Exploring the molecular biomarker utility of circCCT3 in multiple myeloma: A favorable prognostic indicator, particularly for R‐ISS II patients
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ABSTRACT:
SUBMITTER: Papatsirou M
PROVIDER: S-EPMC10878196 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:This study is to explore the prognostic significance of serum lipid profiles in patients with multiple myeloma (MM). The study retrospectively enrolled 307 MM patients in Zhongshan Hospital, Shanghai, China, from 2007 to 2016. We evaluated the prognostic significance of the pre-diagnostic serum lipid profile [cholesterol, triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (HDL), Apolipoprotein A1 (Apo A1) and Apolipoprotein B (Apo B)]. Prognostic factors identified through univariate and multivariate analysis were used to construct a new model based on Lasso Cox regression. Results indicated that lipid levels showed significant difference between ISS stages: Apo A1, Apo B, Cholesterol and LDL levels were lower in late ISS stage. However, only Apo A1 showed statistically significance in overall survival (OS), progression free survival (PFS) and cause specific survival (CSS) (P=0.038, P=0.028, P=0.011) in univariate Cox regression. Patients with higher Apo A1 displayed longer OS (median OS, 67 months vs. 30 months; P<0.001). Also, Apo A1 was revealed to be an independent prognostic indicator through multivariate analysis. Combining the Apo A1 level, Zhongshan Score model was constructed with Lasso regression for prognosis prediction. This model exhibited higher accuracy than International Staging System (ISS) and Durie and Salmon (DS) system. In conclusion, among all the serum lipid profiles, serum Apo A1 is a powerful prognostic indicator for patients with MM.
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Project description:Thymocyte selection-associated high mobility group box (TOX) genes represent a novel family of genes. Deregulated expression of TOXs has been reported in a variety of cancer types, including lung cancer. It has also been reported that TOXs are crucial regulators of the immune system. The present study systematically evaluated the prognostic values of TOX family members using a set of publicly accessible databases, including Oncomine, Kaplan-Meier plotter and cBioPortal. It was revealed that TOX expression profiles differed between lung cancer and normal tissues, and high expression of TOX mRNAs generally predicted improved survival outcomes. Notably, TOX3 expression was significantly increased in lung adenocarcinoma, compared with other pathological subtypes of lung cancer. Survival analysis demonstrated that elevated TOX3 expression was significantly associated with improved progression-free and overall survival in patients with lung adenocarcinoma. Furthermore, correlation analysis indicated that TOX3 expression was negatively correlated with the expression of programmed death-1 receptor (PD-1), PD-ligand 1 and Hepatitis A virus cellular receptor 2 in lung adenocarcinoma. These results indicated that TOX3 is a prognostic indicator and promising immunomodulatory factor in lung adenocarcinoma. Future studies investigating the role of TOX3 in lung cancer immunity are warranted.
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Project description:IntroductionTumor infiltrating lymphocytes may indicate an immune response to cancer development, but their significance remains controversial in breast cancer. We conducted this study to assess CD8+ (cytotoxic T) lymphocyte infiltration in a large cohort of invasive early stage breast cancers, and to evaluate its prognostic effect in different breast cancer intrinsic subtypes.MethodsImmunohistochemistry for CD8 staining was performed on tissue microarrays from 3992 breast cancer patients. CD8+ tumor infiltrating lymphocytes were counted as intratumoral when in direct contact with tumor cells, and as stromal in adjacent locations. Kaplan-Meier functions and Cox proportional hazards regression models were applied to examine the associations between tumor infiltrating lymphocytes and breast cancer specific survival.ResultsAmong 3403 cases for which immunohistochemical results were obtained, CD8+ tumor infiltrating lymphocytes were identified in an intratumoral pattern in 32% and stromal pattern in 61% of the cases. In the whole cohort, the presence of intratumoral tumor-infiltrating lymphocytes was significantly correlated with young age, high grade, estrogen receptor negativity, human epidermal growth factor receptor-2 positivity and core basal intrinsic subtype, and was associated with superior breast cancer specific survival. Multivariate analysis indicated that the favorable prognostic effect of CD8+ tumor infiltrating lymphocytes was significant only in the core basal intrinsic subgroup (Hazard ratio, HR = 0.35, 95% CI = 0.23-0.54). No association with improved survival was present in those triple negative breast cancers that lack expression of basal markers (HR = 0.99, 95% CI = 0.48-2.04) nor in the other intrinsic subtypes.ConclusionsCD8+ tumor infiltrating lymphocytes are an independent prognostic factor associated with better patient survival in basal-like breast cancer, but not in non-basal triple negative breast cancers nor in other intrinsic molecular subtypes.
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Project description:New approaches to stratify multiple myeloma patients based on prognosis and therapeutic decision-making, or prediction, are needed since patients are currently managed in a similar manner regardless of individual risk factors or disease characteristics. However, despite new and improved biomarkers for determining the prognosis of patients, there is currently insufficient information to utilise biomarkers to intensify, reduce or altogether change treatment, nor to target patient-specific biology in a so-called predictive manner. The ever-increasing number and complexity of drug classes to treat multiple myeloma have improved response rates and so clinically useful biomarkers will need to be relevant in the era of such novel therapies. Therefore, the field of multiple myeloma biomarker development is rapidly progressing, spurred on by new technologies and therapeutic approaches, and underpinned by a deeper understanding of tumour biology with individualised patient management the goal. In this review, we describe the main biomarker categories in multiple myeloma and relate these to diagnostic, prognostic and predictive applications.
| S-EPMC8461914 | biostudies-literature
Project description:Multiple myeloma (MM) is the second most common hematological malignancy, arising from terminally differentiated B cells, namely plasma cells. miRNAs are small non-coding RNAs that participate in the post-transcriptional regulation of gene expression. In this study, we investigated the role of nine miRNAs in MM. CD138+ plasma cells were selected from bone marrow aspirates from MM and smoldering MM (sMM) patients. Total RNA was extracted and in vitro polyadenylated. Next, first-strand cDNA synthesis was performed using an oligo-dT-adapter primer. For the relative quantification of the investigated miRNAs, an in-house real-time quantitative PCR (qPCR) assay was developed. A functional in silico analysis of the miRNAs was also performed. miR-16-5p and miR-155-5p expression was significantly lower in the CD138+ plasma cells of MM patients than in those of sMM patients. Furthermore, lower levels of miR-15a-5p, miR-16-5p, and miR-222-3p were observed in the CD138+ plasma cells of MM patients with osteolytic bone lesions, compared to those without. miR-125b-5p was also overexpressed in the CD138+ plasma cells of MM patients with bone disease that presented with skeletal-related events (SREs). Furthermore, lower levels of miR-223-3p were associated with significantly worse overall survival in MM patients. In conclusion, we propose a miRNA signature with putative clinical utility in MM.
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Project description:BackgroundThe recently proposed Huntington's Disease Integrated Staging System (HD-ISS) categorises individuals with the Huntintin genetic mutation into disease progression cohorts based on quantitative neuroimaging, cognitive, and functional markers for research purposes. Unfortunately, many research studies do not collect quantitative neuroimaging data, and so the authors of the HD-ISS have subsequently provided approximated cohort thresholds based on disease and clinical data alone. However, these are rough proxies that aim to maximise stage separation, and should not be considered as 1:1 substitutes for the HD-ISS. Notably, no wet biomarker met the stringent criteria required to be considered a landmark for HD-ISS categorisation. We have previously shown that levels of plasma neurofilament light (NfL), a neuronal marker associated with axonal injury, are associated with predicted years to clinical motor diagnosis (CMD). Our objective in the current study was to determine whether HD-ISS categorisation, particularly for stages prior to CMD, could be improved with consideration of plasma NfL levels.MethodsA total of 290 blood samples, and clinical measures, were collected from participants across all HD-ISS stages: n = 50 [Stage 0], n = 64 [Stage 1], n = 63 [Stage 2], n = 63 [Stage 3], as well as 50 healthy controls. Plasma NfL levels were measured using a Meso Scale Discovery assay.FindingsCohorts differed by age, cognitive function, CAG repeat length, and select UHDRS measures. Plasma NfL levels also differed significantly across cohorts. Approximately 50% of Stage 1 participants had plasma NfL levels indicative of predicted CMD within ten years.InterpretationOur findings suggest that plasma NfL levels may have use in enriching Stage 1 membership into sub-groups that are less than, and within, predicted 10 years until CMD.FundingThis work was supported by the National Institutes of Health (NS111655 to E.A.T.); the UCSD Huntington's Disease Society of America Center of Excellence; and the UCSD Shiley-Marcos Alzheimer's Disease Research Center (NIH-NIA P30 AG062429).
| S-EPMC10363447 | biostudies-literature
Project description:BackgroundAdrenomedullin (AM) is a multifunctional peptide which under basal conditions mainly regulates vasodilation and maintains vascular integrity but is also implicated in the pathogenesis of several malignancies, including multiple myeloma (MM). It has been shown that adrenomedullin is expressed by human myeloma cell lines and that it enhances MM-driven angiogenesis. However, the clinical impact of AM remains unknown.Materials and methodsOn that basis, we enrolled 32 newly diagnosed multiple myeloma patients (NDMM) and studied the potential of AM as a prognostic biomarker.ResultsWe report that elevated levels of AM trend with suboptimal treatment response and inferior survival of NDMM patients.
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Project description:PurposePrevious studies demonstrate that threonine and tyrosine kinase (TTK) is overexpressed in triple-negative breast cancer (TNBC), but there are conflicting results regarding its effect on TNBC survival. The purpose of this study was to assess the prognostic significance of TTK expression in primary TNBC.ResultsOf 169 consecutive cases eligible for this study, 164 included follow-up information. Cytoplasm and membrane TTK staining was observed in 99.4% of cases, while 5.9% displayed whole cell immunostaining. At a discriminating threshold of 55, elevated TTK expression was associated with prolonged disease free survival (DFS) (p < 0.001) and overall survival (OS) (p = 0.024) in primary TNBC and prolonged DFS in individual basal-like (p = 0.001) and non-basal-like (p = 0.001) TNBC subtypes. In addition, Cox regression analysis demonstrated that elevated TTK expression was an independent prognostic factor for DFS in TNBC (p < 0.001).MethodsTTK expression of 169 samples was tested by immunohistochemistry (IHC). A receiver operating characteristic (ROC) curve was used to identify a cutpoint for TTK expression, which was analyzed for its association with patients' clinicopathological factors and survival using Chi-square, log-rank, and Cox regression analyses.ConclusionsTTK is a favorable prognostic biomarker associated with TNBC survival.
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Project description:Multiple myeloma (MM) is a devastating cancer with a highly heterogeneous outcome. Because of the heterogeneity of myeloma cells, risk stratification is important for making therapeutic regimens. Nevertheless, no immunohistochemical predictive and prognostic marker has been constructed yet. In the present study, we explored the prognostic value of proteolipid protein 2 (PLP2) in MM patients using immunohistochemistry (IHC). We assessed PLP2 expression in bone marrow (BM) biopsy specimens obtained from 87 newly diagnosed MM (NDMM) patients. Correlations between PLP2 expression and clinicopathological features were analyzed. PLP2 expression was present in high-risk MM patients, which was increased with disease progression and poor prognosis. PLP2 was increasing in parallel with high beta-2 microglobulin (β2-MG) and lactate dehydrogenase (LDH). Furthermore, MM patients with low PLP2 expression could achieve a favorable treatment response. PLP2 may be a novel biomarker for prognostic prediction and a therapeutic target for anti-MM treatments.
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Project description:PurposeFor locally advanced rectal cancer, neoadjuvant concurrent chemoradiotherapy (CCRT) allows tumor downstaging and makes curative radical proctectomy possible. However, we lack a genetic biomarker to predict cancer prognosis or treatment response. We investigated the association between ubiquitin D (UBD) expression and clinical outcomes in rectal cancer patients receiving CCRT.Patients and methodsWe analyzed the genes associated with the protein modification process (GO:0036211) and identified the UBD gene as the most relevant among the top 7 differentially expressed genes associated with CCRT resistance. We collected tissue specimens from 172 rectal cancer patients who had received CCRT followed by a curative proctectomy. We examine the relationship between UBD expression and patient characteristics, pathological findings, and patient survival, such as metastasis-free survival (MeFS) and disease-specific survival.ResultsUpregulated UBD expression was associated with lower pre-CCRT tumor T stage (P = 0.009), lower post-CCRT tumor T stage (P < 0.001), lower post-CCRT nodal stage (P < 0.001), less vascular invasion (P = 0.015), and better tumor regression (P < 0.001). Using univariate analysis, we found that high UBD expression was correlated with better disease-free survival (DFS) (P < 0.0001), local recurrence-free survival (LRFS) (P < 0.0001) and MeFS (P < 0.0001). Moreover, multivariate analysis demonstrated that high UBD expression was associated with superior DFS (P < 0.001), LRFS (P = 0.01), and MeFS (P = 0.004).ConclusionUBD upregulation was linked to better clinical prognosis, favorable pathological features, and good treatment response in rectal cancer patients undergoing CCRT. These results suggest UBD is a biomarker for rectal cancer.
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