Molecular detection of occult nodal metastases in esophageal adenocarcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4540-4540
Author(s):  
I. Altomare ◽  
A. Pennathur ◽  
L. Xi ◽  
W. E. Gooding ◽  
V. R. Litle ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Lymph Nodes ◽  
Esophageal Adenocarcinoma ◽  
Molecular Analysis ◽  
Expression Levels ◽  
Qrt Pcr ◽  
Positive Expression ◽  
Disease Free ◽  
Gene Expression Levels

4540 Introduction: Esophageal adenocarcinoma (EAC) is an aggressive malignancy whose incidence is on the rise. Approximately 40% of patients with N0 disease will recur after theoretically curative surgery, suggesting that in early stage disease, metastatic spread is often undetected by routine pathology. Molecular techniques may more accurately detect micrometastatic spread of EAC, but the correlation between molecular analysis of nodes and prognosis is unknown. Our lab has previously identified and validated 4 markers whose gene expression levels are able to distinguish benign nodes from nodes with metastatic EAC: CK19, CK20, CEA and TACSTD1. We used quantitative real-time RT-PCR to evaluate the expression of these 4 markers in lymph nodes from 68 N0 and 62 N1 EAC patients to see if molecular staging is predictive of a worse clinical outcome. Methods: RNA was isolated from 1456 lymph nodes obtained from 130 patients who underwent resection of EAC. QRT-PCR was used to analyze gene expression for each of the 4 markers. Relative expression of each marker was compared with expression in 53 benign esophageal lymph nodes previously analyzed. Results: Analysis of 778 lymph nodes from 68 pN0 patients identified 71 nodes (9%) from 30 patients (44%) which showed positive expression of at least one marker, indicating occult metastases (and molecular upstaging). Analysis of 678 lymph nodes from 62 pN1 patients revealed 141 nodes (21%) from 40 patients (65%) which had positive expression of at least one marker in nodes that were pathologically negative. In the pathologically positive nodes from N1 patients, there was an encouraging 88% concordance between pathological and molecular analysis. After a median follow-up of 2 years, 13 N0 patients had recurrence of their cancer. Gene expression levels of 3 of the 4 markers (CK20, CEA and TACSTD1) correlated with significantly worse disease-free and overall survival among these N0 patients, with p values <0.05. Conclusion: We have shown that QRT-PCR of 3 independent genetic markers is predictive of significantly worse disease-free and overall survival among node-negative EAC patients by identifying lymph nodes with occult metastatic disease. Further analysis will reveal if the N1 patients with molecularly positive lymph nodes had significantly worse outcomes as well. No significant financial relationships to disclose.

Multiplexed Digital Quantification of mRNA Abundance: a Highly Reproducible, PCR–independent Assessment of BAALC, ERG, and MN1 mRNA Levels in Acute Myeloid Leukemia (AML) Bone Marrow (BM) and Peripheral Blood (PB) Samples.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1599-1599
Author(s):  
Jacqueline E. Payton ◽  
Guido Marcucci ◽  
Michael D. Radmacher ◽  
Kati Maharry ◽  
Christian Langer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Correlation Coefficients ◽  
Mrna Abundance ◽  
White Blood Count ◽  
Spearman Correlation ◽  
Expression Levels ◽  
Rna Quality ◽  
Qrt Pcr ◽  
Digital Quantification ◽  
Gene Expression Levels

Abstract Abstract 1599 Poster Board I-625 The greatest obstacle to routine clinical testing of gene expression levels has been the lack of reproducibility of currently used methodologies, such as quantitative reverse transcriptase PCR (qRT-PCR) and microarray expression profiling. While these assays are useful for retrospective analyses of batched samples, they cannot be used for upfront evaluation of individual patients (pts) for molecular risk and treatment assignment. To overcome this barrier, we tested a recently developed, high throughput, PCR-independent, digital quantification technology, the nCounter system (Nanostring® Technologies). This system counts individual mRNA molecules, rather than measuring non-linear fluorescence generated by PCR-amplified targets (eg qRT-PCR). Using 72 AML samples and spike-in controls, we and collaborators demonstrated that the nCounter system is highly reproducible, sensitive, and accurate to femtomolar concentrations (Payton, J, et al. JCI 119:1714-26; Geiss, G, et al. Nat Biotech 26:317-25). Here we validated this technology using an independent set of 101 pts with a diagnosis of de novo cytogenetically normal AML. At diagnosis, pts presented with FAB subtypes M0, M1, M2, M4, M5(A, B), had a median age of 43 years (range 19-59), median white blood count of 28.5× 103/μL (range 1.4-273.0), median of 69% BM blasts (range 22-95) and median of 65% PB blasts (range 0-97). Paired BM and PB specimens were available for 27 pts; blast percentages were ≥ 20% for all paired specimens. We used the nCounter system to measure mRNA abundance (‘counts‘) of 27 genes whose expression correlates with clinical and/or pathological criteria, including 3 genes associated with prognosis (BAALC, ERG, MN1), and control/housekeeping genes (GAPDH, ABL, Actin). Briefly, mononuclear cells from pretreatment BM or PB were enriched on Ficoll-Hypaque gradients and RNA was isolated using Trizol reagent; 100ng of total RNA was assayed in triplicate by nCounter according to the manufacturer's protocols. The nCounter results demonstrated substantial reproducibility, with a median CV [coefficient of variation, (standard deviation/mean *100)] <6% across replicates. In addition, the nCounter counts for BAALC, ERG, and MN1 normalized to ABL were highly correlated with the ABL-normalized qRT-PCR results. Significant correlation was observed for all 3 genes, with the following Spearman correlation coefficients: BAALC r = 0.9, ERG r = 0.7, and MN1 r = 0.8 (all p<0.001). Correlation of BAALC, ERG, and MN1 nCounter counts with the expression levels measured by Affymetrix® HG-U133 plus 2.0 microarrays were also tested. Summary measures of microarray gene expression levels were computed using the Robust Multichip Average method, which incorporates quantile normalization of arrays. Significant correlation of nCounter and microarray results was observed, with Spearman correlation coefficients as follows: BAALC r = 0.96, ERG r = 0.8, and MN1 r = 0.8 (all p<0.001). For the 27 sets of paired samples, nCounter results for BM and PB were also significantly correlated, with Spearman correlation coefficients of BAALC r = 0.9, ERG r = 0.7, and MN1 r = 0.6 (all p<0.001). Because RNA quickly degrades if not promptly isolated from PB or BM, and degraded RNA often fails qRT-PCR assays, we determined whether RNA quality affected nCounter performance by assessment of standard quality parameters, including ratio of absorbance at 260 and 280 nm (260:280, a measure of RNA purity, acceptable 1.8-2.0) and RNA Quality Index (RQI, which assesses 18S:28S rRNA ratio and RNA degradation, 7-10 acceptable). Quality ranged from very high, with 260:280 ratios >1.9 and RQI scores >9, to relatively low, with 260:280 ratios <1.8, RQI scores <4, and degraded RNA visible on the Experion® RNA chip. Such a range of RNA quality is consistent with our experience with clinical specimens, which may be delayed in transit to the laboratory. Nevertheless, fewer than 3% of nCounter assays failed to generate acceptable results (11/393 assays), likely because no PCR step is required. Our results show that the nCounter system is a rapid, relatively inexpensive ($0.72/assay), and highly reproducible methodology that will be very useful for routine diagnostic testing of prognostic gene expression and upfront molecular-risk assessment for treatment guidance in AML pts. Disclosures No relevant conflicts of interest to declare.

Aberrant Expression of the MLL5, BAALC, ID1, and WT1 Genes Is Associated with Higher Induction Mortality and Poorer Overall Survival in Acute Promyelocytic Leukemia Patients Treated with ATRA and Anthracycline-Based Chemotherapy: An International Consortium On Acute Promyelocytic Leukemia Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1407-1407
Author(s):  
Antonio R Lucena-Araujo ◽  
Rafael Henriques Jacomo ◽  
Haesook T Kim ◽  
Raul A Melo ◽  
Rosane Bittencourt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Board Of Directors ◽  
Acute Promyelocytic Leukemia ◽  
Outcome Prediction ◽  
Promyelocytic Leukemia ◽  
Advisory Committees ◽  
Aberrant Expression ◽  
Expression Levels ◽  
Gene Expression Levels

Abstract Abstract 1407 Background: Aberrant expression of MLL5, BAALC, ID1, and WT1 genes is frequently associated with inferior outcome in cytogenetically normal acute myeloid leukemia patients (Damm et al. Blood 2011; 117(17):4561–8). The expression levels of these genes vary in patients with acute promyelocytic leukemia (APL), but the clinical significance of these findings remains unclear. Objective: (1) to determine if the gene expression levels of MLL5, BAALC, ID1, and WT1 are associated with clinical outcome of APL patients treated with ATRA and anthracycline-based chemotherapy, (2) to generate an integrative score (IS) based on these potential prognostic factors and clinical parameters and (3) to use this score for outcome prediction in APL. Design and Methods: One hundred and fifty APL patients (age, 15–73y) from seven different Brazilian institutions and treated according to the IC-APL protocol were included. The treatment schedule was identical to the PETHEMA-LPA 2005, except for the replacement of idarubicin by daunorubicin; ATRA treatment was initiated immediately in all cases in which the diagnosis of APL was suspected based on morphology. Gene expression profile was analyzed by Real-time PCR. Integer weights for the IS were derived from Cox proportional hazard model, using overall survival (OS) as outcome parameter. Hazard ratios (HR) for OS were calculated for each variable separately (Table 1). Variables with P<0.05 in univariate analyses were included in the model. Variables considered for the model inclusion consisted in 2 clinical (WBC counts, albumin levels) and 5 molecular markers (FLT3-ITD status and gene expression levels of MLL5, BAALC, ID1, and WT1). Other candidates, such as age, platelet count, gender, ECOG performance status, PML breakpoint and FAB subtype were not significant and not included in the score. The HR were converted to integer weights according to the following: variables with HR < 1 were excluded from analyses; variables with HR 3 1 and < 1.5 were assigned a weight of 1; variables with HR 3 1.5 and < 2.5 were assigned a weight of 2; variables with HR 3 2.5 were assigned a weight of 3. The final score was the sum of these integer weights. Based on maximally selected rank statistics, the scores were grouped into 3 risk-groups: 0–5 (low-IS), 6–9 (intermediate-IS), and > 9 (high-IS). Results: The integrative weights of variables analyzed are summarized in Table 1. The IS was modeled in 137 patients (median score: 6; range, 1–17). According to PETHEMA-GIMEMA relapse risk criteria, 22%, 23% and 70% of patients assigned in the low-IS (n=46), intermediate-IS (n=57) and high-IS (n=34) groups were deemed high-risk of relapse (P<0.001). Overall, 118 (86%) patients achieved CR; the remaining 19 patients (14%) experienced early death due to hemorrhage (n=12), therapy-related infection (n=6) and differentiation syndrome (n=1). Induction mortality was significantly higher in the high-IS group (low: 2%; intermediate: 15%; high: 26%) (P=0.001). CR was achieved in the low-, intermediate-, and high-IS group in 98%, 84%, and 73% of the patients, respectively (P=0.007). With a follow-up of 24 months among survivors, patients assigned in the high-IS group had a lower 2-y OS rate (63%) compared with those in the intermediate- (80%) and low-IS groups (97%; P<0.001). Eight relapses were recorded. The IS was not predictive of relapses (P=0.351). Conclusions: Our results suggest that MLL5, BAALC, ID1, and WT1 expression levels are associated with clinical outcome and that the IS may become a useful tool for outcome prediction in APL. Disclosures: Lo-Coco: Cephalon: Speakers Bureau; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees. Löwenberg:Skyline Diagnostics: Membership on an entity's Board of Directors or advisory committees.

scholarly journals HOXB9 Expression Correlates with Histological Grade and Prognosis in LSCC

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Chuanhui Sun ◽  
Changsong Han ◽  
Peng Wang ◽  
Yinji Jin ◽  
Yanan Sun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hox Genes ◽  
Histological Grade ◽  
Clinicopathological Features ◽  
Tissue Samples ◽  
Hox Gene ◽  
Expression Levels ◽  
Qrt Pcr ◽  
Upregulated Genes ◽  
Gene Expression Levels

The purpose of this study was to investigate the HOX gene expression profile in laryngeal squamous cell carcinoma (LSCC) and assess whether some genes are associated with the clinicopathological features and prognosis in LSCC patients. The HOX gene levels were tested by microarray and validated by qRT-PCR in paired cancerous and adjacent noncancerous LSCC tissue samples. The microarray testing data of 39 HOX genes revealed 15 HOX genes that were at least 2-fold upregulated and 2 that were downregulated. After qRT-PCR evaluation, the three most upregulated genes (HOXB9, HOXB13, and HOXD13) were selected for tissue microarray (TMA) analysis. The correlations between the HOXB9, HOXB13, and HOXD13 expression levels and both clinicopathological features and prognosis were analyzed. Three HOX gene expression levels were markedly increased in LSCC tissues compared with adjacent noncancerous tissues (P<0.001). HOXB9 was found to correlate with histological grade (P<0.01) and prognosis (P<0.01) in LSCC. In conclusion, this study revealed that HOXB9, HOXB13, and HOXD13 were upregulated and may play important roles in LSCC. Moreover, HOXB9 may serve as a novel marker of poor prognosis and a potential therapeutic target in LSCC patients.

scholarly journals Reference gene selection for qRT-PCR analyses of luffa (Luffa cylindrica) plants under abiotic stress conditions

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Min-dong Chen ◽  
Bin Wang ◽  
Yong-ping Li ◽  
Mei-juan Zeng ◽  
Jian-ting Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reference Gene ◽  
Reference Genes ◽  
Gene Selection ◽  
Expression Patterns ◽  
Suitable Reference Gene ◽  
Expression Levels ◽  
Qrt Pcr ◽  
Suitable Reference ◽  
Gene Expression Levels

AbstractSelecting suitable internal reference genes is an important prerequisite for the application of quantitative real-time PCR (qRT-PCR). However, no systematic studies have been conducted on reference genes in luffa. In this study, seven reference genes were selected, and their expression levels in luffa plants exposed to various simulated abiotic stresses [i.e., cold, drought, heat, salt, H2O2, and abscisic acid (ABA) treatments] were analyzed by qRT-PCR. The stability of the reference gene expression levels was validated using the geNorm, NormFinder, BestKeeper, and RefFinder algorithms. The results indicated that EF-1α was the most stably expressed and suitable reference gene overall and for the heat, cold, and ABA treatments. Additionally, UBQ expression was stable following the salt treatment, whereas TUB was identified as a suitable reference gene for H2O2 and drought treatments. The reliability of the selected reference genes was verified by analyzing the expression of copper/zinc superoxide dismutase (Cu/Zn-SOD) gene in luffa. When the most unstable reference genes were used for data normalizations, the resulting expression patterns had obvious biases when compared with the expression patterns for the most ideal reference genes used alone or combined. These results will be conducive to more accurate quantification of gene expression levels in luffa.

scholarly journals PD-1H Expression Associated With CD68 Macrophage Marker Confers an Immune-Activated Microenvironment and Favorable Overall Survival in Human Esophageal Squamous Cell Carcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Yuangui Chen ◽  
Rui Feng ◽  
Bailin He ◽  
Jun Wang ◽  
Na Xian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
T Cells ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Expression Levels ◽  
Tumor Tissues ◽  
Gene Expression Levels

Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal carcinoma (EC) in China. Although the PD-1 inhibitor pembrolizumab has been approved to treat patients with EC, its therapeutic efficacy is limited. Thus, additional immunotherapeutic targets for EC treatment are needed. Programmed Death-1 Homolog (PD-1H) is a negative checkpoint regulator that inhibits antitumor immune responses. Here, PD-1H expression in 114 patients with ESCC was evaluated by immunohistochemistry. Next, 12 randomly selected tumor tissue sections were used to assess the colocalization of PD-1H protein and multiple immune markers by multiplex immunohistochemistry. Our results demonstrated that PD-1H was expressed at high frequency in ESCC tumor tissues (85.1%). PD-1H protein was predominantly expressed in CD68+ tumor-associated macrophages and expressed at low levels in CD4+ T cells and CD8+ T cells in ESCC tumor tissues. Furthermore, based on ESCC data in The Cancer Genome Atlas (TCGA), the gene expression levels of PD-1H were positively associated with the infiltration levels of immune-activated cells especially CD8+ cytotoxic T cells. In contrast, the gene expression levels of PD-1H were negatively correlated with myeloid-derived suppressor cells (MDSCs). Importantly, PD-1H expression in tumor sites was significantly correlated with favorable overall survival in patients with ESCC. Collectively, our findings first provided direct information on the PD-1H expression pattern and distribution in ESCC, and positive correlation of PD-1H expression with overall survival suggested PD-1H expression levels could be a significant prognostic indicator for patients with ESCC. Future studies need to explore the immunoregulatory of PD-1H in the tumor microenvironment of ESCC.

XBP1 Expression Is An Important Prognostic Factor for Newly Diagnosed Myeloma Patients.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1686-1686
Author(s):  
Tina Bagratuni ◽  
Ping Wu ◽  
David Gonzalez de Castro ◽  
Emma L Davenport ◽  
Brian A Walker ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Plasma Cells ◽  
Critical Role ◽  
Clinical Samples ◽  
Newly Diagnosed ◽  
Expression Levels ◽  
Downstream Target ◽  
Lower Ratio ◽  
Gene Expression Levels

Abstract The immunoglobulin production of myeloma plasma cells means they are dependent on the unfolded protein response process (UPR), which controls protein production and ensures its proper translation and folding. Knockout mouse studies have highlighted the importance of IRE1, a transducer of the UPR signal and XBP1 its downstream target, in B cell development. Gene expression studies show that XBP1 is highly expressed in myeloma plasma cells and it is consistently deregulated in clinical samples. XBP1s, the active moiety, is a known myeloma survival factor and IgVH-XBP1s transgenic mice develop myeloma. In this work we demonstrate that XBP1s levels correlate with survival of myeloma patients and that targeting it with small molecules may be a useful therapeutic strategy. We have re-sequenced IRE1 and determined the gene expression levels of IRE1, total XBP1, XBP1 unspliced (XBP1u), and XBP1 spliced (XBP1s) in a large series of myeloma patients (n=260), and correlated biological findings with clinical characteristics and patient outcome. To quantitatively assess the expression of XBP1s and XBP1u variants, we have designed a novel real time PCR method (Lux Technology, Invitrogen) capable of determining the ratio of these transcripts within a sample. These results show that total IRE1 and XBP1 are highly expressed in all patients. In addition all patients expressed higher levels of XBP1s, the active transcription factor which is anti-apoptotic, compared to the inactive precursor XBP1u. We correlated XBP1s/u gene expression levels with clinical parameters in 159 newly diagnosed patients. This group of patients contained 68 females and 91 males with a median age of 64 years (range 39–89), B2M median = 7.45mg/mL (range 1.1–30mg/mL), haemoglobin median = 10.2g/dL (range 5.7–14.7g/dL) and ISS status stage 1 = 21%, stage 2 = 36%, and stage 3 = 36%. The XBP1s/u ratio demonstrated a statistically significant effect on overall survival (OS) in patients with high B2M (B2M &gt;5), with a cut-off ratio of 2.8 for the XBP1s/u expression (assigned using the quartile method). In this group of patients those with higher XBP1s/u have shorter survival (28 months) compared to those with lower XBP1s/u (not reached, 50+ months). (p = 0.033). The cause for the high and variable XBP1s levels is uncertain but could be mediated by IRE activity. Sequence analysis of the kinase and endoribonuclease domain of IRE1 identified 3/50 patients with an inactivating mutation in the endoribonuclease domain (G923V): patients with this mutation had a lower ratio of XBP1s to XBP1u and a longer survival. In conclusion, this study is the first to demonstrate the clinical significance of high XBP1s levels in myeloma and shows that patients with high levels of XBP1s have a shorter overall survival. Coupled with our previous study highlighting the critical role of the UPR in myeloma and the report of the XBP1s transgenic mouse model, the importance of the IRE1-XBP1 axis myeloma is now established, and its role as a therapeutic target needs to be explored.

Abstract 1660: Lack of correlation betweenin silicoprojection of function forCYP19A1andNFκB1SNPs and qRT-PCR-determined gene expression levels in colon tissue

2012 ◽  
Author(s):  
Rosalind B. Penney ◽  
Abbie Lundgreen ◽  
Aiwei Yao-Borengasser ◽  
Suzanne Williams ◽  
Ishwori B. Dhakal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Tissue ◽  
Expression Levels ◽  
Qrt Pcr ◽  
Gene Expression Levels

Molecular profiles of appendiceal adenocarcinoma: The UCSD experience.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 397-397
Author(s):  
John P. Shen ◽  
Devon Marcus McGee ◽  
Andrew M. Lowy ◽  
Paul Timothy Fanta
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Braf V600e ◽  
Appendiceal Cancer ◽  
Expression Levels ◽  
Appendix Cancer ◽  
Tumor Types ◽  
Gene Expression Levels

397 Background: Appendix cancer is rare, which precludes its study in randomized trials. As such, no evidence-based guidelines currently exist regarding the optimum systemic therapy for this disease entity. Typically, these patients are treated with regimens for colorectal carcinoma. Previous studies have shown high intra-tumoral mRNA levels of EGFR were significantly associated with response to irinotecan based chemotherapy, and that mucinous colorectal cancer overexpresses markers of resistance to 5-FU and oxaliplatin. We examined pharmacogenomics markers for appendiceal cancer and colon cancer to understand underlying similarities and differences between these tumor types. Methods: Intratumoral gene expression levels were assessed from paraffin-embedded tissue samples, using laser capture microdissection and quantitative real-time PCR from 69 colorectal and 34 appendiceal adenocarcinomas. A retrospective chart review was performed to correlate gene expression with overall survival. KRAS and BRAF mutational analyses and gene expression levels of ERCC1, TS, and EGFR were correlated with overall survival. Results: Appendiceal tumors had significantly higher expression of EGFR, (2.66 vs 1.4, p<.0001). No BRAF V600E mutations were found in the appendiceal tumors, incidence was 8.97% of the colon patients. UPDATE: In appendix cancer, KRAS mutations were noted in 65.5% of patients, there were no BRAF mutations. Median ERCC1, TS, EGFR, and VEGFR2A expression was 1.4, 1.21, 1.57, 2.19 respectively. Patients with metastatic appendiceal cancer had a significantly longer median OS than metastatic colon patients, (113 mo vs 43.9 mo, p = .0154). For appendiceal cancer patients, there was no significant correlation between any of the biomarkers and OS, although the sample size was underpowered for such an analysis. Conclusions: Metastatic appendiceal cancer patients have significantly better outcomes than metastatic colon cancer patients. Molecular analyses reveal significant differences between these tumor types. Further molecular study of appendiceal cancer is needed, as this study and others suggest fundamental differences in biology from colon cancer.

scholarly journals Differential Expression of MicroRNAs in Silent and Functioning Corticotroph Tumors

2020 ◽  
Vol 9 (6) ◽  
pp. 1838
Author(s):  
Araceli García-Martínez ◽  
Antonio C. Fuentes-Fayos ◽  
Carmen Fajardo ◽  
Cristina Lamas ◽  
Rosa Cámara ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Potential Role ◽  
Therapeutic Option ◽  
Pharmacological Treatments ◽  
Expression Levels ◽  
Qrt Pcr ◽  
Gene Expression Levels

The potential role of miRNAs in the silencing mechanisms of pituitary neuroendocrine tumors (PitNETs) has not been addressed. The aim of the present study was to evaluate the expression levels and the potential associated role of some miRNAs, pathways, and transcription factors in the silencing mechanisms of corticotroph tumors (CTs). Accordingly, the expression of miR-375, miR-383, miR-488, miR-200a and miR-103; of PKA, MAP3K8, MEK, MAPK3, NGFIB, NURR1, PITX1, and STAT3 were analyzed via qRT-PCR in 23 silent and 24 functioning CTs. miR-200a and miR-103 showed significantly higher expression in silent than in functioning CTs, even after eliminating the bias of tumor size, therefore enabling the differentiation between the two variants. Additionally, miR-383 correlated negatively with TBX19 in silent CTs, a transcription factor related with the processing of POMC that can participate in the silencing mechanisms of CTs. Finally, the gene expression levels of miR-488, miR-200a, and miR-103 were significantly higher in macroadenomas (functioning and silent) than in microadenomas. The evidence from this study indicates that miRNAs could be involved in the pathophysiology of CTs. The translational implications of these findings suggest that pharmacological treatments specifically targeting these miRNAs could become a promising therapeutic option for these patients.

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