09	1.28e-07	8.17e-08	102
hsa04962	Colorectum	AD	Vasopressin-regulated water reabsorption	19/2092	44/8465	5.48e-03	2.48e-02	1.58e-02	19
hsa050161	Colorectum	AD	Huntington disease	147/2092	306/8465	1.93e-19	9.26e-18	5.91e-18	147
hsa050141	Colorectum	AD	Amyotrophic lateral sclerosis	164/2092	364/8465	4.28e-18	1.27e-16	8.09e-17	164
hsa050221	Colorectum	AD	Pathways of neurodegeneration - multiple diseases	201/2092	476/8465	4.54e-18	1.27e-16	8.09e-17	201
hsa051321	Colorectum	AD	Salmonella infection	102/2092	249/8465	7.65e-09	1.28e-07	8.17e-08	102
hsa049621	Colorectum	AD	Vasopressin-regulated water reabsorption	19/2092	44/8465	5.48e-03	2.48e-02	1.58e-02	19
hsa050162	Colorectum	SER	Huntington disease	127/1580	306/8465	3.29e-21	1.37e-19	9.92e-20	127
hsa050222	Colorectum	SER	Pathways of neurodegeneration - multiple diseases	168/1580	476/8465	6.23e-19	2.07e-17	1.50e-17	168
hsa050142	Colorectum	SER	Amyotrophic lateral sclerosis	138/1580	364/8465	9.89e-19	2.99e-17	2.17e-17	138
hsa051322	Colorectum	SER	Salmonella infection	77/1580	249/8465	1.56e-06	2.35e-05	1.71e-05	77
hsa050163	Colorectum	SER	Huntington disease	127/1580	306/8465	3.29e-21	1.37e-19	9.92e-20	127
hsa050223	Colorectum	SER	Pathways of neurodegeneration - multiple diseases	168/1580	476/8465	6.23e-19	2.07e-17	1.50e-17	168
hsa050143	Colorectum	SER	Amyotrophic lateral sclerosis	138/1580	364/8465	9.89e-19	2.99e-17	2.17e-17	138
hsa051323	Colorectum	SER	Salmonella infection	77/1580	249/8465	1.56e-06	2.35e-05	1.71e-05	77
hsa050164	Colorectum	MSS	Huntington disease	141/1875	306/8465	2.90e-21	1.62e-19	9.92e-20	141
hsa050224	Colorectum	MSS	Pathways of neurodegeneration - multiple diseases	192/1875	476/8465	2.79e-20	1.04e-18	6.36e-19	192

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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

DCTN1

SNV

Missense_Mutation

novel

c.2262G>C

p.Gln754His

p.Q754H

Q14203

protein_coding

tolerated(0.13)

probably_damaging(0.992)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

DCTN1

SNV

Missense_Mutation

rs761071126

c.1748G>A

p.Arg583Gln

p.R583Q

Q14203

protein_coding

tolerated(0.27)

probably_damaging(0.988)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

DCTN1

SNV

Missense_Mutation

novel

c.1492G>A

p.Glu498Lys

p.E498K

Q14203

protein_coding

deleterious(0.01)

probably_damaging(0.971)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

DCTN1

SNV

Missense_Mutation

rs146083590

c.3799N>C

p.Glu1267Gln

p.E1267Q

Q14203

protein_coding

tolerated(0.51)

benign(0.037)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DCTN1

SNV

Missense_Mutation

rs755766984

c.3788N>G

p.Val1263Gly

p.V1263G

Q14203

protein_coding

tolerated(0.1)

benign(0.42)

TCGA-B6-A0RN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

DCTN1

SNV

Missense_Mutation

rs145293019

c.2518N>A

p.Val840Met

p.V840M

Q14203

protein_coding

deleterious(0.01)

possibly_damaging(0.598)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

DCTN1

SNV

Missense_Mutation

rs376549770

c.3497N>T

p.Thr1166Met

p.T1166M

Q14203

protein_coding

tolerated(0.11)

benign(0.116)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DCTN1

SNV

Missense_Mutation

rs766620798

c.1850N>A

p.Cys617Tyr

p.C617Y

Q14203

protein_coding

tolerated(0.08)

probably_damaging(0.995)

TCGA-EW-A1P0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

DCTN1

insertion

Nonsense_Mutation

novel

c.3144_3145insTTGGGGCTTGTGTTTTGACCTTTGTCTAG

p.Arg1049LeufsTer6

p.R1049Lfs*6

Q14203

protein_coding

TCGA-A8-A09E-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

DCTN1

insertion

Nonsense_Mutation

novel

c.1305_1306insCACAACCTCCAGTAATCACATCACTACCCTTTCCCCA

p.Ala436HisfsTer5

p.A436Hfs*5

Q14203

protein_coding

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

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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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