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: NUP35

Gene summary for NUP35

Gene summary.

Gene information	Species	Human
	Gene symbol	NUP35
	Gene ID	129401
	Gene name	nucleoporin 35
	Gene Alias	MP-44
	Cytomap	2q32.1
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	Q8NFH5

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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
129401	NUP35	LZE4T	Human	Esophagus	ESCC	1.27e-03	2.72e-02	0.0811
129401	NUP35	LZE8T	Human	Esophagus	ESCC	3.34e-04	7.43e-02	0.067
129401	NUP35	LZE24T	Human	Esophagus	ESCC	2.55e-02	8.76e-02	0.0596
129401	NUP35	P2T-E	Human	Esophagus	ESCC	6.10e-20	2.68e-01	0.1177
129401	NUP35	P4T-E	Human	Esophagus	ESCC	3.35e-16	4.14e-01	0.1323
129401	NUP35	P5T-E	Human	Esophagus	ESCC	3.41e-11	1.87e-01	0.1327
129401	NUP35	P8T-E	Human	Esophagus	ESCC	2.01e-16	1.99e-01	0.0889
129401	NUP35	P9T-E	Human	Esophagus	ESCC	3.68e-06	3.82e-02	0.1131
129401	NUP35	P10T-E	Human	Esophagus	ESCC	6.37e-10	1.85e-01	0.116
129401	NUP35	P11T-E	Human	Esophagus	ESCC	1.93e-02	1.33e-01	0.1426
129401	NUP35	P12T-E	Human	Esophagus	ESCC	5.83e-19	3.94e-01	0.1122
129401	NUP35	P15T-E	Human	Esophagus	ESCC	8.53e-19	3.86e-01	0.1149
129401	NUP35	P16T-E	Human	Esophagus	ESCC	2.00e-14	1.99e-01	0.1153
129401	NUP35	P17T-E	Human	Esophagus	ESCC	6.60e-03	1.18e-01	0.1278
129401	NUP35	P20T-E	Human	Esophagus	ESCC	3.04e-16	1.69e-01	0.1124
129401	NUP35	P21T-E	Human	Esophagus	ESCC	4.99e-09	1.29e-01	0.1617
129401	NUP35	P22T-E	Human	Esophagus	ESCC	3.84e-07	5.31e-02	0.1236
129401	NUP35	P23T-E	Human	Esophagus	ESCC	1.39e-12	3.03e-01	0.108
129401	NUP35	P24T-E	Human	Esophagus	ESCC	1.17e-16	1.07e-01	0.1287
129401	NUP35	P26T-E	Human	Esophagus	ESCC	2.76e-11	1.93e-01	0.1276

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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
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

∗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:0072594110	Esophagus	ESCC	establishment of protein localization to organelle	311/8552	422/18723	3.02e-32	2.13e-29	311
GO:0006913110	Esophagus	ESCC	nucleocytoplasmic transport	230/8552	301/18723	6.04e-28	2.02e-25	230
GO:0051169110	Esophagus	ESCC	nuclear transport	230/8552	301/18723	6.04e-28	2.02e-25	230
GO:0006403110	Esophagus	ESCC	RNA localization	166/8552	201/18723	1.95e-27	6.18e-25	166
GO:003450418	Esophagus	ESCC	protein localization to nucleus	211/8552	290/18723	4.06e-21	6.60e-19	211
GO:005123617	Esophagus	ESCC	establishment of RNA localization	134/8552	166/18723	1.23e-20	1.81e-18	134
GO:005102815	Esophagus	ESCC	mRNA transport	110/8552	130/18723	2.76e-20	3.80e-18	110
GO:005065717	Esophagus	ESCC	nucleic acid transport	131/8552	163/18723	6.94e-20	8.46e-18	131
GO:005065817	Esophagus	ESCC	RNA transport	131/8552	163/18723	6.94e-20	8.46e-18	131
GO:001593117	Esophagus	ESCC	nucleobase-containing compound transport	162/8552	222/18723	9.87e-17	7.93e-15	162
GO:001703818	Esophagus	ESCC	protein import	149/8552	206/18723	5.90e-15	3.31e-13	149
GO:000699713	Esophagus	ESCC	nucleus organization	96/8552	133/18723	4.66e-10	1.21e-08	96
GO:005117014	Esophagus	ESCC	import into nucleus	111/8552	159/18723	5.69e-10	1.44e-08	111
GO:000660613	Esophagus	ESCC	protein import into nucleus	108/8552	155/18723	1.16e-09	2.77e-08	108
GO:00069994	Esophagus	ESCC	nuclear pore organization	14/8552	14/18723	1.71e-05	1.52e-04	14
GO:199082316	Esophagus	ESCC	response to leukemia inhibitory factor	60/8552	95/18723	4.41e-04	2.48e-03	60
GO:199083015	Esophagus	ESCC	cellular response to leukemia inhibitory factor	59/8552	94/18723	6.19e-04	3.32e-03	59
GO:007259418	Oral cavity	OSCC	establishment of protein localization to organelle	284/7305	422/18723	1.50e-32	1.35e-29	284
GO:000640318	Oral cavity	OSCC	RNA localization	150/7305	201/18723	6.90e-25	1.98e-22	150
GO:000691317	Oral cavity	OSCC	nucleocytoplasmic transport	204/7305	301/18723	2.65e-24	6.98e-22	204

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05014210	Esophagus	ESCC	Amyotrophic lateral sclerosis	266/4205	364/8465	1.31e-20	2.20e-18	1.13e-18	266
hsa0301321	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa0501438	Esophagus	ESCC	Amyotrophic lateral sclerosis	266/4205	364/8465	1.31e-20	2.20e-18	1.13e-18	266
hsa0301331	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa0501428	Oral cavity	OSCC	Amyotrophic lateral sclerosis	246/3704	364/8465	6.65e-21	1.11e-18	5.67e-19	246
hsa030136	Oral cavity	OSCC	Nucleocytoplasmic transport	82/3704	108/8465	7.93e-12	1.33e-10	6.77e-11	82
hsa05014112	Oral cavity	OSCC	Amyotrophic lateral sclerosis	246/3704	364/8465	6.65e-21	1.11e-18	5.67e-19	246
hsa0301311	Oral cavity	OSCC	Nucleocytoplasmic transport	82/3704	108/8465	7.93e-12	1.33e-10	6.77e-11	82
hsa0501429	Oral cavity	LP	Amyotrophic lateral sclerosis	197/2418	364/8465	1.25e-25	1.39e-23	8.93e-24	197
hsa030132	Oral cavity	LP	Nucleocytoplasmic transport	53/2418	108/8465	4.68e-06	4.10e-05	2.64e-05	53
hsa0501437	Oral cavity	LP	Amyotrophic lateral sclerosis	197/2418	364/8465	1.25e-25	1.39e-23	8.93e-24	197
hsa030133	Oral cavity	LP	Nucleocytoplasmic transport	53/2418	108/8465	4.68e-06	4.10e-05	2.64e-05	53

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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

NUP35

SNV

Missense_Mutation

c.542N>G

p.Phe181Cys

p.F181C

Q8NFH5

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A2-A04U-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

NUP35

SNV

Missense_Mutation

c.614N>A

p.Ser205Tyr

p.S205Y

Q8NFH5

protein_coding

deleterious(0.02)

possibly_damaging(0.775)

TCGA-BH-A201-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NUP35

SNV

Missense_Mutation

novel

c.514G>A

p.Asp172Asn

p.D172N

Q8NFH5

protein_coding

deleterious(0.04)

benign(0.086)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NUP35

SNV

Missense_Mutation

rs763888991

c.262N>A

p.Ala88Thr

p.A88T

Q8NFH5

protein_coding

deleterious(0)

probably_damaging(0.922)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NUP35

deletion

Frame_Shift_Del

c.927delN

p.Asp312MetfsTer26

p.D312Mfs*26

Q8NFH5

protein_coding

TCGA-A6-6653-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

NUP35

insertion

In_Frame_Ins

novel

c.843_844insCTGTTTATAAAC

p.Pro281_Arg282insLeuPheIleAsn

p.P281_R282insLFIN

Q8NFH5

protein_coding

TCGA-AM-5820-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

NUP35

SNV

Missense_Mutation

novel

c.682G>T

p.Asp228Tyr

p.D228Y

Q8NFH5

protein_coding

deleterious(0)

probably_damaging(0.972)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NUP35

SNV

Missense_Mutation

c.448N>A

p.Leu150Ile

p.L150I

Q8NFH5

protein_coding

tolerated(0.22)

benign(0.023)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

NUP35

SNV

Missense_Mutation

rs765515641

c.155N>A

p.Arg52Gln

p.R52Q

Q8NFH5

protein_coding

deleterious(0.03)

possibly_damaging(0.838)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NUP35

SNV

Missense_Mutation

novel

c.514G>A

p.Asp172Asn

p.D172N

Q8NFH5

protein_coding

deleterious(0.04)

benign(0.086)

TCGA-B5-A0JU-01

Endometrium

uterine corpus endometrioid carcinoma

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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