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Proteomics analysis of different histologic subtypes of lung adenocarcinoma reveals a critical role of LRPAP1 in micropapillary pattern metastasis

ABSTRACT: Lung adenocarcinomas differ in prognosis based on their histologic growth pattern. Micropapillary growth in lung adenocarcinoma is associated with a host of adverse prognostic factors, especially metastases. Metastasis is the major cause of high mortality in lung cancer. Exploring the underlying mechanisms of metastasis in the early stage thus holds promise for identifying new therapeutic strategies that may enhance survival. We applied quantitative mass spectrometry to compare protein expression profiles in different histologic subtypes, including adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), invasive adenocarcinoma (IAC) histologic subtype includes acinar (ACI), micropapillary (MIP). We discovered that low-density lipoprotein receptor–related protein–associated protein 1 (LRPAP1) has the highest protein level in MIP, which was confirmed by immunohistochemistry (IHC). The co-expressed proteins in our data like PSMD1 and HSP90AB1 were also reported they are high-expressed in cancer and have important role in metastasis. Overexpressed LRPAP1 promoted migration of lung cancer cells in vitro. Our findings suggest that LRPAP1 plays an important role in promoting lung cancer cell metastasis, and may act as a novel target for anti-metastatic therapy.

ORGANISM(S): Homo Sapiens

SUBMITTER: Furong Li

PROVIDER: PXD038594 | iProX | Wed Dec 07 00:00:00 GMT 2022

REPOSITORIES: iProX

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Proteomic analysis reveals LRPAP1 as a key player in the micropapillary pattern metastasis of lung adenocarcinoma.

Yan Hao-Jie HJ Lin Sheng-Cheng SC Xu Shao-Hang SH Gao Yu-Biao YB Zhou Bao-Jin BJ Zhou Ruo R Chen Fu-Ming FM Li Fu-Rong FR

Heliyon 20231220 1

<h4>Objectives</h4>Lung adenocarcinomas have different prognoses depending on their histological growth patterns. Micropapillary growth within lung adenocarcinoma, particularly metastasis, is related to dismal prognostic outcome. Metastasis accounts for a major factor leading to mortality among lung cancer patients. Understanding the mechanisms underlying early stage metastasis can help develop novel treatments for improving patient survival.<h4>Methods</h4>Here, quantitative mass spectrometry w ...[more]

PMID: 38226250

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Project description:Background: JAG-1 is a ligand of Notch signaling and can regulate cell differentiation and proliferation in cancers. Recent studies indicated that JAG1 is a gene associated with cancer progression. Therefore, we investigated the role of JAG1 in lung cancer progression. Methods: The expression of JAG1 was manipulated by overexpression or RNA silencing in several human lung cell lines. The effect of JAG1 on tumorigenesis and invasion was assessed by the cell anchorage-independent growth, cell proliferation, cell migration and invasion assays in vitro as well as metastasis in vivo. The potential downstream genes of JAG1 were identified by oligonucleotide microarrays and quantitative reverse transcriptionÂ¡Vpolymerase chain reaction (RT-PCR). We further measured JAG1 expression in lung cancer specimens by RT-PCR. Correlation between JAG1 expression and overall survival of lung cancer patients was determined by using the log-rank test and multivariable Cox proportional hazards regression analysis. All statistical tests were two-sided. Results: JAG1 enhanced anchorage-independent growth, cell migration, invasion in the lower invasive cells, CL1-0. JAG1 also increased the capability of migration and invasion in the other two lung cancer cell lines (A549 and NCI-H226). The silencing of JAG1 inhibited migration and invasion activities of the higher invasive cells, CL1-5, by siRNA technology. The invasion-promoting activity of JAG1 was also demonstrated in vivo by using a mouse metastasis model. By microarray analysis, we found that the expression of heat shock 70kDa protein 2 (HSPA2) was activated by JAG1 overexpression and eliminated by JAG1 silencing. Moreover, lung cancer patients with high JAG1 expressing tumors had shorter overall survival than those with low-expressing tumors. Conclusion: JAG1 might be an oncogene which promotes colonogenesis and metastasis, and high JAG1 expression is associated with shorten survival in lung cancer. In this investigation, we used a lung cancer invasion cell model to identify the genes involved in cancer progression. JAG1 is a potential oncogene whose expression is correlated to the survival of patients with breast, prostate and liver cancers. However, the role of JAG1 in lung caner progression has not been reported, particularly in metastasis. Here, JAG1 was ectopically expressed in lower invasive lung cancer cell line its impact on colonogenesis, migration and invasiveness was assessed. The underlying mechanism was explored by JAG1-expressed transfectants and microarrays and the clinical relevance was evaluated by quantitative RT-PCR.

Dataset Information

Proteomics analysis of different histologic subtypes of lung adenocarcinoma reveals a critical role of LRPAP1 in micropapillary pattern metastasis

Publications

Proteomic analysis reveals LRPAP1 as a key player in the micropapillary pattern metastasis of lung adenocarcinoma.

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