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: TRIM38

Gene summary for TRIM38

Gene summary.

Gene information	Species	Human
	Gene symbol	TRIM38
	Gene ID	10475
	Gene name	tripartite motif containing 38
	Gene Alias	RNF15
	Cytomap	6p22.2
	Gene Type	protein-coding
	GO ID	GO:0000209
	UniProtAcc	A0A024QZY4

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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
10475	TRIM38	LZE4T	Human	Esophagus	ESCC	2.08e-03	1.06e-01	0.0811
10475	TRIM38	LZE5T	Human	Esophagus	ESCC	5.11e-05	2.11e-01	0.0514
10475	TRIM38	LZE7T	Human	Esophagus	ESCC	8.58e-05	2.54e-01	0.0667
10475	TRIM38	LZE8T	Human	Esophagus	ESCC	5.86e-08	1.68e-01	0.067
10475	TRIM38	LZE20T	Human	Esophagus	ESCC	3.00e-02	1.54e-01	0.0662
10475	TRIM38	LZE21D1	Human	Esophagus	HGIN	3.66e-03	3.59e-01	0.0632
10475	TRIM38	LZE24T	Human	Esophagus	ESCC	7.86e-10	4.32e-01	0.0596
10475	TRIM38	LZE21T	Human	Esophagus	ESCC	4.44e-05	3.93e-01	0.0655
10475	TRIM38	LZE6T	Human	Esophagus	ESCC	1.20e-03	1.23e-01	0.0845
10475	TRIM38	P1T-E	Human	Esophagus	ESCC	1.06e-10	4.88e-01	0.0875
10475	TRIM38	P2T-E	Human	Esophagus	ESCC	1.64e-42	7.30e-01	0.1177
10475	TRIM38	P4T-E	Human	Esophagus	ESCC	1.45e-11	3.57e-01	0.1323
10475	TRIM38	P5T-E	Human	Esophagus	ESCC	8.06e-03	5.60e-02	0.1327
10475	TRIM38	P8T-E	Human	Esophagus	ESCC	6.55e-17	3.35e-01	0.0889
10475	TRIM38	P9T-E	Human	Esophagus	ESCC	1.43e-20	4.66e-01	0.1131
10475	TRIM38	P10T-E	Human	Esophagus	ESCC	6.17e-08	1.04e-01	0.116
10475	TRIM38	P11T-E	Human	Esophagus	ESCC	9.08e-09	3.81e-01	0.1426
10475	TRIM38	P12T-E	Human	Esophagus	ESCC	9.77e-12	2.23e-01	0.1122
10475	TRIM38	P15T-E	Human	Esophagus	ESCC	2.46e-09	2.14e-01	0.1149
10475	TRIM38	P16T-E	Human	Esophagus	ESCC	1.73e-07	8.98e-02	0.1153

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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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:003133120	Oral cavity	OSCC	positive regulation of cellular catabolic process	273/7305	427/18723	6.39e-26	2.02e-23	273
GO:001905820	Oral cavity	OSCC	viral life cycle	208/7305	317/18723	4.59e-22	1.00e-19	208
GO:001050610	Oral cavity	OSCC	regulation of autophagy	198/7305	317/18723	1.63e-17	1.51e-15	198
GO:000020910	Oral cavity	OSCC	protein polyubiquitination	150/7305	236/18723	1.59e-14	9.27e-13	150
GO:004312218	Oral cavity	OSCC	regulation of I-kappaB kinase/NF-kappaB signaling	155/7305	249/18723	7.79e-14	4.14e-12	155
GO:004312310	Oral cavity	OSCC	positive regulation of I-kappaB kinase/NF-kappaB signaling	122/7305	186/18723	1.68e-13	8.52e-12	122
GO:000724910	Oral cavity	OSCC	I-kappaB kinase/NF-kappaB signaling	169/7305	281/18723	4.69e-13	2.25e-11	169
GO:004440320	Oral cavity	OSCC	biological process involved in symbiotic interaction	173/7305	290/18723	6.80e-13	3.19e-11	173
GO:005079220	Oral cavity	OSCC	regulation of viral process	109/7305	164/18723	8.95e-13	4.10e-11	109
GO:190390020	Oral cavity	OSCC	regulation of viral life cycle	97/7305	148/18723	5.34e-11	1.67e-09	97
GO:005170120	Oral cavity	OSCC	biological process involved in interaction with host	125/7305	203/18723	5.60e-11	1.74e-09	125
GO:004852417	Oral cavity	OSCC	positive regulation of viral process	51/7305	65/18723	9.56e-11	2.90e-09	51
GO:005212620	Oral cavity	OSCC	movement in host environment	106/7305	175/18723	5.84e-09	1.26e-07	106
GO:00105087	Oral cavity	OSCC	positive regulation of autophagy	77/7305	124/18723	1.59e-07	2.61e-06	77
GO:00510907	Oral cavity	OSCC	regulation of DNA-binding transcription factor activity	221/7305	440/18723	9.06e-07	1.23e-05	221
GO:004440920	Oral cavity	OSCC	entry into host	86/7305	151/18723	5.74e-06	6.37e-05	86
GO:004671820	Oral cavity	OSCC	viral entry into host cell	81/7305	144/18723	1.98e-05	1.89e-04	81
GO:00510917	Oral cavity	OSCC	positive regulation of DNA-binding transcription factor activity	134/7305	260/18723	2.52e-05	2.35e-04	134
GO:19039029	Oral cavity	OSCC	positive regulation of viral life cycle	22/7305	29/18723	6.05e-05	4.95e-04	22
GO:004390319	Oral cavity	OSCC	regulation of biological process involved in symbiotic interaction	44/7305	72/18723	1.20e-04	8.57e-04	44

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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

TRIM38

SNV

Missense_Mutation

c.87N>G

p.Ile29Met

p.I29M

O00635

protein_coding

deleterious(0)

possibly_damaging(0.782)

TCGA-A2-A0EQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

TRIM38

SNV

Missense_Mutation

novel

c.844N>A

p.Asp282Asn

p.D282N

O00635

protein_coding

tolerated(0.12)

benign(0.173)

TCGA-AR-A250-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

TRIM38

SNV

Missense_Mutation

c.826G>T

p.Val276Phe

p.V276F

O00635

protein_coding

deleterious(0.02)

probably_damaging(0.916)

TCGA-BH-A0AZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

TRIM38

insertion

Nonsense_Mutation

novel

c.1308_1309insACATGTTGTTAGAAGAGCTGAAGCAGGACTGGCTTG

p.Thr436_Phe437insThrCysCysTerLysSerTerSerArgThrGlyLeu

p.T436_F437insTCC*KS*SRTGL

O00635

protein_coding

TCGA-A8-A0A1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

TRIM38

deletion

In_Frame_Del

novel

c.1367_1369delNNN

p.Pro457del

p.P457del

O00635

protein_coding

TCGA-BH-A0DQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

TRIM38

SNV

Missense_Mutation

rs368108856

c.1072G>A

p.Gly358Arg

p.G358R

O00635

protein_coding

tolerated(0.4)

benign(0.35)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TRIM38

SNV

Missense_Mutation

rs758236250

c.145N>G

p.Gln49Glu

p.Q49E

O00635

protein_coding

tolerated(0.35)

benign(0.039)

TCGA-DS-A1OC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

gemcitabine

TRIM38

insertion

In_Frame_Ins

novel

c.788_789insGGT

p.Ser263_Glu264insVal

p.S263_E264insV

O00635

protein_coding

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

TRIM38

SNV

Missense_Mutation

novel

c.772N>A

p.Val258Met

p.V258M

O00635

protein_coding

tolerated(0.46)

benign(0.03)

TCGA-AA-3947-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

TRIM38

SNV

Missense_Mutation

c.726N>T

p.Gln242His

p.Q242H

O00635

protein_coding

deleterious(0.04)

possibly_damaging(0.808)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

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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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