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Gene & Protein in Disease Prognostic potential of LMNB2 in LPS

1. Introduction involvement before DNA fragmentation. 21,22 The nuclear
events of apoptosis involve lamin cleavage and inactivation,
Liposarcoma (LPS), a malignant mesenchymal tumor as well as the cleavage of structural protein Gas2, which is
arising from adipocytes, accounts for approximately involved in actin microfilament reorganization and DNA
15 – 20% of soft tissue sarcomas (STS) and ranks as the fragmentation. Therefore, inhibiting lamin cleavage alone
second most common subtype following gastrointestinal is insufficient to block apoptosis, but it can promote nuclear
1,2
stromal tumors. LPS is a diagnostically challenging decomposition and accelerate apoptosis 21,22 (Figure 1).
STS due to its diverse histological subtypes, with patient
prognosis and treatment strategies depending on the It has been reported that the abnormal expression, gene
histological subtype. The five major histopathological mutation, or abnormal localization of LMNB2 can affect
subtypes of LPS include well-differentiated LPS (WDLPS), the nuclear scaffold structure, leading to changes in nuclear
dedifferentiated LPS (DDLPS), myxoid LPS (MLPS), morphology and dysfunction, 11,12,23 ultimately contributing to
pleomorphic LPS (PLPS), and myxoid pleomorphic cancer cell migration and metastasis. 11,15,24,25 The expression
LPS. Given the clinicopathologic discrepancies among level of LMNB2 has been correlated with the prognosis of
3,4
20
these histological subtypes, an in-depth exploration of tumors, including primary colorectal cancer, hepatocellular
16
26
their clinical manifestation, treatment sensitivity, and carcinoma, non-small cell lung cancer, triple-negative
28
27
underlying pathogenesis is imperative to guide targeted breast cancer, and bladder cancer. However, it remains
therapy strategies aimed at improving patient survival. At unclear whether LMNB2 exhibits significant expression
2,5
present, complete surgical resection with clear margins is changes in LPS tissues, and the correlation between LMNB2
the most effective treatment modality for LPS. In addition, and LPS prognosis requires exploration.
radiotherapy reduces the risk of high-grade recurrence, In this study, the differential expression patterns and
while chemotherapy mitigates subtypes with metastatic prognostic significances of LMNB2 in LPS were analyzed
potential, albeit without enhanced outcomes for drug- to identify its potential as a biomarker for LPS patients.
resistant DDLPS subtypes. In recent years, there has Our findings indicate that elevated expression of LMNB2
6-8
been significantly increased widespread attention given is a common feature in LPS and is associated with shorter
to the development of new drugs for targeted therapies, survival time for LPS patients. Thus, LMNB2 emerges as
including exportin 1 inhibitors and PPARγ agonists. a potential prognostic biomarker and promising therapy
2,8
Targeting murine double minute 2 or/and cyclin- target for LPS.
dependent kinases 4 has been proven to be a promising
therapy strategy for LPS patients. Given the high 2. Methods
2,9
molecular heterogeneity inherent in LPS, the identification 2.1. Data download and collation
of additional biomarkers as potential therapeutic targets is
crucial for the development of effective treatment options The flowchart illustrating the study’s methodology is
and the improvement of patient survival time. illustrated in Figure 2. Expression profiling and survival
data of LPS patients were obtained from The Cancer
Lamin B2, a member of the lamin family, is encoded Genome Atlas (TCGA [https://portal.gdc.cancer.gov/]).
10
by the LMNB2 gene located on chromosome 19p13.3. This dataset encompassed crucial information, including
Lamins, categorized as V-shaped intermediate filament survival time, age, gender, clinical stage, and Tumor,
proteins, 11-13 predominantly constitute the nuclear lamina, Nodes, and Metastasis stage for 60 LPS patients. In
serving as a fundamental structural component. 13,14 addition, expression profiling data from the GSE159659
Integral to the organization and functionality of the and GSE21122 datasets were collected from the Gene
nucleus, lamins mediate the connections between the Expression Omnibus (GEO) database. These datasets
inner nuclear skeleton and the peripheral lamina, ensuring comprised different subtypes of normal and tumor
stability and morphological maintenance while facilitating samples. Specifically, GSE159659 contained 15 normal
signal transduction, transcription regulation, nuclear pore samples, 15 DDLPS samples, and 15 WDLPS samples,
anchoring, and chromatin regulation. 13,15-17 Lamin B2 is while the GSE21122 dataset contained nine normal and
implicated in a variety of cellular processes, including cell 149 LPS samples. Furthermore, the GSE30929 dataset
cycle control and apoptosis. 12,14,18,19 Considered a key anti- included 140 tumor samples.
apoptotic protein, Lamin B2 also participates in chromatin
17
epigenetic regulation, nuclear membrane breakage, and 2.2. Differential expression analysis of microarray
recombination events during mitosis. While Lamin B2 is data by GEO2R
20
cleaved by caspase-6, leading to its inactivation (Figure 1), GEO2R (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi)
increased expression delays cell death, proving its is an interactive web tool used for comparing gene

Volume 3 Issue 1 (2024) 2 https://doi.org/10.36922/gpd.2607