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: MAN1B1

Gene summary for MAN1B1

Gene summary.

Gene information	Species	Human
	Gene symbol	MAN1B1
	Gene ID	11253
	Gene name	mannosidase alpha class 1B member 1
	Gene Alias	ERMAN1
	Cytomap	9q34.3
	Gene Type	protein-coding
	GO ID	GO:0005975
	UniProtAcc	Q9UKM7

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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
11253	MAN1B1	LZE4T	Human	Esophagus	ESCC	1.27e-03	2.10e-01	0.0811
11253	MAN1B1	LZE7T	Human	Esophagus	ESCC	5.44e-08	4.45e-01	0.0667
11253	MAN1B1	LZE8T	Human	Esophagus	ESCC	1.27e-05	2.25e-01	0.067
11253	MAN1B1	LZE20T	Human	Esophagus	ESCC	5.21e-08	4.47e-01	0.0662
11253	MAN1B1	LZE24T	Human	Esophagus	ESCC	7.17e-13	3.30e-01	0.0596
11253	MAN1B1	LZE21T	Human	Esophagus	ESCC	9.28e-03	4.09e-01	0.0655
11253	MAN1B1	P1T-E	Human	Esophagus	ESCC	8.66e-14	5.39e-01	0.0875
11253	MAN1B1	P2T-E	Human	Esophagus	ESCC	5.70e-42	6.73e-01	0.1177
11253	MAN1B1	P4T-E	Human	Esophagus	ESCC	6.16e-20	4.31e-01	0.1323
11253	MAN1B1	P5T-E	Human	Esophagus	ESCC	4.31e-18	3.18e-01	0.1327
11253	MAN1B1	P8T-E	Human	Esophagus	ESCC	7.13e-46	6.31e-01	0.0889
11253	MAN1B1	P9T-E	Human	Esophagus	ESCC	6.15e-13	2.71e-01	0.1131
11253	MAN1B1	P10T-E	Human	Esophagus	ESCC	2.64e-26	3.96e-01	0.116
11253	MAN1B1	P11T-E	Human	Esophagus	ESCC	1.75e-20	9.98e-01	0.1426
11253	MAN1B1	P12T-E	Human	Esophagus	ESCC	5.56e-21	3.82e-01	0.1122
11253	MAN1B1	P15T-E	Human	Esophagus	ESCC	3.18e-21	4.83e-01	0.1149
11253	MAN1B1	P16T-E	Human	Esophagus	ESCC	6.68e-36	5.37e-01	0.1153
11253	MAN1B1	P17T-E	Human	Esophagus	ESCC	8.09e-17	7.30e-01	0.1278
11253	MAN1B1	P19T-E	Human	Esophagus	ESCC	1.19e-04	5.63e-01	0.1662
11253	MAN1B1	P20T-E	Human	Esophagus	ESCC	6.71e-16	1.77e-01	0.1124

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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
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:001908011	Liver	Cirrhotic	viral gene expression	52/4634	94/18723	2.19e-10	1.08e-08	52
GO:0030433	Liver	Cirrhotic	ubiquitin-dependent ERAD pathway	45/4634	85/18723	2.19e-08	7.75e-07	45
GO:00365032	Liver	Cirrhotic	ERAD pathway	53/4634	107/18723	2.58e-08	8.89e-07	53
GO:00065171	Liver	Cirrhotic	protein deglycosylation	14/4634	26/18723	1.37e-03	9.14e-03	14
GO:00190824	Liver	Cirrhotic	viral protein processing	15/4634	29/18723	1.59e-03	1.03e-02	15
GO:00365071	Liver	Cirrhotic	protein demannosylation	10/4634	18/18723	5.00e-03	2.59e-02	10
GO:00365081	Liver	Cirrhotic	protein alpha-1,2-demannosylation	10/4634	18/18723	5.00e-03	2.59e-02	10
GO:001049822	Liver	HCC	proteasomal protein catabolic process	351/7958	490/18723	6.92e-40	1.46e-36	351
GO:004316122	Liver	HCC	proteasome-mediated ubiquitin-dependent protein catabolic process	299/7958	412/18723	7.82e-36	8.27e-33	299
GO:001603222	Liver	HCC	viral process	286/7958	415/18723	4.41e-28	1.86e-25	286
GO:003497612	Liver	HCC	response to endoplasmic reticulum stress	189/7958	256/18723	1.43e-24	4.06e-22	189
GO:003650311	Liver	HCC	ERAD pathway	88/7958	107/18723	2.87e-17	2.85e-15	88
GO:00304331	Liver	HCC	ubiquitin-dependent ERAD pathway	72/7958	85/18723	9.78e-16	7.47e-14	72
GO:001908021	Liver	HCC	viral gene expression	77/7958	94/18723	4.33e-15	3.12e-13	77
GO:00065172	Liver	HCC	protein deglycosylation	22/7958	26/18723	1.23e-05	1.39e-04	22
GO:001908211	Liver	HCC	viral protein processing	23/7958	29/18723	5.86e-05	5.38e-04	23
GO:1901136	Liver	HCC	carbohydrate derivative catabolic process	98/7958	172/18723	8.71e-05	7.62e-04	98
GO:00064862	Liver	HCC	protein glycosylation	122/7958	226/18723	3.11e-04	2.21e-03	122
GO:00434132	Liver	HCC	macromolecule glycosylation	122/7958	226/18723	3.11e-04	2.21e-03	122
GO:00700852	Liver	HCC	glycosylation	128/7958	240/18723	4.35e-04	2.92e-03	128

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04141211	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa0051023	Esophagus	ESCC	N-Glycan biosynthesis	39/4205	53/8465	3.26e-04	1.15e-03	5.89e-04	39
hsa005136	Esophagus	ESCC	Various types of N-glycan biosynthesis	31/4205	42/8465	1.23e-03	3.78e-03	1.93e-03	31
hsa04141310	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa0051033	Esophagus	ESCC	N-Glycan biosynthesis	39/4205	53/8465	3.26e-04	1.15e-03	5.89e-04	39
hsa0051313	Esophagus	ESCC	Various types of N-glycan biosynthesis	31/4205	42/8465	1.23e-03	3.78e-03	1.93e-03	31
hsa0414114	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114
hsa005104	Liver	Cirrhotic	N-Glycan biosynthesis	32/2530	53/8465	3.82e-06	4.10e-05	2.53e-05	32
hsa005134	Liver	Cirrhotic	Various types of N-glycan biosynthesis	26/2530	42/8465	1.65e-05	1.41e-04	8.69e-05	26
hsa0414115	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114
hsa0051011	Liver	Cirrhotic	N-Glycan biosynthesis	32/2530	53/8465	3.82e-06	4.10e-05	2.53e-05	32
hsa0051311	Liver	Cirrhotic	Various types of N-glycan biosynthesis	26/2530	42/8465	1.65e-05	1.41e-04	8.69e-05	26
hsa0414122	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0051021	Liver	HCC	N-Glycan biosynthesis	40/4020	53/8465	2.95e-05	1.87e-04	1.04e-04	40
hsa005132	Liver	HCC	Various types of N-glycan biosynthesis	30/4020	42/8465	1.41e-03	5.07e-03	2.82e-03	30
hsa0414132	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0051031	Liver	HCC	N-Glycan biosynthesis	40/4020	53/8465	2.95e-05	1.87e-04	1.04e-04	40
hsa005133	Liver	HCC	Various types of N-glycan biosynthesis	30/4020	42/8465	1.41e-03	5.07e-03	2.82e-03	30
hsa0414130	Oral cavity	OSCC	Protein processing in endoplasmic reticulum	143/3704	174/8465	6.82e-26	2.28e-23	1.16e-23	143
hsa005105	Oral cavity	OSCC	N-Glycan biosynthesis	39/3704	53/8465	9.77e-06	4.36e-05	2.22e-05	39

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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

MAN1B1

SNV

Missense_Mutation

novel

c.1607N>A

p.Gly536Asp

p.G536D

Q9UKM7

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-3C-AAAU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

zoladex

MAN1B1

SNV

Missense_Mutation

c.1919N>T

p.Ser640Phe

p.S640F

Q9UKM7

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MAN1B1

SNV

Missense_Mutation

c.376N>A

p.Ala126Thr

p.A126T

Q9UKM7

protein_coding

tolerated(0.28)

benign(0)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

MAN1B1

SNV

Missense_Mutation

c.988G>C

p.Glu330Gln

p.E330Q

Q9UKM7

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-E2-A159-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

MAN1B1

SNV

Missense_Mutation

c.1857G>T

p.Trp619Cys

p.W619C

Q9UKM7

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-GM-A2DB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

MAN1B1

insertion

Frame_Shift_Ins

novel

c.763_764insTTTCGCGATGTTGGCGAGGCTGGTCTCAA

p.Asp255ValfsTer30

p.D255Vfs*30

Q9UKM7

protein_coding

TCGA-AQ-A04J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

MAN1B1

insertion

Nonsense_Mutation

novel

c.765_766insTTCTGACCTCAG

p.Asp255_Val256insPheTerProGln

p.D255_V256insF*PQ

Q9UKM7

protein_coding

TCGA-AQ-A04J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

MAN1B1

insertion

In_Frame_Ins

novel

c.885_886insCCAAAAAAATTTAAAAAAAGGGAACGAAGGGACTGTAGC

p.Leu295_Asp296insProLysLysPheLysLysArgGluArgArgAspCysSer

p.L295_D296insPKKFKKRERRDCS

Q9UKM7

protein_coding

TCGA-BH-A0B4-01

Breast

breast invasive carcinoma

Male

>=65

III/IV

Hormone Therapy

tamoxiphen

MAN1B1

SNV

Missense_Mutation

c.880N>A

p.Ala294Thr

p.A294T

Q9UKM7

protein_coding

deleterious(0)

probably_damaging(0.945)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MAN1B1

SNV

Missense_Mutation

rs775259244

c.1474N>A

p.Glu492Lys

p.E492K

Q9UKM7

protein_coding

tolerated(0.23)

benign(0.041)

TCGA-2W-A8YY-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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