PXD050416

PXD050416 is an original dataset announced via ProteomeXchange.

Title	Proteomics-derived biomarker panel facilitates distinguishing primary lung adenocarcinomas with intestinal or mucinous differentiation (PAIM) from lung metastatic colorectal cancer (lmCRC)
Description	The diagnosis of primary lung adenocarcinomas with intestinal or mucinous differentiation (PAIM) remains challenging due to the overlapping histomorphological, immunohistochemical and genetic characteristics with lung metastatic colorectal cancer (lmCRC). This study aimed to explore the protein biomarkers that could distinguish between PAIM and lmCRC. To uncover differences between the two diseases, we used tandem mass tagging (TMT)-based shotgun proteomics to characterize proteomes of formalin-fixed paraffin-embedded (FFPE) tumor samples of PAIM (n = 22) and lmCRC (n = 17). Then three machine learning algorithms, namely support vector machine (SVM), random forest and the Least Absolute Shrinkage and Selection Operator (LASSO), were utilized to select protein features with diagnostic significance. These candidate proteins were further validated in an independent cohort (PAIM, n = 11; lmCRC, n = 19) by immunochemistry (IHC) to confirm their diagnostic performance. In total, 105 proteins out of 7871 proteins were significantly dysregulated between PAIM and lmCRC samples and well-separated two groups by Uniform Manifold Approximation and Projection (UMAP). The upregulated proteins in PAIM were involved in actin cytoskeleton organization, platelet degranulation, and regulation of leukocyte chemotaxis, while downregulated ones were involved in mitochondrial transmembrane transport, vasculature development, and stem cell proliferation. A set of 10 candidate proteins (high-level expression in lmCRC: CDH17, ATP1B3, GLB1, OXNAD1, LYST, FABP1; high-level expression in PAIM: NARR, MLPH, S100A14, CK7) was ultimately selected to distinguish PAIM from lmCRC by machine learning algorithms. We further confirmed using IHC that the five protein biomarkers including CDH17, CK7, MLPH, FABP1 and NARR were effective biomarkers for distinguishing PAIM from lmCRC. Our study depicts PAIM-specific proteomic characteristics and demonstrates the potential utility of new protein biomarkers for the differential diagnosis of PAIM and lmCRC. These findings may contribute to improving the diagnostic accuracy and guide appropriate treatments for these patients.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:47:04.111.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tiannan Guo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-06 13:13:37	ID requested
1	2024-06-23 01:58:44	announced
⏵ 2	2024-10-22 06:47:04	announced	2024-10-22: Updated project metadata.

10.1016/j.mcpro.2024.100766;

submitter keyword: primary lung adenocarcinomas

intestinal or mucinous differentiation

lung metastatic colorectal cancer

proteomics

Tiannan Guo
contact affiliation	School of Life Sciences, Westlake University, Hangzhou, Zhejiang Province, China
contact email	guotiannan@westlake.edu.cn
lab head
Tiannan Guo
contact affiliation	Westlake University
contact email	guotiannan@westlake.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD050416
     1. Label: PRIDE project
     2. Name: Proteomics-derived biomarker panel facilitates distinguishing primary lung adenocarcinomas with intestinal or mucinous differentiation (PAIM) from lung metastatic colorectal cancer (lmCRC)