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: TRAPPC12

Gene summary for TRAPPC12

Gene summary.

Gene information	Species	Human
	Gene symbol	TRAPPC12
	Gene ID	51112
	Gene name	trafficking protein particle complex subunit 12
	Gene Alias	CGI-87
	Cytomap	2p25.3
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	Q8WVT3

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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
51112	TRAPPC12	CCI_1	Human	Cervix	CC	4.17e-08	6.42e-01	0.528
51112	TRAPPC12	CCI_3	Human	Cervix	CC	9.28e-06	5.44e-01	0.516
51112	TRAPPC12	LZE7T	Human	Esophagus	ESCC	6.16e-04	1.38e-01	0.0667
51112	TRAPPC12	LZE8T	Human	Esophagus	ESCC	4.87e-03	1.06e-01	0.067
51112	TRAPPC12	LZE24T	Human	Esophagus	ESCC	8.36e-14	2.78e-01	0.0596
51112	TRAPPC12	LZE21T	Human	Esophagus	ESCC	1.48e-05	3.27e-01	0.0655
51112	TRAPPC12	P1T-E	Human	Esophagus	ESCC	1.19e-10	4.71e-01	0.0875
51112	TRAPPC12	P2T-E	Human	Esophagus	ESCC	7.12e-43	6.72e-01	0.1177
51112	TRAPPC12	P4T-E	Human	Esophagus	ESCC	1.98e-15	3.71e-01	0.1323
51112	TRAPPC12	P5T-E	Human	Esophagus	ESCC	5.83e-12	1.89e-01	0.1327
51112	TRAPPC12	P8T-E	Human	Esophagus	ESCC	8.98e-11	2.10e-01	0.0889
51112	TRAPPC12	P9T-E	Human	Esophagus	ESCC	5.44e-12	2.02e-01	0.1131
51112	TRAPPC12	P10T-E	Human	Esophagus	ESCC	2.86e-23	3.93e-01	0.116
51112	TRAPPC12	P11T-E	Human	Esophagus	ESCC	2.77e-15	5.91e-01	0.1426
51112	TRAPPC12	P12T-E	Human	Esophagus	ESCC	4.08e-14	2.85e-01	0.1122
51112	TRAPPC12	P15T-E	Human	Esophagus	ESCC	2.66e-11	2.66e-01	0.1149
51112	TRAPPC12	P16T-E	Human	Esophagus	ESCC	1.69e-12	1.22e-01	0.1153
51112	TRAPPC12	P17T-E	Human	Esophagus	ESCC	1.92e-09	2.76e-01	0.1278
51112	TRAPPC12	P20T-E	Human	Esophagus	ESCC	2.08e-12	2.35e-01	0.1124
51112	TRAPPC12	P21T-E	Human	Esophagus	ESCC	1.21e-10	1.66e-01	0.1617

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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:190382910	Cervix	CC	positive regulation of cellular protein localization	72/2311	276/18723	3.20e-10	4.46e-08	72
GO:004325410	Cervix	CC	regulation of protein-containing complex assembly	96/2311	428/18723	2.91e-09	3.05e-07	96
GO:00516567	Cervix	CC	establishment of organelle localization	76/2311	390/18723	3.17e-05	5.21e-04	76
GO:00481938	Cervix	CC	Golgi vesicle transport	58/2311	296/18723	2.24e-04	2.54e-03	58
GO:19021153	Cervix	CC	regulation of organelle assembly	40/2311	186/18723	2.92e-04	3.15e-03	40
GO:00070304	Cervix	CC	Golgi organization	32/2311	157/18723	2.78e-03	1.87e-02	32
GO:004819318	Esophagus	ESCC	Golgi vesicle transport	231/8552	296/18723	1.82e-30	9.63e-28	231
GO:005165617	Esophagus	ESCC	establishment of organelle localization	273/8552	390/18723	9.13e-23	1.81e-20	273
GO:1903829111	Esophagus	ESCC	positive regulation of cellular protein localization	199/8552	276/18723	2.99e-19	3.45e-17	199
GO:003304416	Esophagus	ESCC	regulation of chromosome organization	145/8552	187/18723	3.80e-19	4.31e-17	145
GO:000705911	Esophagus	ESCC	chromosome segregation	238/8552	346/18723	1.72e-18	1.82e-16	238
GO:0043254111	Esophagus	ESCC	regulation of protein-containing complex assembly	278/8552	428/18723	3.81e-16	2.77e-14	278
GO:000688815	Esophagus	ESCC	endoplasmic reticulum to Golgi vesicle-mediated transport	102/8552	130/18723	1.73e-14	9.22e-13	102
GO:005131011	Esophagus	ESCC	metaphase plate congression	58/8552	65/18723	1.81e-13	8.63e-12	58
GO:00988133	Esophagus	ESCC	nuclear chromosome segregation	187/8552	281/18723	1.00e-12	4.36e-11	187
GO:005130311	Esophagus	ESCC	establishment of chromosome localization	67/8552	80/18723	1.92e-12	8.09e-11	67
GO:005000011	Esophagus	ESCC	chromosome localization	68/8552	82/18723	3.37e-12	1.32e-10	68
GO:003450211	Esophagus	ESCC	protein localization to chromosome	70/8552	92/18723	2.54e-09	5.64e-08	70
GO:00070308	Esophagus	ESCC	Golgi organization	101/8552	157/18723	1.78e-06	2.10e-05	101
GO:190211514	Esophagus	ESCC	regulation of organelle assembly	116/8552	186/18723	3.15e-06	3.53e-05	116

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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

TRAPPC12

SNV

Missense_Mutation

novel

c.997G>A

p.Val333Met

p.V333M

Q8WVT3

protein_coding

tolerated(0.06)

possibly_damaging(0.584)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

TRAPPC12

SNV

Missense_Mutation

c.2104N>A

p.Glu702Lys

p.E702K

Q8WVT3

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-E2-A10C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

TRAPPC12

insertion

Nonsense_Mutation

novel

c.1936_1937insCTCCATCTAAAAAATAAAAATAAATAAAAAC

p.Ile646ThrfsTer6

p.I646Tfs*6

Q8WVT3

protein_coding

TCGA-A8-A0A1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

TRAPPC12

deletion

Frame_Shift_Del

novel

c.1384_1387delNNNN

p.Glu462ThrfsTer42

p.E462Tfs*42

Q8WVT3

protein_coding

TCGA-JL-A3YW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TRAPPC12

SNV

Missense_Mutation

novel

c.164C>T

p.Ser55Leu

p.S55L

Q8WVT3

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.994)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TRAPPC12

SNV

Missense_Mutation

novel

c.628T>C

p.Phe210Leu

p.F210L

Q8WVT3

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.932)

TCGA-DS-A1OA-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

carboplatin

TRAPPC12

SNV

Missense_Mutation

c.1819G>A

p.Glu607Lys

p.E607K

Q8WVT3

protein_coding

deleterious(0.04)

possibly_damaging(0.882)

TCGA-EK-A3GK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TRAPPC12

SNV

Missense_Mutation

c.1331N>T

p.Ala444Val

p.A444V

Q8WVT3

protein_coding

tolerated(0.05)

probably_damaging(0.917)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TRAPPC12

SNV

Missense_Mutation

novel

c.1872N>A

p.Met624Ile

p.M624I

Q8WVT3

protein_coding

tolerated(0.17)

benign(0.376)

TCGA-VS-A9UB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TRAPPC12

SNV

Missense_Mutation

rs368315810

c.1204N>T

p.Arg402Cys

p.R402C

Q8WVT3

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-A6-6781-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

oxaliplatin

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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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