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: NUCB1

Gene summary for NUCB1

Gene summary.

Gene information	Species	Human
	Gene symbol	NUCB1
	Gene ID	4924
	Gene name	nucleobindin 1
	Gene Alias	CALNUC
	Cytomap	19q13.33
	Gene Type	protein-coding
	GO ID	GO:0006605
	UniProtAcc	A8K7Q1

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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
4924	NUCB1	P12T-E	Human	Esophagus	ESCC	2.23e-32	8.18e-01	0.1122
4924	NUCB1	P15T-E	Human	Esophagus	ESCC	7.47e-44	1.26e+00	0.1149
4924	NUCB1	P16T-E	Human	Esophagus	ESCC	9.07e-35	9.66e-01	0.1153
4924	NUCB1	P17T-E	Human	Esophagus	ESCC	9.94e-26	1.34e+00	0.1278
4924	NUCB1	P19T-E	Human	Esophagus	ESCC	1.90e-16	1.27e+00	0.1662
4924	NUCB1	P20T-E	Human	Esophagus	ESCC	1.05e-17	5.29e-01	0.1124
4924	NUCB1	P21T-E	Human	Esophagus	ESCC	8.72e-70	1.48e+00	0.1617
4924	NUCB1	P22T-E	Human	Esophagus	ESCC	5.24e-61	1.33e+00	0.1236
4924	NUCB1	P23T-E	Human	Esophagus	ESCC	2.34e-45	1.33e+00	0.108
4924	NUCB1	P24T-E	Human	Esophagus	ESCC	9.26e-48	1.14e+00	0.1287
4924	NUCB1	P26T-E	Human	Esophagus	ESCC	1.95e-63	1.43e+00	0.1276
4924	NUCB1	P27T-E	Human	Esophagus	ESCC	4.60e-40	1.12e+00	0.1055
4924	NUCB1	P28T-E	Human	Esophagus	ESCC	2.73e-32	9.15e-01	0.1149
4924	NUCB1	P30T-E	Human	Esophagus	ESCC	1.44e-37	1.78e+00	0.137
4924	NUCB1	P31T-E	Human	Esophagus	ESCC	1.81e-53	1.17e+00	0.1251
4924	NUCB1	P32T-E	Human	Esophagus	ESCC	1.41e-83	1.93e+00	0.1666
4924	NUCB1	P36T-E	Human	Esophagus	ESCC	6.28e-30	1.17e+00	0.1187
4924	NUCB1	P37T-E	Human	Esophagus	ESCC	6.14e-43	1.11e+00	0.1371
4924	NUCB1	P38T-E	Human	Esophagus	ESCC	4.03e-02	1.95e-01	0.127
4924	NUCB1	P39T-E	Human	Esophagus	ESCC	5.38e-11	2.74e-01	0.0894

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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
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:0006605	Colorectum	AD	protein targeting	105/3918	314/18723	1.39e-07	6.44e-06	105
GO:0032386	Colorectum	AD	regulation of intracellular transport	109/3918	337/18723	5.33e-07	1.95e-05	109
GO:0033157	Colorectum	AD	regulation of intracellular protein transport	80/3918	229/18723	5.81e-07	2.09e-05	80
GO:1903533	Colorectum	AD	regulation of protein targeting	31/3918	81/18723	2.61e-04	3.25e-03	31
GO:00331571	Colorectum	SER	regulation of intracellular protein transport	68/2897	229/18723	3.41e-08	2.30e-06	68
GO:00323861	Colorectum	SER	regulation of intracellular transport	89/2897	337/18723	1.34e-07	7.96e-06	89
GO:00066051	Colorectum	SER	protein targeting	76/2897	314/18723	3.19e-05	8.47e-04	76
GO:19035331	Colorectum	SER	regulation of protein targeting	24/2897	81/18723	9.20e-04	1.11e-02	24
GO:00066052	Colorectum	MSS	protein targeting	97/3467	314/18723	6.76e-08	3.46e-06	97
GO:00331572	Colorectum	MSS	regulation of intracellular protein transport	76/3467	229/18723	7.03e-08	3.56e-06	76
GO:00323862	Colorectum	MSS	regulation of intracellular transport	102/3467	337/18723	9.73e-08	4.71e-06	102
GO:19035332	Colorectum	MSS	regulation of protein targeting	28/3467	81/18723	4.34e-04	5.23e-03	28
GO:00066053	Colorectum	MSI-H	protein targeting	44/1319	314/18723	9.50e-06	4.55e-04	44
GO:00323863	Colorectum	MSI-H	regulation of intracellular transport	46/1319	337/18723	1.20e-05	5.48e-04	46
GO:00331573	Colorectum	MSI-H	regulation of intracellular protein transport	33/1319	229/18723	6.86e-05	2.29e-03	33
GO:00323865	Colorectum	CRC	regulation of intracellular transport	61/2078	337/18723	7.94e-05	1.65e-03	61
GO:00331575	Colorectum	CRC	regulation of intracellular protein transport	45/2078	229/18723	9.62e-05	1.95e-03	45
GO:00066055	Colorectum	CRC	protein targeting	54/2078	314/18723	7.17e-04	9.28e-03	54
GO:000660525	Esophagus	HGIN	protein targeting	78/2587	314/18723	1.08e-07	5.47e-06	78
GO:003238617	Esophagus	HGIN	regulation of intracellular transport	79/2587	337/18723	1.11e-06	4.36e-05	79

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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

NUCB1

SNV

Missense_Mutation

c.822N>C

p.Glu274Asp

p.E274D

Q02818

protein_coding

tolerated(0.21)

probably_damaging(0.936)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NUCB1

SNV

Missense_Mutation

c.1249N>C

p.Glu417Gln

p.E417Q

Q02818

protein_coding

tolerated(0.27)

benign(0)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NUCB1

insertion

Frame_Shift_Ins

novel

c.879_880insGAAATTAACCACTGGATTTGCAAGATGAGGGTTC

p.Leu294GlufsTer69

p.L294Efs*69

Q02818

protein_coding

TCGA-AN-A0FN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NUCB1

SNV

Missense_Mutation

c.1078N>C

p.Glu360Gln

p.E360Q

Q02818

protein_coding

deleterious(0.04)

possibly_damaging(0.844)

TCGA-C5-A1ME-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NUCB1

SNV

Missense_Mutation

c.1314N>C

p.Gln438His

p.Q438H

Q02818

protein_coding

deleterious(0.03)

benign(0.005)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

NUCB1

SNV

Missense_Mutation

rs749759537

c.64N>T

p.Arg22Cys

p.R22C

Q02818

protein_coding

tolerated(0.15)

benign(0.129)

TCGA-EX-A69L-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NUCB1

SNV

Missense_Mutation

novel

c.421C>A

p.Leu141Met

p.L141M

Q02818

protein_coding

deleterious(0.01)

probably_damaging(0.921)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

NUCB1

SNV

Missense_Mutation

novel

c.937N>G

p.Thr313Ala

p.T313A

Q02818

protein_coding

deleterious(0.01)

possibly_damaging(0.715)

TCGA-A5-A2K3-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

carboplatin

NUCB1

SNV

Missense_Mutation

rs375589971

c.457G>A

p.Asp153Asn

p.D153N

Q02818

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AJ-A3OK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

carboplatin

NUCB1

SNV

Missense_Mutation

novel

c.986C>T

p.Thr329Ile

p.T329I

Q02818

protein_coding

deleterious(0.04)

benign(0.007)

TCGA-AP-A1DP-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

paclitaxel

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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
4924	NUCB1	DRUGGABLE GENOME	antagonist	252166902
4924	NUCB1	DRUGGABLE GENOME		GS-5734	REMDESIVIR
4924	NUCB1	DRUGGABLE GENOME	antagonist	252166718

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