Expression of the Stem Cell Factor Nestin in Malignant Pleural Mesothelioma Is Associated with Poor Prognosis

Thies, Svenja; Friess, Martina; Frischknecht, Lukas; Korol, Dimitri; Felley‐Bosco, Emanuela; Stahel, Rolf A.; Vrugt, Bart; Weder, Walter; Opitz, Isabelle; Soltermann, Alex

doi:10.1371/journal.pone.0139312

Cited by 10 publications

(13 citation statements)

References 31 publications

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“…Expression of cancer stem cell markers has been reported in malignant mesotheliomas, and such expression seemed to be associated with a more malignant phenotype in vitro [9,15]. Among the cancer stem cell markers, only Nestin, a type VI intermediate filament protein, was immunohistochemically analyzed for its prognostic impact on mesothelioma patients [16].…”

Section: Introductionmentioning

confidence: 99%

Expression of ALCAM (CD166) and PD-L1 (CD274) independently predicts shorter survival in malignant pleural mesothelioma

et al. 2018

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Diffuse malignant mesothelioma of the pleura is a highly aggressive tumor typically associated with short survival. ALCAM (CD166), a type I transmembrane protein, is a member of the immunoglobulin superfamily. In normal cells, ALCAM regulates physiological processes such as angiogenesis and immune response. In cancer, it is associated with neoplastic progression, including invasion, migration, and metastasis. Furthermore, ALCAM is considered one of the cancer stem cell markers such as ALDH1 (ALDH1A1) and SALL4. The PD-L1 (CD274)/PD-1 (PDCD1, CD279) pathway is crucial for the modulation of immune responses in normal cells. Nevertheless, pathologic activation of the PD-L1/PD-1 pathway participates in immune evasion by tumor cells. Many PD-L1-expressing tumor cells have been identified in different types of cancer, including malignant mesothelioma. In this study, 175 well-characterized primary diffuse pleural mesotheliomas, including the epithelioid (n = 148), biphasic (n = 15), and sarcomatoid (n = 12) histotypes, were evaluated immunohistochemically for cancer stem cell markers (ALCAM, ALDH1, and SALL4) and PD-L1 expression. Twenty-five percent of the mesotheliomas (43/175) expressed ALCAM, whereas ALDH1 and SALL4 positivity was seen in 1% to 2% of cases. Thirty-three percent of the analyzed tumors (57/175) contained PD-L1-positive cells. Overall survival was significantly decreased in the cohort of patients with ALCAM- or PD-L1-positive tumors (both P < .01). Furthermore, the multivariate Cox hazards regression analysis identified ALCAM and PD-L1 (both P < 0.01) as potential independent risk factors. Thus, a combination of these 2 markers might be useful for prognostication and planning the treatment of patients with malignant pleural mesothelioma.

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Section: Introductionmentioning

confidence: 99%

Expression of ALCAM (CD166) and PD-L1 (CD274) independently predicts shorter survival in malignant pleural mesothelioma

et al. 2018

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“…Because MPM has a partial fibroblastic phenotype in the context of EMT, it has been postulated that this may, in part, explain the aggressiveness of this cancer by conferring both its high invasiveness and chemoresistance [ 13 ]; in particular, with regard to the epithelioid rather than sarcomatoid histotype of MPM [ 13 ]. In this regard, the epithelioid and sarcomatoid histologic variants of MPM can be considered as E- and M-parts of the EMT axis, with the biphasic histotype considered an intermediate [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…Because MPM has a partial fibroblastic phenotype in the context of EMT, it has been postulated that this may, in part, explain the aggressiveness of this cancer conferring both high invasiveness and chemoresistance [ 13 ], and in this regard, it may be applied to the epithelioid versus sarcomatoid histotype of MPM [ 13 ]. In this regard, the epithelioid and sarcomatoid histologic variants of MPM can be considered as E- and M-parts of the EMT axis, with the biphasic histotype considered an intermediate [ 14 ]. In support of this, hierarchical clustering of transcriptomic data from MPM separates this cancer into two distinct molecular subgroups, and one subgroup (C2) with an associated EMT molecular signature has worse overall survival (OS) [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

In Silico and In Vitro Analyses of LncRNAs as Potential Regulators in the Transition from the Epithelioid to Sarcomatoid Histotype of Malignant Pleural Mesothelioma (MPM)

Singh

Heery

Gray

2018

IJMS

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Malignant pleural mesothelioma (MPM) is a rare malignancy, with extremely poor survival rates. At present, treatment options are limited, with no second line chemotherapy for those who fail first line therapy. Extensive efforts are ongoing in a bid to characterise the underlying molecular mechanisms of mesothelioma. Recent research has determined that between 70–90% of our genome is transcribed. As only 2% of our genome is protein coding, the roles of the remaining proportion of non-coding RNA in biological processes has many applications, including roles in carcinogenesis and epithelial–mesenchymal transition (EMT), a process thought to play important roles in MPM pathogenesis. Non-coding RNAs can be separated loosely into two subtypes, short non-coding RNAs (<200 nucleotides) or long (>200 nucleotides). A significant body of evidence has emerged for the roles of short non-coding RNAs in MPM. Less is known about the roles of long non-coding RNAs (lncRNAs) in this disease setting. LncRNAs have been shown to play diverse roles in EMT, and it has been suggested that EMT may play a role in the aggressiveness of MPM histological subsets. In this report, using both in vitro analyses on mesothelioma patient material and in silico analyses of existing RNA datasets, we posit that various lncRNAs may play important roles in EMT within MPM, and we review the current literature regarding these lncRNAs with respect to both EMT and MPM.

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“…It is also expressed in 95.8 % of glioma tumor cells and is correlated with disease prognosis. The expression of the nestin has been noted to be associated with poor disease prognosis in malignant pleural mesothelioma [53]. Therefore, it is mainly expressed in the invasive tumor cells that are located at the peripheral side of tumor rather than tumor center [54].…”

Section: Heterogeneity Of Tumor Cells Before Treatmentmentioning

confidence: 99%

Mechanisms of tumor cell resistance to the current targeted-therapy agents

et al. 2016

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Resistance to chemotherapy agents is a major challenge infront of cancer patient treatment and researchers. It is known that several factors, such as multidrug resistance proteins and ATP-binding cassette families, are cell membrane transporters that can efflux several substrates such as chemotherapy agents from the cell cytoplasm. To reduce the adverse effects of chemotherapy agents, various targeted-based cancer therapy (TBCT) agents have been developed. TBCT has revolutionized cancer treatment, and several agents have shown more specific effects on tumor cells than chemotherapies. Small molecule inhibitors and monoclonal antibodies are specific agents that mostly target tumor cells but have low side effects on normal cells. Although these agents have been very useful for cancer treatment, however, the presence of natural and acquired resistance has blunted the advantages of targeted therapies. Therefore, development of new options might be necessary. A better understanding of tumor cell resistance mechanisms to current treatment agents may provide an appropriate platform for developing and improving new treatment modalities. Therefore, in this review, different mechanisms of tumor cell resistance to chemotherapy drugs and current targeted therapies have been described.

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Expression of the Stem Cell Factor Nestin in Malignant Pleural Mesothelioma Is Associated with Poor Prognosis

Cited by 10 publications

References 31 publications

Expression of ALCAM (CD166) and PD-L1 (CD274) independently predicts shorter survival in malignant pleural mesothelioma

Expression of ALCAM (CD166) and PD-L1 (CD274) independently predicts shorter survival in malignant pleural mesothelioma

In Silico and In Vitro Analyses of LncRNAs as Potential Regulators in the Transition from the Epithelioid to Sarcomatoid Histotype of Malignant Pleural Mesothelioma (MPM)

Mechanisms of tumor cell resistance to the current targeted-therapy agents

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