scholarly journals Correlation Between Baseline Osteoprotegerin Serum Levels and Prognosis of Advanced-Stage Colorectal Cancer Patients

2018 ◽  
Vol 45 (2) ◽  
pp. 605-613 ◽  
Author(s):  
Enrico De Toni ◽  
Dorothea Nagel ◽  
Alexander B. Philipp ◽  
Andreas Herbst ◽  
Isabel Thalhammer ◽  
...  

Background/Aims: Osteoprotegerin (OPG) is a soluble receptor of the pro-apoptotic cytokine TRAIL which is thought to contribute to tumour development by inhibiting apoptosis or affecting other aspects of tumour biology, including cell proliferation and immune response. Although immunohistochemical studies suggest that OPG correlates with survival in metastatic colorectal cancer (mCRC), only scarce data are available on serum OPG in CRC patients. Methods: In this pilot study, we assessed the prognostic significance of serum OPG and CEA (Carcinoembryonic antigen) in 81 patients with UICC (Union for International Cancer Control) stage-IV mCRC. OPG was additionally assessed by immunohistochemistry in primary tissue samples from 33 patients of the same cohort. Results: Baseline serum OPG correlated with CEA (r=0.36, p=0.0011), but independently predicted survival of mCRC patients. Life expectancy was poorer in patients with OPG levels above the median concentration of 51ng/ml (median overall survival [95% confidence interval] 1.8 years [1.3-3.0] vs. 1.0 [0.7-1.2] p=0.013). Patients with high levels of both OPG and CEA had an even poorer life expectancy vs. low-OPG/low-CEA patients (0.9 years [0.6-1.5] vs. 3 years [1.2-4.4], p=0.015), indicating that CEA and OPG have additive prognostic significance. Immunohistochemical analysis of OPG failed to show a correlation between OPG staining and survival (p=0.055) or OPG concentration from matched serum samples. Conclusions: This pilot study provides evidence of independent prognostic significance of serum OPG in patients with advanced mCRC and warrants its further prospective validation.

2017 ◽  
Vol 60 (10) ◽  
pp. 1041-1049 ◽  
Author(s):  
Keiichi Arakawa ◽  
Kazushige Kawai ◽  
Soichiro Ishihara ◽  
Keisuke Hata ◽  
Hiroaki Nozawa ◽  
...  

2020 ◽  
Vol 13 ◽  
pp. 175628482097119
Author(s):  
Hiroaki Nozawa ◽  
Shigenobu Emoto ◽  
Koji Murono ◽  
Yasutaka Shuno ◽  
Kazushige Kawai ◽  
...  

Background: Systemic therapy can cause loss of skeletal muscle mass in colorectal cancer (CRC) patients in the neoadjuvant and palliative settings. However, it is unknown how the body composition is changed by chemotherapy rendering unresectable CRC to resectable disease or how it affects the prognosis. This study aimed at elucidating the effects of systemic therapy on skeletal muscles and survival in stage IV CRC patients who underwent conversion therapy. Methods: We reviewed 98 stage IV CRC patients who received systemic therapy in our hospital. According to the treatment setting, patients were divided into the conversion, neoadjuvant chemotherapy (NAC), and palliation groups. The cross-sectional area of skeletal muscles at the third lumbar level and changes in the skeletal muscle index (SMI), defined as the area divided by height squared, during systemic therapy were compared among patient groups. The effects of these parameters on prognosis were analyzed in the conversion group. Results: The mean SMI increased by 9.4% during systemic therapy in the conversion group ( n = 38), whereas it decreased by 5.9% in the NAC group ( n = 18) and 3.7% in the palliation group ( n = 42, p < 0.0001). Moreover, patients with increased SMI during systemic therapy had a better overall survival (OS) than those whose SMI decreased in the conversion group ( p = 0.025). The increase in SMI was an independent predictor of favorable OS on multivariate analysis (hazard ratio 0.25). Conclusions: Stage IV CRC patients who underwent conversion to resection often had an increased SMI. On the other hand, a decrease in the SMI during systemic therapy was a negative prognostic factor in such patients.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10050-10050
Author(s):  
G. Nakayama

10050 Background: The incidence of colorectal cancer (CRC), one of the commonest malignancies worldwide, is still increasing. Despite advances in the diagnostic procedure, a large number of patients with CRC still presents with advanced disease. More sensitive and efficient diagnostic technique would make an impact on the prognosis of CRC patients through improving their compliance to the screening program, hence allowing earlier detection of the disease. To test the hypothesis that p16 methylation may serve as a marker for the diagnosis of CRC, we quantified the methylation levels of p16 in the serum DNA of CRC patients. Methods: Fresh specimens of 168 CRC and corresponding noncancerous tissues were obtained surgically at the Department of Surgery II, Nagoya University Graduate School of Medicine, together with the corresponding serum samples obtained 1 week prior to surgery. We defined the p16 methylation rate (p16 MR, in %) as follows: CM/(CM + CU) × 100%. CM is the concentration of methylated p16 sequences and CU is the concentration of unmethylated p16 sequences measured by quantitative methylation-specific PCR (Q-MSP) after bisulfite conversion. The relationship between the p16 MR and clinicopathologic findings were evaluated. Results: Aberrant p16 promoter methylation was found in 59% (99 of 168) of surgically resected CRC tissues. None of the corresponding normal tissues had methylated p16 sequences. 37% (37 of 99) serum samples of the CRC patients with tumoral p16 methylation had the same alterations. p16 MRs of 99 serum samples with tumoral p16 methylation were 0 to 68.9 (mean was 5.43±11.01). p16 MRs were significantly correlated with lymph node metastasis (P=0.001), lymphatic invasion (P=0.001) and venous invasion (P=0.020) of CRCs. p16 MRs increased significantly with tumor stage [stage I : 0.94 ± 1.68, stage II : 2.33 ± 5.19, stage III : 8.49 ± 14.22, stage IV : 10.03 ± 14.27 (P = 0.021)]. Moreover, the survival of patients with low p16 MR was significantly superior to those with high p16 MR (P=0.006). Conclusions: These results suggest that quantification of p16 methylation in the serum DNA might be a novel diagnostic tool and a prognostic factor for CRC. No significant financial relationships to disclose.


F1000Research ◽  
2014 ◽  
Vol 3 ◽  
pp. 180 ◽  
Author(s):  
Tianhua Guo ◽  
Marcin Krzystanek ◽  
Zoltan Szallasi ◽  
Arpad Szallasi

Thrombocytosis portends adverse prognostic significance in many types of cancers including ovarian and lung carcinoma. In this study, we determined the prevalence and prognostic significance of thrombocytosis (defined as platelet count in excess of 400 × 103/μl) in patients with colorectal cancer. We performed a retrospective analysis of 310 consecutive patients diagnosed at our Institution between 2004 and 2013. The patients (48.7% male and 51.3% female) had a mean age of 69.9 years (+/- 12.7 years) at diagnosis. Thrombocytosis was found in a total of 25 patients, with a higher incidence in those with stage III and IV disease (14.4% of patients). Although the mean platelet count increased with the depth of tumor invasion (pT), its values remained within normal limits in the whole patient cohort. No patient with stage I cancer (n=57) had elevated platelet count at diagnosis. By contrast, five of the 78 patients (6.4%) with stage II cancer showed thrombocytosis, and four of these patients showed early recurrence and/or metastatic disease, resulting in shortened survival (they died within one year after surgery). The incidence of thrombocytosis increased to 12.2% and 20.6%, respectively, in patients with stage III and IV disease. The overall survival rate of patients with thrombocytosis was lower than those without thrombocytosis in the stage II and III disease groups, but this difference disappeared in patients with stage IV cancer who did poorly regardless of their platelet count. We concluded that thrombocytosis at diagnosis indicates adverse clinical outcome in colorectal cancer patients with stage II or III disease. This observation is especially intriguing in stage II patients because the clinical management of these patients is controversial. If our data are confirmed in larger studies, stage II colon cancer patients with thrombocytosis may be considered for adjuvant chemotherapy.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9571-9571
Author(s):  
Krisztian Homicsko ◽  
Michel A. Cuendet ◽  
Agata Mlynska ◽  
Bianca Moura ◽  
Christine Horak ◽  
...  

9571 Background: Checkpoint inhibitors have revolutionized the treatment of stage IV melanoma patients. Selection of patients for PD-1 monotherapy or CTLA4/PD1 combination remains an important challenge. We set out to perform a discovery study of pretreatment serum protein biomarkers to identify predictors of progression free survival (PFS) for ipilimumab (IPI) or ipilimumab/nivolumab (IPI/NIVO). Methods: We performed an exploratory analysis of baseline serum samples from 135 treatment-naive patients with metastatic melanoma included in the randomized phase II clinical trial, CheckMate 069 (NCT01927419). We used the RayBiotech 440 human cytokine array and evaluated the relationship of serum protein levels with 44 clinical parameters. R, Prism 7.0 and TensorFlow were used for analyses. Results: We focused on correlation of serum protein markers with PFS as a predictor of long-term benefit. In the IPI arm (n = 46), high FGF4 correlated with worse PFS outcome (p = 0.0012). However, FGF4 levels alone were unable to select responsive vs. non-responsive patients. In contrast, a set of three markers consisting of FGF4 ( < 760pg/ml), CCL15 ( > 2.7 ng/ml), and TACE ( > 600pg/ml) separated non-progressing versus progressing patients. Moreover a small group of FGF4-high patients who were concomitantly TIM-3-low also had longer PFS (combined of both: p = 0.0004, HRlogrank: 0.07, 95% CI: 0.03279 to 0.1533). The same markers did not discriminate between IPI/NIVO patients (p = 0.467, HR: 15). In the IPI/NIVO arm, three different markers could select patients. Patients either with low CCL2 ( < 72 pg/ml) or alternatively with high CCL2 combined with high PDGF-AA ( > 8.2 ng/ml) and low GASP-1 ( < 1.3 ng/ml) had longer PFS (p < 0.0001, HR: 0.115, 95% CI: 0.03848 to 0.3408). Conversely, these markers did not predict benefit for IPI-monotherapy. Conclusions: In this study we identified protein signatures in baseline serum that correlate with PFS for therapies with IPI or IPI/NIVO. The markers were exclusive for IPI or IPI/NIVO but not for both. Additional research is warranted to substantiate these results and evaluate the possibility of incorporating into clinical practice.


Surgery Today ◽  
2014 ◽  
Vol 45 (3) ◽  
pp. 315-321 ◽  
Author(s):  
Masatsune Shibutani ◽  
Kiyoshi Maeda ◽  
Hisashi Nagahara ◽  
Eiji Noda ◽  
Hiroshi Ohtani ◽  
...  

1996 ◽  
Vol 32 (5) ◽  
pp. 802-806 ◽  
Author(s):  
G. Flamini ◽  
G. Curigliano ◽  
C. Ratto ◽  
A. Astone ◽  
G. Ferretti ◽  
...  

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