Feasibility of multiple immunoexpression assay for immune tumor micrornvironment (I-TME) on matched metastatic and primary renal cell carcinoma (RCC) for patient prognostication and predictiveness to immunotherapy (preliminary analyses of the Meet URO 18 study).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16545-e16545
Author(s):  
Matteo Brunelli ◽  
Sara Elena Rebuzzi ◽  
Valerio Gaetano Vellone ◽  
Marta Sbaraglia ◽  
Gabriele Gaggero ◽  
...  
Keyword(s):  
Nk Cells ◽  
Primary Tumor ◽  
Progression Free Survival ◽  
Tissue Expression ◽  
Tissue Level ◽  
Antibody Testing ◽  
Tissue Samples ◽  
Primary Tumors ◽  
Cd8 Cells ◽  
Primary Renal Cell Carcinoma

e16545 Background: The Meet-URO 18 study is ongoing to assess the prognostic role of I-TME in advanced RCC patients treated with ≥second line nivolumab divided into two cohorts according to clinical benefit [progression-free survival ≥ 12 and ≤ 3 months]. We primarily assessed the feasibility of multiple antibody testing related to I-TME on matched metastases and primary tumor. Methods: Immunohistochemical analyses were used for the TME assessment of T-lineage (CD3, CD4, CD8), FOXP-3, granulocytes (CD15), macrophage-lineage (CD68), natural killer (NK)-cells (CD56), tumor cells (TCs) (CD56), B-lineage (CD20) and phosphorylated mTOR (phmTOR). TCs were quantitatively assessed for CD15, CD56 and phmTOR positivity. For T-, B- and CD68 cells within TC nests, the number of immunoreactive cells were counted with a microscopic field of x200 (0.933 mm2). Results: Overall, 42 tumor tissue samples (primary tumors, metastases) were available and for 17 patients both metastatic and primary tumor tissues were assessable for matched analyses. Among these patients, 12 had clear cell, 1 papillary and 4 mucinous tubular and spindle cell histotype according to WHO 2016 classification. Intratumoral T/CD8 cells ranged from 32 to >400 spots (mean 240; >400 in 7 samples) and intratumoral T/CD4 cells from 4 to >400 spots (mean 168; >400 in 5 samples). Nine samples showed absence of phmTOR expression, while 8 ranged from 10% to 90% of positive TCs. We did not observe countable NK-cells, whereas CD56 was visible in 5 samples (mean 55% of positive TCs). Intratumoral CD68 cells ranged from 34 to >400 spots (mean 175, >400 in 3 patients). Agreement of CD15 method of reporting granulocytic presence was high, thus only CD15 neoplastic expression was reported and ranged from 12% to 55% (mean 30%) in 15 patients. TME multiple analysis resulted equally clustered in 8 patients (<20% variability of single immuno-test) whereas the remaining 9 patients showed significant differences as percentage of immuno-tissue expression in at least one of the 5 immuno-indicators (T/CD8-CD4, C15, CD68, CD56, phmTOR). The remaining 8 samples of patients without matched analyses were used to test the feasibility of multiple analyses; among all antibodies exclusion of the CD20 and FOXP-3 final evaluation was needed, due to technical standardization. According to the 5 immuno-indicators, double-triple positive or penta-positive TME indicators may be identified and graded. Conclusions: Providing multiple immunoexpression platforms on a single specimen may be used as routine workflow. Profiling I-TME, especially CD56, CD15 on TCs and CD68 cells and phmTOR, deserves investigation with extensive control groups. A validation cohort will be tested at tissue level and in correlation with peripheral blood markers.

Telomerase Expression Predicts Unfavorable Outcome in Osteosarcoma

2004 ◽  
Vol 22 (18) ◽  
pp. 3790-3797 ◽  
Author(s):  
Robert P. Sanders ◽  
Rachid Drissi ◽  
Catherine A. Billups ◽  
Najat C. Daw ◽  
Marcus B. Valentine ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Primary Tumor ◽  
Progression Free Survival ◽  
Outcome Analysis ◽  
Negative Group ◽  
Primary Tumors ◽  
Free Survival ◽  
Positive Group ◽  
Alternative Lengthening ◽  
Group 3

Purpose Osteosarcoma is distinct from most cancers in that the majority of osteosarcomas lack telomerase expression and use the alternative lengthening of telomeres (ALT) mechanism to maintain telomeres. Laboratory studies suggest that compared with ALT, telomerase expression is associated with increased tumor aggressiveness. We evaluated the clinical significance of telomerase expression in human osteosarcoma. Patients and Methods Fifty-six osteosarcomas from 51 patients treated at St Jude Children's Research Hospital between 1982 and 2003 were evaluated for telomerase enzyme activity, mRNA expression of the catalytic component of telomerase (TERT), and presence of the ALT pathway. Results Outcome analysis was based on TERT mRNA expression in the primary tumor samples from 44 patients. Fourteen primary tumors expressed TERT mRNA (32%; eight TERT only, six TERT and ALT) and 30 did not express TERT mRNA (68%; 29 ALT, one no ALT). Progression-free survival (PFS) was inferior in the TERT-positive group compared with the TERT-negative group (3-year estimates, 21.4% ± 9.5% v 63.7% ± 11.1%; P = .014). Likewise, overall survival was inferior in the TERT-positive group compared with the TERT-negative group (3-year estimates, 42.9% ± 12.2% v 70.0% ± 9.9%; P = .031). Among 31 patients with nonmetastatic disease at diagnosis, PFS was lower in the TERT-positive group compared with the TERT-negative group (3-year estimates, 33.3% ± 13.6% v 72.0% ± 11.5%; P = .092). Conclusion Telomerase expression in primary tumor samples is associated with decreased PFS and OS in patients with osteosarcoma. Additional studies are warranted to better define the clinical utility of this molecular marker.

Contrast enhanced CT (CE-CT) changes and nephrometry down-scoring of unresectable primary renal cell carcinoma (RCC) tumors in patients (Pts) treated with neoadjuvant sunitinib.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 299-299 ◽  
Author(s):  
M. Salem ◽  
S. N. Shah ◽  
L. S. Wood ◽  
P. Elson ◽  
A. Medsinge ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Objective Response ◽  
Sign Test ◽  
Rank Test ◽  
Primary Tumors ◽  
Venous Thrombus ◽  
Nephrometry Score ◽  
Primary Renal Cell Carcinoma ◽  
Contrast Enhanced Ct ◽  
The Impact

299 Background: The impact of neoadjuvant sunitinib on CE-CT parameters and nephrometry score of primary RCC tumors remains unknown. Methods: Retrospective review of baseline and prenephrectomy CE-CT from a prospective phase II trial of neoadjuvant sunitinib (50 mg sunitinib continuous dosing) in unresectable primary RCC tumors with or without metastatic disease. CE-CT parameters and R.E.N.A.L. nephrometry score for each lesion were determined in pts who underwent subsequent surgery. RECIST and MASS criteria were used to assess primary tumor radiographic response. CT changes were analyzed using the sign test and Wilcoxon signed rank test. Results: Twenty nine pts were enrolled, of which 13 pts (85%M; median age 63y) underwent post-sunitinib resection of 16 primary tumors (3 pts had multifocal RCC). Post-therapy, 88% of tumors had decreased long diameter (median 32% decrease, p<0.001 vs. baseline), 88% decreased attenuation (median 30 HU reduction, p=0.006) and 69% increased necrosis (p=0.001). 56% of tumors had a decrease in nephrometry score (median 1 point decrease; 10 to 9, p=004). At baseline, 81% of tumors were highly complex by nephrometry score; following therapy 46% of the highly complex tumors became moderately complex. At baseline 13 tumors abutted renal hilar vital structures, whereas following treatment 4 tumors demonstrated abutment. Adenopathy decreased (range, 23%-83%) in 4/4 patients with enlarged baseline lymph nodes, with complete resolution in 1 patient. RECIST objective response was seen in 38% and SD in 56% of primary tumors; 1 tumor had PD based on size despite > 95% necrosis. MASS criteria response was favorable 38%, intermediate 62%. Two of four pts had reduction in extent of venous thrombus (1 pt from level 0 to resolved and 1 pt from level IV to II). Conclusions: Neoadjuvant sunitinib resulted in decreased size/attenuation, increased necrosis of the primary tumor and reduction in lymphadenopathy and venous thrombus in pts who underwent subsequent surgery. Sunitinib reduced the RENAL nephrometry score and facilitated nephrectomy, notably due to impact on tumor proximity to vital structures in the renal hilum. [Table: see text]

Correlation of histopathologic regression with progression free survival (PFS) in patients (pts) with RAS wildtype metastatic colorectal cancer (mCRC) under fluorouracil/folinic acid, irinotecan, and oxaliplatin (FOLFOXIRI) plus panitumumab (pmab) or FOLFOXIRI alone: Subgroup analysis of VOLFI (AIO-KRK-0109).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15024-e15024
Author(s):  
Stefanie Noepel-Duennebacke ◽  
Hendrik Juette ◽  
Celine Lugnier ◽  
Michael Geissler ◽  
Uwe Marc Martens ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Tumor Cells ◽  
Subgroup Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Braf V600e ◽  
Histopathological Response ◽  
Tissue Samples ◽  
Primary Tumors ◽  
Secondary Resection

e15024 Background: We recently demonstrated improved objective response rate in untreated all-RAS wildtype mCRC with the addition of the anti-EGFR-antibody pmab to FOLFOXIRI. In this subgroup analysis we focused on histopathological response as a predictive marker for PFS. Additionally we analyzed chemotherapy induced steatosis hepatitis (CASH) in both treatment arms. Methods: Tissue samples from pts. achieving secondary resection of liver metastases in VOLFI were analyzed. We defined a cut-off for very good histopathological response at 20% of residual tumor cells in proportion to the total tumor area. For CASH sinusoidal obstructive syndrome, ballooning, steatosis, cholestasis, fibrosis and inflammation were determined. PFS was estimated using LIFETEST procedure. Results: Tissue of 14/19 resected pts. was evaluable (pmab-FOLFOXIRI/FOLFOXIRI: 11/3). All showed partial remission by RECIST. Median age was 56 yrs. (32–67), male/female: 7/7. All primary tumors were located in the left colon. Molecular analysis detected 1 BRAF (V600E) mutation and 1 MSI-H tumor. Median treatment duration until resection in this cohort: pmab-FOLFOXIRI 7 cycles (3-12)/FOLFOXIRI 9.5 cycles (7-11).7 pts. achieved very good histopathological response with vital tumor cells ≤20% (pmab-FOLFOXIRI/FOLFOXIRI 5/2) and 7 pts. showed vital tumor cells >20% (pmab-FOLFOXIRI/FOLFOXIRI 6/1). The cut-off correlated with an improved PFS in the group ≤20 vs >20% (median PFS 12.40; confidence interval (CI) 6.43-51.22 vs PFS 9.88; CI 6.17-15.26 months). The severity of CASH was not increased by the addition of pmab. Conclusions: In this preliminary analysis of VOLFI histopathological response seems to correlate with a better PFS after secondary resection of liver metastases. There was no relevant difference in CASH between pmab-FOLFOXIRI vs. FOLFOXIRI alone. The trial is registered with ClinicalTrials.gov, NCT01328171. Clinical trial information: AIO-KRK-0109.

scholarly journals TERT, BRAF, and NRAS in Primary Thyroid Cancer and Metastatic Disease

2017 ◽  
Vol 102 (6) ◽  
pp. 1898-1907 ◽  
Author(s):  
Miguel Melo ◽  
Adriana Gaspar da Rocha ◽  
Rui Batista ◽  
João Vinagre ◽  
Maria João Martins ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Primary Tumor ◽  
Low Frequency ◽  
Distant Metastases ◽  
Braf Mutations ◽  
Tissue Samples ◽  
Primary Tumors ◽  
Thyroid Carcinomas ◽  
Cancer Metastases ◽  
Node Metastases

Abstract Context Little is known about the frequency of key mutations in thyroid cancer metastases and its relationship with the primary tumor genotype. Objectives To evaluate the frequency of TERT promoter (TERTp), BRAF, and NRAS mutations in metastatic thyroid carcinomas, analyzing primary thyroid tumors, lymph node metastases (LNMs), and distant metastases. Design and Patients Mutation analysis was performed in 437 tissue samples from 204 patients, mainly with papillary thyroid carcinomas (PTCs; n = 180), including 196 LNMs and 56 distant metastases. All the distant metastases included corresponded to radioiodine-refractory metastatic tissue. Results We found the following mutation frequency in primary PTCs, LNMs, and distant metastases, respectively: TERTp: 12.9%, 10.5%, and 52.4%; BRAF: 44.6%, 41.7%, and 23.8%; and NRAS: 1.2%, 1.3%, and 14.3%. There was a significant concordance between the primary tumor genotype and the corresponding LNM for all the genes, in particular BRAF-mutated PTC. The overall concordance between primary tumors and respective distant metastases was low. In the group of patients with PTCs, we found a high frequency of TERTp mutations and a low frequency of BRAF mutations in distant metastases, in comparison with the paired primary tumors. When present in distant metastases, BRAF mutations frequently coexisted with TERTp mutations. Conclusions When the genotype of primary tumors is compared with the genotype of LNMs, the concordance is high for all the genes studied. On the other hand, distant metastases show an enrichment in TERTp mutations and a decrease in BRAF mutations. TERTp mutations may play a role in distant metastases.

scholarly journals DNA Methylation in INA, NHLH2, and THBS4 Is Associated with Metastatic Disease in Renal Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 39
Author(s):  
Olga Katzendorn ◽  
Inga Peters ◽  
Natalia Dubrowinskaja ◽  
Joana M. Moog ◽  
Christel Reese ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Metastatic Disease ◽  
Primary Tumor ◽  
Renal Cell ◽  
Progression Free Survival ◽  
Classification Model ◽  
Primary Tumors ◽  
Independent Information ◽  
Tumor Tissues ◽  
Bivariate Logistic Regression

The detection of DNA methylation in primary tumor tissues could be relevant for early stratification of aggressive renal cell carcinomas (RCCs) as a basis for future personalized adjuvant therapy. Methylated TCGA KIRC based candidate CpG loci in INA, NHLH2, and THBS4 that are possibly associated with RCC metastasis were evaluated by pyrosequencing in 154 paired normal adjacent and primary tumor tissues, as well as in 202 metastatic tissues. Statistical analysis was carried out by bivariate logistic regression for group comparisons, log rank survival analysis, and unsupervised and supervised analysis for the classification of tumors. Increased methylation of INA, NHLH2, and THBS4 loci were significantly associated with distant metastasis in primary tumors (p < 0.05), tissue-specific hypermethylation in metastatic (p = 7.88 × 10−8, 5.57 × 10−10, 2.06 × 10−7) and tumor tissues (p = 3.72 × 10−24, 3.17 × 10−13, 1.58 × 10−19), and shortened progression free survival in patients (p = 0.03). Combined use of CpG site-specific methylation permits the discrimination of tissues with metastatic disease and reveals a significant contribution of CpG sites in all genes to the statistical classification model. Thus, metastasis in RCC is significantly associated with methylation alterations in INA, NHLH2, and THBS4 loci, providing independent information for the potential early detection of aggressive renal cancers as a rationale for stratifying patients to adjuvant therapies.

scholarly journals Rigid tumors contain soft cancer cells

2021 ◽  
Author(s):  
Thomas Fuhs ◽  
Franziska Wetzel ◽  
Anatol Fritsch ◽  
Xinzhi Li ◽  
Roland Stange ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Primary Tumor ◽  
Single Cells ◽  
Tissue Level ◽  
Surrounding Tissue ◽  
Primary Tumors ◽  
Tumor Mass ◽  
Cell Clusters ◽  
Cell Shapes

Abstract Palpation, as already mentioned in the ancient Egyptian medical text Ebers Papyrus, utilizes that solid tumors are stiffer than the surrounding tissue. However, cancer cell lines tend to soften, which may intuitively foster invasion by enhancing the ability of cancer cells to squeeze through dense tissue. This paradox raises questions besides the oxymoron itself: Does softness emerge from adaptation to the external microenvironment? Or are soft cells already present inside a rigid primary tumor mass to support cancer cell unjamming? We investigate primary tumor explants from patients with breast and cervix carcinomas on multiple length scales from the tissue level down to single cells. We find that primary tumors are highly heterogeneous in their mechanical properties. From the tissue level this heterogeneity persists down to the scale of individual cells in cancer cell clusters, resulting in a broad distribution of cell rigidities with a higher fraction of softer, more squeezable cells. Plus, squeezed cell shapes correlate with cancer cell motility. Mechanical modelling based on patient data reveals that a tumor mass as a whole is able to maintain a rigid, solid behavior even when it contains a significant fraction of very soft cells. Cell softening induced cancer cell unjamming generates heterogeneous cancer cell clusters with a solid backbone of rigid cells surrounded by soft motile cells.

scholarly journals Genetic Determinants for Prediction of Outcome of Patients with Papillary Thyroid Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2048
Author(s):  
Antónia Afonso Póvoa ◽  
Elisabete Teixeira ◽  
Maria Rosa Bella-Cueto ◽  
Rui Batista ◽  
Ana Pestana ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Patient Outcomes ◽  
Genetic Alterations ◽  
Papillary Thyroid ◽  
Tissue Samples ◽  
Primary Tumors ◽  
Persistent Disease ◽  
Increased Risk ◽  
Structural Disease

Papillary thyroid carcinoma (PTC) usually presents an excellent prognosis, but some patients present with aggressive metastatic disease. BRAF, RAS, and TERT promoter (TERTp) genes are altered in PTC, and their impact on patient outcomes remains controversial. We aimed to determine the role of genetic alterations in PTC patient outcomes (recurrent/persistent disease, structural disease, and disease-specific mortality (DSM)). The series included 241 PTC patients submitted to surgery, between 2002–2015, in a single hospital. DNA was extracted from tissue samples of 287 lesions (primary tumors and metastases). Molecular alterations were detected by Sanger sequencing. Primary tumors presented 143 BRAF, 16 TERTp, and 13 RAS mutations. Isolated TERTpmut showed increased risk of structural disease (HR = 7.0, p < 0.001) and DSM (HR = 10.1, p = 0.001). Combined genotypes, BRAFwt/TERTpmut (HR = 6.8, p = 0.003), BRAFmut/TERTpmut (HR = 3.2, p = 0.056) and BRAFmut/TERTpwt (HR = 2.2, p = 0.023) showed increased risk of recurrent/persistent disease. Patients with tumors BRAFwt/TERTpmut (HR = 24.2, p < 0.001) and BRAFmut/TERTpmut (HR = 11.5, p = 0.002) showed increased risk of structural disease. DSM was significantly increased in patients with TERTpmut regardless of BRAF status (BRAFmut/TERTpmut, log-rank p < 0.001; BRAFwt/TERTpmut, log-rank p < 0.001). Our results indicate that molecular markers may have a role in predicting PTC patients’ outcome. BRAFmut/TERTpwt tumors were prone to associate with local aggressiveness (recurrent/persistent disease), whereas TERTpmut tumors were predisposed to recurrent structural disease and DSM.

scholarly journals Metastatic Esophageal Carcinoma Cells Exhibit Reduced Adhesion Strength and Enhanced Thermogenesis

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1213
Author(s):  
Zihe Huo ◽  
Mariana Sá Santos ◽  
Astrid Drenckhan ◽  
Stefan Holland-Cunz ◽  
Jakob R. Izbicki ◽  
...  
Keyword(s):  
Esophageal Carcinoma ◽  
Tumor Cells ◽  
Cell Lines ◽  
Adhesion Strength ◽  
Primary Tumor ◽  
Carcinoma Cell ◽  
Metastatic Potential ◽  
Primary Tumors ◽  
Metastatic Cell ◽  
Carcinoma Cell Lines

Despite continuous improvements in multimodal therapeutic strategies, esophageal carcinoma maintains a high mortality rate. Metastases are a major life-limiting component; however, very little is known about why some tumors have high metastatic potential and others not. In this study, we investigated thermogenic activity and adhesion strength of primary tumor cells and corresponding metastatic cell lines derived from two patients with metastatic adenocarcinoma of the esophagus. We hypothesized that the increased metastatic potential of the metastatic cell lines correlates with higher thermogenic activity and decreased adhesion strength. Our data show that patient-derived metastatic esophageal tumor cells have a higher thermogenic profile as well as a decreased adhesion strength compared to their corresponding primary tumor cells. Using two paired esophageal carcinoma cell lines of primary tumor and lymph nodes makes the data unique. Both higher specific thermogenesis profile and decreased adhesion strength are associated with a higher metastatic potential. They are in congruence with the clinical patient presentation. Understanding these functional, biophysical properties of patient derived esophageal carcinoma cell lines will enable us to gain further insight into the mechanisms of metastatic potential of primary tumors and metastases. Microcalorimetric evaluation will furthermore allow for rapid assessment of new treatment options for primary tumor and metastases aimed at decreasing the metastatic potential.

scholarly journals Discordance of KRAS Mutational Status between Primary Tumors and Liver Metastases in Colorectal Cancer: Impact on Long-Term Survival Following Radical Resection

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2148
Author(s):  
Francesco Ardito ◽  
Francesco Razionale ◽  
Lisa Salvatore ◽  
Tonia Cenci ◽  
Maria Vellone ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Primary Tumor ◽  
Kras Mutation ◽  
Colorectal Tumor ◽  
Term Survival ◽  
Primary Tumors ◽  
Mutation Status ◽  
Primary Colorectal Tumor ◽  
Kras Mutation Status

If KRAS mutation status of primary colorectal tumor is representative of corresponding colorectal liver metastases (CRLM) mutational pattern, is controversial. Several studies have reported different rates of KRAS discordance, ranging from 4 to 32%. Aim of this study is to assess the incidence of discordance and its impact on overall survival (OS) in a homogenous group of patients. KRAS mutation status was evaluated in 107 patients resected for both primary colorectal tumor and corresponding CRLM at the same institution, between 2007 and 2018. Discordance rate was 15.9%. Its incidence varied according to the time interval between the two mutation analyses (p = 0.025; Pearson correlation = 0.2) and it was significantly higher during the first 6 months from the time of primary tumor evaluation. On multivariable analysis, type of discordance (wild-type in primary tumor, mutation in CRLM) was the strongest predictor of poor OS (p < 0.001). At multivariable logistic regression analysis, the number of CRLM >3 was an independent risk factor for the risk of KRAS discordance associated with the worst prognosis (OR = 4.600; p = 0.047). Results of our study suggested that, in the era of precision medicine, possibility of KRAS discordance should be taken into account within multidisciplinary management of patients with metastatic colorectal cancer.

scholarly journals Downregulation and Prognostic Performance of MicroRNA 224 Expression in Prostate Cancer

2013 ◽  
Vol 59 (1) ◽  
pp. 261-269 ◽  
Author(s):  
Konstantinos Mavridis ◽  
Konstantinos Stravodimos ◽  
Andreas Scorilas
Keyword(s):  
Prostate Cancer ◽  
Cox Regression ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Prognostic Indicator ◽  
Disease Stage ◽  
Clinical Value ◽  
Prostate Tumors ◽  
Tissue Samples ◽  
Total Rna

INTRODUCTION The extensive use of prostate-specific antigen as a general prostate cancer biomarker has introduced the hazards of overdiagnosis and overtreatment. Recent studies have revealed the immense biomarker capacity of microRNAs (miRNAs) in prostate cancer. The aim of this study was to analyze the expression pattern of miR-224, a cancer-related miRNA, in prostate tumors and investigate its clinical utility. METHODS Total RNA was isolated from 139 prostate tissue samples. After the polyadenylation of total RNA by poly(A) polymerase, cDNA was synthesized with a suitable poly(T) adapter. miR-224 expression was assessed by quantitative real-time PCR and analyzed with the comparative quantification cycle method, Cq(2−ΔΔCq). We performed comprehensive biostatistical analyses to explore the clinical value of miR-224 in prostate cancer. RESULTS miR-224 expression was significantly downregulated in malignant samples compared with benign samples (P &lt; 0.001). Higher miR-224 expression levels were found in prostate tumors that were less aggressive (P = 0.017) and in an earlier disease stage (P = 0.018). Patients with prostate cancer who were positive for miR-224 had significantly enhanced progression-free survival intervals compared with miR-224–negative patients (P = 0.021). Univariate bootstrap Cox regression confirmed that miR-224 was associated with favorable prognosis (hazard ratio 0.314, P = 0.013); nonetheless, multivariate analysis, adjusted for conventional markers, did not identify miR-224 as an independent prognostic indicator. CONCLUSIONS miR-224 is aberrantly expressed in prostate cancer. Its assessment by cost-effective quantitative molecular methodologies could provide a useful biomarker for prostate cancer.

Sign in / Sign up

Export Citation Format

Share Document