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: LARP4B

Gene summary for LARP4B

Gene summary.

Gene information	Species	Human
	Gene symbol	LARP4B
	Gene ID	23185
	Gene name	La ribonucleoprotein 4B
	Gene Alias	KIAA0217
	Cytomap	10p15.3
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	Q92615

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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
23185	LARP4B	CCI_1	Human	Cervix	CC	7.96e-10	9.39e-01	0.528
23185	LARP4B	CCI_2	Human	Cervix	CC	1.78e-16	1.63e+00	0.5249
23185	LARP4B	CCI_3	Human	Cervix	CC	2.42e-12	8.88e-01	0.516
23185	LARP4B	HTA11_347_2000001011	Human	Colorectum	AD	1.70e-08	4.93e-01	-0.1954
23185	LARP4B	HTA11_99999965104_69814	Human	Colorectum	MSS	1.18e-06	5.32e-01	0.281
23185	LARP4B	HTA11_99999974143_84620	Human	Colorectum	MSS	6.67e-03	-3.60e-01	0.3005
23185	LARP4B	A001-C-207	Human	Colorectum	FAP	1.57e-03	-2.28e-01	0.1278
23185	LARP4B	A015-C-203	Human	Colorectum	FAP	3.02e-33	-4.06e-01	-0.1294
23185	LARP4B	A015-C-204	Human	Colorectum	FAP	6.68e-05	-2.47e-01	-0.0228
23185	LARP4B	A014-C-040	Human	Colorectum	FAP	9.61e-04	-1.97e-01	-0.1184
23185	LARP4B	A002-C-201	Human	Colorectum	FAP	2.39e-11	-2.28e-01	0.0324
23185	LARP4B	A001-C-119	Human	Colorectum	FAP	4.67e-06	-4.20e-01	-0.1557
23185	LARP4B	A001-C-108	Human	Colorectum	FAP	4.79e-17	-3.48e-01	-0.0272
23185	LARP4B	A002-C-205	Human	Colorectum	FAP	3.99e-25	-3.57e-01	-0.1236
23185	LARP4B	A001-C-104	Human	Colorectum	FAP	3.47e-03	-2.02e-01	0.0184
23185	LARP4B	A015-C-006	Human	Colorectum	FAP	7.72e-19	-3.79e-01	-0.0994
23185	LARP4B	A015-C-106	Human	Colorectum	FAP	1.95e-12	-2.17e-01	-0.0511
23185	LARP4B	A002-C-114	Human	Colorectum	FAP	2.67e-22	-3.89e-01	-0.1561
23185	LARP4B	A015-C-104	Human	Colorectum	FAP	9.56e-34	-4.66e-01	-0.1899
23185	LARP4B	A001-C-014	Human	Colorectum	FAP	1.42e-14	-3.05e-01	0.0135

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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
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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
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
Prostate		BPH: Benign Prostatic Hyperplasia
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:003133010	Cervix	CC	negative regulation of cellular catabolic process	63/2311	262/18723	1.10e-07	5.68e-06	63
GO:00064029	Cervix	CC	mRNA catabolic process	56/2311	232/18723	4.81e-07	1.83e-05	56
GO:19033119	Cervix	CC	regulation of mRNA metabolic process	64/2311	288/18723	1.71e-06	5.64e-05	64
GO:000989510	Cervix	CC	negative regulation of catabolic process	69/2311	320/18723	2.15e-06	6.55e-05	69
GO:00064019	Cervix	CC	RNA catabolic process	62/2311	278/18723	2.18e-06	6.56e-05	62
GO:003425010	Cervix	CC	positive regulation of cellular amide metabolic process	40/2311	162/18723	1.11e-05	2.41e-04	40
GO:000641710	Cervix	CC	regulation of translation	89/2311	468/18723	1.86e-05	3.46e-04	89
GO:004572710	Cervix	CC	positive regulation of translation	33/2311	136/18723	9.09e-05	1.20e-03	33
GO:00610139	Cervix	CC	regulation of mRNA catabolic process	38/2311	166/18723	1.07e-04	1.36e-03	38
GO:190331210	Cervix	CC	negative regulation of mRNA metabolic process	24/2311	92/18723	2.49e-04	2.77e-03	24
GO:00467008	Cervix	CC	heterocycle catabolic process	80/2311	445/18723	3.23e-04	3.42e-03	80
GO:00346559	Cervix	CC	nucleobase-containing compound catabolic process	74/2311	407/18723	3.77e-04	3.88e-03	74
GO:00434889	Cervix	CC	regulation of mRNA stability	35/2311	158/18723	3.80e-04	3.89e-03	35
GO:00434879	Cervix	CC	regulation of RNA stability	36/2311	170/18723	7.72e-04	6.86e-03	36
GO:00442709	Cervix	CC	cellular nitrogen compound catabolic process	79/2311	451/18723	7.80e-04	6.91e-03	79
GO:19023698	Cervix	CC	negative regulation of RNA catabolic process	19/2311	75/18723	1.54e-03	1.19e-02	19
GO:00194398	Cervix	CC	aromatic compound catabolic process	79/2311	467/18723	2.14e-03	1.54e-02	79
GO:19013618	Cervix	CC	organic cyclic compound catabolic process	80/2311	495/18723	6.77e-03	3.72e-02	80
GO:19023738	Cervix	CC	negative regulation of mRNA catabolic process	15/2311	63/18723	8.52e-03	4.40e-02	15
GO:1903311	Colorectum	AD	regulation of mRNA metabolic process	117/3918	288/18723	1.69e-14	4.23e-12	117

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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

LARP4B

SNV

Missense_Mutation

c.1148G>T

p.Gly383Val

p.G383V

Q92615

protein_coding

deleterious(0.01)

benign(0.231)

TCGA-A2-A0CS-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

LARP4B

SNV

Missense_Mutation

novel

c.792N>G

p.Phe264Leu

p.F264L

Q92615

protein_coding

deleterious(0.05)

probably_damaging(0.997)

TCGA-A8-A06O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

LARP4B

SNV

Missense_Mutation

c.895T>C

p.Phe299Leu

p.F299L

Q92615

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-E2-A154-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

LARP4B

SNV

Missense_Mutation

c.1285C>G

p.Pro429Ala

p.P429A

Q92615

protein_coding

tolerated(0.44)

benign(0.001)

TCGA-EW-A1OY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

LARP4B

deletion

Frame_Shift_Del

novel

c.793delN

p.Ile265Ter

p.I265*

Q92615

protein_coding

TCGA-A8-A06O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

LARP4B

insertion

Frame_Shift_Ins

novel

c.614_615insATCAC

p.Asp206SerfsTer6

p.D206Sfs*6

Q92615

protein_coding

TCGA-AR-A251-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

LARP4B

SNV

Missense_Mutation

novel

c.100N>G

p.Gln34Glu

p.Q34E

Q92615

protein_coding

tolerated_low_confidence(0.32)

benign(0)

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

LARP4B

SNV

Missense_Mutation

c.817N>A

p.Asp273Asn

p.D273N

Q92615

protein_coding

tolerated(0.31)

probably_damaging(1)

TCGA-IR-A3LI-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

LARP4B

SNV

Missense_Mutation

c.532T>C

p.Tyr178His

p.Y178H

Q92615

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AA-3672-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

LARP4B

SNV

Missense_Mutation

rs199947494

c.2174N>A

p.Arg725His

p.R725H

Q92615

protein_coding

deleterious(0.03)

benign(0.01)

TCGA-AA-3821-01

Colorectum

colon adenocarcinoma

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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