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: MISP

Gene summary for MISP

Gene summary.

Gene information	Species	Human
	Gene symbol	MISP
	Gene ID	126353
	Gene name	mitotic spindle positioning
	Gene Alias	C19orf21
	Cytomap	19p13.3
	Gene Type	protein-coding
	GO ID	GO:0000132
	UniProtAcc	Q8IVT2

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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
126353	MISP	HTA11_6818_2000001011	Human	Colorectum	AD	1.99e-03	3.48e-01	0.0112
126353	MISP	HTA11_11156_2000001011	Human	Colorectum	AD	2.52e-03	3.24e-01	0.0397
126353	MISP	HTA11_6818_2000001021	Human	Colorectum	AD	8.08e-03	1.43e-01	0.0588
126353	MISP	HTA11_99999965104_69814	Human	Colorectum	MSS	9.99e-08	5.21e-01	0.281
126353	MISP	HTA11_99999971662_82457	Human	Colorectum	MSS	3.48e-05	2.64e-01	0.3859
126353	MISP	HTA11_99999973899_84307	Human	Colorectum	MSS	1.09e-09	6.72e-01	0.2585
126353	MISP	CRC-3-11773	Human	Colorectum	CRC	3.56e-02	3.69e-01	0.2564
126353	MISP	LZE5T	Human	Esophagus	ESCC	2.34e-05	5.04e-01	0.0514
126353	MISP	LZE7T	Human	Esophagus	ESCC	8.75e-04	2.73e-01	0.0667
126353	MISP	LZE22T	Human	Esophagus	ESCC	4.55e-03	3.52e-01	0.068
126353	MISP	LZE24T	Human	Esophagus	ESCC	4.60e-15	7.45e-01	0.0596
126353	MISP	P1T-E	Human	Esophagus	ESCC	2.04e-03	5.30e-01	0.0875
126353	MISP	P2T-E	Human	Esophagus	ESCC	4.62e-02	8.61e-02	0.1177
126353	MISP	P4T-E	Human	Esophagus	ESCC	7.94e-06	1.92e-01	0.1323
126353	MISP	P5T-E	Human	Esophagus	ESCC	9.29e-04	1.09e-01	0.1327
126353	MISP	P8T-E	Human	Esophagus	ESCC	5.96e-22	4.68e-01	0.0889
126353	MISP	P12T-E	Human	Esophagus	ESCC	1.62e-03	1.04e-01	0.1122
126353	MISP	P21T-E	Human	Esophagus	ESCC	1.02e-03	1.60e-01	0.1617
126353	MISP	P22T-E	Human	Esophagus	ESCC	3.06e-04	1.34e-01	0.1236
126353	MISP	P23T-E	Human	Esophagus	ESCC	1.41e-30	1.27e+00	0.108

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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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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:1990778	Colorectum	AD	protein localization to cell periphery	129/3918	333/18723	5.51e-14	1.15e-11	129
GO:0051656	Colorectum	AD	establishment of organelle localization	131/3918	390/18723	3.00e-09	2.06e-07	131
GO:1904375	Colorectum	AD	regulation of protein localization to cell periphery	54/3918	125/18723	1.52e-08	9.00e-07	54
GO:0007163	Colorectum	AD	establishment or maintenance of cell polarity	77/3918	218/18723	5.72e-07	2.08e-05	77
GO:0030010	Colorectum	AD	establishment of cell polarity	50/3918	143/18723	6.90e-05	1.11e-03	50
GO:0007051	Colorectum	AD	spindle organization	58/3918	184/18723	4.71e-04	5.20e-03	58
GO:1902850	Colorectum	AD	microtubule cytoskeleton organization involved in mitosis	48/3918	147/18723	5.87e-04	6.21e-03	48
GO:0090307	Colorectum	AD	mitotic spindle assembly	25/3918	65/18723	9.12e-04	8.71e-03	25
GO:0007052	Colorectum	AD	mitotic spindle organization	40/3918	120/18723	1.03e-03	9.61e-03	40
GO:0051660	Colorectum	AD	establishment of centrosome localization	7/3918	10/18723	1.15e-03	1.04e-02	7
GO:0051225	Colorectum	AD	spindle assembly	37/3918	117/18723	4.32e-03	2.96e-02	37
GO:0140014	Colorectum	AD	mitotic nuclear division	78/3918	287/18723	6.48e-03	4.05e-02	78
GO:19907781	Colorectum	SER	protein localization to cell periphery	98/2897	333/18723	6.09e-11	9.57e-09	98
GO:00516561	Colorectum	SER	establishment of organelle localization	100/2897	390/18723	1.11e-07	6.79e-06	100
GO:19043751	Colorectum	SER	regulation of protein localization to cell periphery	40/2897	125/18723	2.85e-06	1.16e-04	40
GO:00071631	Colorectum	SER	establishment or maintenance of cell polarity	60/2897	218/18723	3.45e-06	1.33e-04	60
GO:00300101	Colorectum	SER	establishment of cell polarity	37/2897	143/18723	8.72e-04	1.06e-02	37
GO:19907782	Colorectum	MSS	protein localization to cell periphery	120/3467	333/18723	2.02e-14	5.47e-12	120
GO:19043752	Colorectum	MSS	regulation of protein localization to cell periphery	51/3467	125/18723	5.46e-09	3.55e-07	51
GO:00516562	Colorectum	MSS	establishment of organelle localization	115/3467	390/18723	7.30e-08	3.67e-06	115

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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

MISP

SNV

Missense_Mutation

rs140196930

c.1169N>A

p.Arg390Gln

p.R390Q

Q8IVT2

protein_coding

tolerated(0.14)

benign(0.037)

TCGA-A2-A3KC-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

MISP

SNV

Missense_Mutation

novel

c.1609A>T

p.Arg537Trp

p.R537W

Q8IVT2

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-A8-A08R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MISP

SNV

Missense_Mutation

rs775079741

c.1225G>A

p.Asp409Asn

p.D409N

Q8IVT2

protein_coding

tolerated(0.22)

benign(0.027)

TCGA-LL-A5YN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

MISP

insertion

In_Frame_Ins

novel

c.1988_1989insTAGGAA

p.Ala663_Met664insArgAsn

p.A663_M664insRN

Q8IVT2

protein_coding

TCGA-A8-A0A4-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

MISP

insertion

Frame_Shift_Ins

novel

c.1990_1991insTAGGAATGTGCCACTGCACCCAGATAGTTTATTTTTAT

p.Met664IlefsTer57

p.M664Ifs*57

Q8IVT2

protein_coding

TCGA-A8-A0A4-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

MISP

insertion

Nonsense_Mutation

novel

c.1899_1900insGGACTACAGGCGCCTGCCTCCACGCCTGGCTAATTTTTTTGT

p.Lys633_Lys634insGlyLeuGlnAlaProAlaSerThrProGlyTerPhePheCys

p.K633_K634insGLQAPASTPG*FFC

Q8IVT2

protein_coding

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

MISP

SNV

Missense_Mutation

novel

c.1691N>C

p.Glu564Ala

p.E564A

Q8IVT2

protein_coding

deleterious(0)

possibly_damaging(0.841)

TCGA-DS-A1OD-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MISP

SNV

Missense_Mutation

c.503G>T

p.Gly168Val

p.G168V

Q8IVT2

protein_coding

tolerated(0.33)

benign(0.01)

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MISP

SNV

Missense_Mutation

novel

c.1747G>C

p.Asp583His

p.D583H

Q8IVT2

protein_coding

deleterious(0.04)

possibly_damaging(0.503)

TCGA-JW-A5VJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MISP

SNV

Missense_Mutation

c.1787N>A

p.Thr596Lys

p.T596K

Q8IVT2

protein_coding

tolerated(0.06)

probably_damaging(0.927)

TCGA-LP-A4AW-01

Cervix

cervical & endocervical cancer

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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