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: TMTC3

Gene summary for TMTC3

Gene summary.

Gene information	Species	Human
	Gene symbol	TMTC3
	Gene ID	160418
	Gene name	transmembrane O-mannosyltransferase targeting cadherins 3
	Gene Alias	LIS8
	Cytomap	12q21.32
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	A8K321

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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
160418	TMTC3	LZE2T	Human	Esophagus	ESCC	3.15e-07	6.74e-01	0.082
160418	TMTC3	LZE4T	Human	Esophagus	ESCC	7.81e-20	6.80e-01	0.0811
160418	TMTC3	LZE7T	Human	Esophagus	ESCC	1.04e-04	5.83e-01	0.0667
160418	TMTC3	LZE8T	Human	Esophagus	ESCC	1.78e-04	3.42e-01	0.067
160418	TMTC3	LZE24T	Human	Esophagus	ESCC	1.26e-10	2.47e-01	0.0596
160418	TMTC3	P1T-E	Human	Esophagus	ESCC	1.46e-03	3.35e-01	0.0875
160418	TMTC3	P2T-E	Human	Esophagus	ESCC	1.06e-59	9.07e-01	0.1177
160418	TMTC3	P4T-E	Human	Esophagus	ESCC	4.04e-16	4.55e-01	0.1323
160418	TMTC3	P5T-E	Human	Esophagus	ESCC	1.59e-10	2.45e-01	0.1327
160418	TMTC3	P8T-E	Human	Esophagus	ESCC	4.05e-16	3.36e-01	0.0889
160418	TMTC3	P9T-E	Human	Esophagus	ESCC	3.08e-08	2.08e-01	0.1131
160418	TMTC3	P10T-E	Human	Esophagus	ESCC	2.89e-28	4.69e-01	0.116
160418	TMTC3	P11T-E	Human	Esophagus	ESCC	7.91e-10	6.74e-01	0.1426
160418	TMTC3	P12T-E	Human	Esophagus	ESCC	1.90e-18	3.78e-01	0.1122
160418	TMTC3	P15T-E	Human	Esophagus	ESCC	9.54e-24	6.81e-01	0.1149
160418	TMTC3	P16T-E	Human	Esophagus	ESCC	3.14e-15	3.27e-01	0.1153
160418	TMTC3	P20T-E	Human	Esophagus	ESCC	5.28e-25	3.79e-01	0.1124
160418	TMTC3	P21T-E	Human	Esophagus	ESCC	3.17e-35	7.95e-01	0.1617
160418	TMTC3	P22T-E	Human	Esophagus	ESCC	2.68e-26	4.98e-01	0.1236
160418	TMTC3	P23T-E	Human	Esophagus	ESCC	5.51e-23	6.75e-01	0.108

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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:0010498111	Esophagus	ESCC	proteasomal protein catabolic process	369/8552	490/18723	1.13e-41	1.80e-38	369
GO:0042176111	Esophagus	ESCC	regulation of protein catabolic process	280/8552	391/18723	8.65e-26	2.39e-23	280
GO:0009896111	Esophagus	ESCC	positive regulation of catabolic process	332/8552	492/18723	4.36e-23	9.22e-21	332
GO:0034976111	Esophagus	ESCC	response to endoplasmic reticulum stress	192/8552	256/18723	7.15e-22	1.30e-19	192
GO:0031331111	Esophagus	ESCC	positive regulation of cellular catabolic process	292/8552	427/18723	8.67e-22	1.53e-19	292
GO:1903362111	Esophagus	ESCC	regulation of cellular protein catabolic process	188/8552	255/18723	5.12e-20	6.62e-18	188
GO:0045862111	Esophagus	ESCC	positive regulation of proteolysis	256/8552	372/18723	7.88e-20	9.43e-18	256
GO:1903050111	Esophagus	ESCC	regulation of proteolysis involved in cellular protein catabolic process	163/8552	221/18723	1.44e-17	1.27e-15	163
GO:0061136111	Esophagus	ESCC	regulation of proteasomal protein catabolic process	142/8552	187/18723	2.40e-17	2.00e-15	142
GO:0045732111	Esophagus	ESCC	positive regulation of protein catabolic process	167/8552	231/18723	1.47e-16	1.14e-14	167
GO:1903364111	Esophagus	ESCC	positive regulation of cellular protein catabolic process	117/8552	155/18723	3.25e-14	1.66e-12	117
GO:1901800110	Esophagus	ESCC	positive regulation of proteasomal protein catabolic process	91/8552	114/18723	6.74e-14	3.34e-12	91
GO:1903052110	Esophagus	ESCC	positive regulation of proteolysis involved in cellular protein catabolic process	101/8552	133/18723	9.58e-13	4.19e-11	101
GO:00091002	Esophagus	ESCC	glycoprotein metabolic process	226/8552	387/18723	2.64e-07	3.94e-06	226
GO:00700854	Esophagus	ESCC	glycosylation	144/8552	240/18723	5.12e-06	5.38e-05	144
GO:00064865	Esophagus	ESCC	protein glycosylation	135/8552	226/18723	1.36e-05	1.24e-04	135
GO:00434135	Esophagus	ESCC	macromolecule glycosylation	135/8552	226/18723	1.36e-05	1.24e-04	135
GO:00091012	Esophagus	ESCC	glycoprotein biosynthetic process	181/8552	317/18723	2.54e-05	2.15e-04	181
GO:00064931	Esophagus	ESCC	protein O-linked glycosylation	51/8552	86/18723	7.54e-03	2.70e-02	51
GO:001049822	Liver	HCC	proteasomal protein catabolic process	351/7958	490/18723	6.92e-40	1.46e-36	351

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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

TMTC3

SNV

Missense_Mutation

c.1492N>C

p.Glu498Gln

p.E498Q

Q6ZXV5

protein_coding

tolerated(0.09)

possibly_damaging(0.785)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TMTC3

SNV

Missense_Mutation

novel

c.2245N>A

p.Gln749Lys

p.Q749K

Q6ZXV5

protein_coding

tolerated(0.73)

benign(0.007)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TMTC3

SNV

Missense_Mutation

c.2668A>G

p.Ile890Val

p.I890V

Q6ZXV5

protein_coding

tolerated_low_confidence(0.08)

benign(0.028)

TCGA-B6-A0IB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

TMTC3

SNV

Missense_Mutation

novel

c.1042N>C

p.Val348Leu

p.V348L

Q6ZXV5

protein_coding

tolerated(0.49)

benign(0.046)

TCGA-EW-A6SB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TMTC3

SNV

Missense_Mutation

rs768991210

c.235N>T

p.Arg79Cys

p.R79C

Q6ZXV5

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TMTC3

SNV

Missense_Mutation

c.91N>C

p.Asp31His

p.D31H

Q6ZXV5

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-EK-A3GK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TMTC3

SNV

Missense_Mutation

rs764794677

c.2356N>C

p.Asp786His

p.D786H

Q6ZXV5

protein_coding

deleterious(0.05)

possibly_damaging(0.532)

TCGA-IR-A3LH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TMTC3

SNV

Missense_Mutation

novel

c.604N>A

p.Glu202Lys

p.E202K

Q6ZXV5

protein_coding

deleterious(0)

probably_damaging(0.939)

TCGA-ZJ-AAXD-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

TMTC3

SNV

Missense_Mutation

novel

c.2073N>A

p.Met691Ile

p.M691I

Q6ZXV5

protein_coding

tolerated(0.1)

benign(0.006)

TCGA-ZJ-AAXU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TMTC3

deletion

Frame_Shift_Del

novel

c.1856delA

p.Asn619ThrfsTer8

p.N619Tfs*8

Q6ZXV5

protein_coding

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

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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