scholarly journals Mucin 16 and kallikrein 13 as potential prognostic factors in colon cancer: Results of an oncological 92-multiplex immunoassay

Tumor Biology ◽  
2019 ◽  
Vol 41 (7) ◽  
pp. 101042831986072
Author(s):  
Kajsa Björkman ◽  
Harri Mustonen ◽  
Tuomas Kaprio ◽  
Caj Haglund ◽  
Camilla Böckelman

Colon cancer represents one of the most common cancers in the world. Despite improved treatment, mortality remains high. In order to improve the assessment of prognosis for colon cancer patients, identifying new prognostic markers remains necessary. We analyzed preoperative serum samples from 148 colon cancer patients surgically treated at Helsinki University Hospital from 1998 through 2002 using a multiplex proximity extension assay (Oncology II panel, Olink Bioscience, Uppsala, Sweden), a panel constituting 92 immunological and oncological markers. We performed univariate and multivariate analyses on these patients and calculated the disease-specific survival among patients using the log-rank test for Kaplan–Meier estimates. In the univariate survival analysis of 92 biomarkers, 26 resulted in p < 0.1. Among these, eight biomarkers emerged as statistically significant (p < 0.05). Patients with low levels of kallikrein 13 had a poor prognosis. Moreover, patients with high levels of amphiregulin, carcinoembryonic antigen-related adhesion molecule 5, interleukin 6, mucin 16, syndecan 1, transforming growth factor alpha, and vimentin also had a poor prognosis. In the multivariate analysis, kallikrein 13 and mucin 16 emerged as independent prognostic markers. The role of kallikrein 13, a member of the serine protease kallikrein biomarker family, in tumorigenesis remains unclear. Mucin 16 is also known as carbohydrate antigen 125, a well-known ovarian cancer biomarker. Patients with low levels of kallikrein 13 (hazard ratio: 0.36; 95% confidence interval: 0.14–0.92; p = 0.033) and high levels of mucin 16 (hazard ratio: 3.15; 95% confidence interval: 1.68–5.93; p < 0.005) had a poor prognosis. Mucin 16 and kallikrein 13 represent independent prognostic markers for colon cancer. Furthermore, the clinical utility of mucin 16 and kallikrein 13 serum tests warrants additional investigation.

Oncotarget ◽  
2017 ◽  
Vol 8 (42) ◽  
pp. 72220-72226 ◽  
Author(s):  
Shushan Yan ◽  
Guangwang Dang ◽  
Xiaoyu Zhang ◽  
Chengwen Jin ◽  
Lang Qin ◽  
...  

2017 ◽  
Vol 7 (8) ◽  
pp. 723-731 ◽  
Author(s):  
Kaoru Ando ◽  
Hiroyasu Sukekawa ◽  
Aoi Takahata ◽  
Yusuke Kobari ◽  
Hayato Tsuchiya ◽  
...  

Background: Left ventricular dysfunction as part of takotsubo syndrome is reversible, and the long-term prognosis appears favorable. However, life-threatening complications are not uncommon during the acute phase, and it remains unclear whether renal dysfunction is a factor in complications suffered by hospitalized patients with takotsubo syndrome. The present study was conducted to investigate the implications of renal dysfunction in this setting. Methods: Data from 61 consecutive patients (male, 21; female, 40) diagnosed with takotsubo syndrome at our hospital between years 2010 and 2016 were evaluated retrospectively. In-hospital complications by definition were all-cause deaths and severe pump failure (Killip class ≥III). Results: Overall, 30 patients (49%) developed renal dysfunction. In the 32 patients (52%) who suffered in-hospital complications (mortality, 10; severe pump failure, 22), estimated glomerular filtration rate (eGFR) was significantly lower by comparison (51.3±29.8 vs. 69.5±29.0; p=0.019). Low eGFR (<30 ml/min per 1.73m2) proved independently predictive of in-hospital complications (hazard ratio =2.84, 95% confidence interval: 1.20–6.69) in multivariate Cox hazard analysis, also showing a significant association with peak event rate of Kaplan–Meier curve (log-rank test, p=0.0073). Similarly, patients with chronic kidney disease were at significantly greater risk of in-hospital complications (hazard ratio=2.49, 95% confidence interval: 1.01–5.98), relative to non-compromised counterparts (eGFR >60 ml/min per 1.73m2). Conclusion: Renal dysfunction is a simple but useful means of predicting complications in hospitalized patients with takotsubo syndrome, especially those with chronic kidney disease.


Neurosurgery ◽  
2015 ◽  
Vol 77 (6) ◽  
pp. 880-887 ◽  
Author(s):  
Eric J. Heyer ◽  
Joanna L. Mergeche ◽  
Shuang Wang ◽  
John G. Gaudet ◽  
E. Sander Connolly

BACKGROUND: Early cognitive dysfunction (eCD) is a subtle form of neurological injury observed in ∼25% of carotid endarterectomy (CEA) patients. Statin use is associated with a lower incidence of eCD in asymptomatic patients having CEA. OBJECTIVE: To determine whether eCD status is associated with worse long-term survival in patients taking and not taking statins. METHODS: This is a post hoc analysis of a prospective observational study of 585 CEA patients. Patients were evaluated with a battery of neuropsychometric tests before and after surgery. Survival was compared for patients with and without eCD stratifying by statin use. At enrollment, 366 patients were on statins and 219 were not. Survival was assessed by using Kaplan-Meier methods and multivariable Cox proportional hazards models. RESULTS: Age ≥75 years (P = .003), diabetes mellitus (P &lt; .001), cardiac disease (P = .02), and statin use (P = .014) are significantly associated with survival univariately (P &lt; .05) by use of the log-rank test. By Cox proportional hazards model, eCD status and survival adjusting for univariate factors within statin and nonstatin use groups suggested a significant effect by association of eCD on survival within patients not taking statin (hazard ratio, 1.61; 95% confidence interval, 1.09–2.40; P = .018), and no significant effect of eCD on survival within patients taking statin (hazard ratio, 0.98; 95% confidence interval, 0.59–1.66; P = .95). CONCLUSION: eCD is associated with shorter survival in patients not taking statins. This finding validates eCD as an important neurological outcome and suggests that eCD is a surrogate measure for overall health, comorbidity, and vulnerability to neurological insult.


2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Elena Orsenigo ◽  
Giulia Gasparini ◽  
Michele Carlucci

Many colorectal resections do not meet the minimum of 12 lymph nodes (LNs) recommended by the American Joint Committee on Cancer for accurate staging of colorectal cancer. The aim of this study was to investigate factors affecting the number of the adequate nodal yield in colorectal specimens subject to routine pathological assessment. We have retrospectively analysed the data of 2319 curatively resected colorectal cancer patients in San Raffaele Scientific Institute, Milan, between 1993 and 2017 (1259 colon cancer patients and 675 rectal cancer patients plus 385 rectal cancer patients who underwent neoadjuvant therapy). The factors influencing lymph node retrieval were subjected to uni- and multivariate analyses. Moreover, a survival analysis was carried out to verify the prognostic implications of nodal counts. The mean number of evaluated nodes was 24.08±11.4, 20.34±11.8, and 15.33±9.64 in surgically treated right-sided colon cancer, left-sided colon cancer, and rectal tumors, respectively. More than 12 lymph nodes were reported in surgical specimens in 1094 (86.9%) cases in the colon cohort and in 425 (63%) cases in the rectal cohort, and patients who underwent neoadjuvant chemoradiation were analysed separately. On univariate analysis of the colon cancer group, higher LNs counts were associated with female sex, right colon cancer, emergency surgery, pT3-T4 diseases, higher tumor size, and resected specimen length. On multivariate analysis right colon tumors, larger mean size of tumor, length of specimen, pT3-T4 disease, and female sex were found to significantly affect lymph node retrieval. Colon cancer patients with 12 or more lymph nodes removed had a significantly better long-term survival than those with 11 or fewer nodes (P=0.002, log-rank test). Rectal cancer patients with 12 or more lymph nodes removed approached but did not reach a statistically different survival (P=0.055, log-rank test). Multiple tumor and patients’ factors are associated with lymph node yield, but only the removal of at least 12 lymph nodes will reliably determine lymph node status.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S409-S410
Author(s):  
T Fujii ◽  
S Hibiya ◽  
C Maeyashiki ◽  
E Saito ◽  
K Takenaka ◽  
...  

Abstract Background 5-Aminosalicylates (5-ASA) are the key drugs in induction and maintenance therapy in ulcerative colitis (UC). Some UC patients are involved in 5-ASA intolerance after induction of oral 5-ASA compounds. There is no evidence of the prognosis including the risk of colectomy in 5-ASA intolerant UC patients. Methods The aim of this study is to establish the prognosis of 5-ASA intolerant UC patients in a multicenter cohort study. A retrospective review of a prospective multicenter database (2014–2018) of 1,574 UC patients was carried out and a total of 1,286 patients treated with oral 5-ASA compounds were enrolled. We compared the risk of colectomy and biologics induction between patients (i) tolerant to first 5-ASA compound (1079), (ii) intolerant to first 5-ASA compound but tolerant to other 5-ASA compound (107) and (iii) intolerant to 5-ASA compound and withdrawal of 5-ASA (100). Results We identified 1,286 patients with UC, of which 40 patients (3.1%) resulted in colectomy and 247 patients (19%) treated with biologics. Colectomy rate in patients (iii) intolerant to 5-ASA and withdrawal of 5-ASA were higher than (i) tolerant to first 5-ASA and (ii) intolerant to first 5-ASA but tolerant to other 5-ASA (9.0%, 2.7%, 1.9%, respectively). (iii) Patients withdrawal of 5-ASA showed higher risk of colectomy compared with (i) tolerant to first 5-ASA (Hazard ratio (HR) 4.71, 95% Confidence interval (CI): 2.04–10.8). The risk of colectomy among (ii) patients intolerant to first 5-ASA but tolerant to other 5-ASA showed no significant difference compared with (i) tolerant to first 5-ASA (HR 0.76, 95% CI: 0.43–1.35). The biologics induction rate in (iii) patients withdrawal of 5-ASA was significantly higher than (i) tolerant to first 5-ASA and (ii) intolerant to first 5-ASA but tolerant to other 5-ASA (37%, 18%, 16%, respectively). Also (iii) patients withdrawal of 5-ASA showed higher risk of induction with biologics compared with (i) tolerant to first 5-ASA (HR 2.35, 95% CI: 1.50–3.68). Those risk among (ii) patients intolerant to first 5-ASA but tolerant to other 5-ASA showed no significant difference compared with (i) tolerant to first 5-ASA (HR 0.76, 95% CI: 0.43–1.35). Conclusion Patients with UC who had 5-ASA intolerance and withdrew from 5-ASA showed poor prognosis. We should consider trying other 5-ASA compounds even if the patients had intolerance to one 5-ASA compound.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
D Sueta ◽  
T Nishihara ◽  
E Yamamoto ◽  
K Tsujita

Abstract Background The H2FPEF score is recognized as a simple method to diagnose heart failure (HF) with preserved left ventricular ejection fraction (HFpEF). Purpose We investigated the value of the H2FPEF score in predicting subsequent cardiovascular events in HFpEF patients. Methods This study was a retrospective, single-center, observational study. We calculated the H2FPEF scores for 404 consecutive HFpEF patients. Subjects were subdivided into low- (0–3), intermediate- (4–6), and high-score (7–9) groups and followed for 50-months. The primary and secondary endpoints were composite cardiovascular/ cerebrovascular events (cardiovascular death, non-fatal myocardial infarction, unstable angina pectoris, hospitalization for HF decompensation and non-fatal stroke) occurrence and HF-related events (hospitalization for HF decompensation) occurrence at 50-months, respectively. Results Kaplan–Meier analyses demonstrated a significantly higher incidence of cardiovascular/cerebrovascular events in proportion to a higher H2FPEF score (log-rank test, P=0.005). The HF-related event rate was higher in proportion to the H2FPEF score (log-rank test, P<0.001). Multivariate Cox hazard analyses identified the H2FPEF score (per 1 point) as an independent predictor of cardiovascular and HF-related events (Table, hazard ratio, 1.179; 95% confidence interval, 1.066–1.305; P=0.001 and hazard ratio, 1.288; 95% confidence interval, 1.134–1.463; P=0.001, respectively). Receiver operating characteristic analysis showed that the H2FPEF significantly predicted cardiovascular events (Figure A, AUC 0.626, 95% CI 0.557–0.693; P<0.001) and HF-related events (Figure B, AUC 0.680, 95% CI 0.600–0.759; P<0.001). The cutoff H2FPEF score was 5.5 for the identification of cardiovascular and HF-related events. Conclusion The H2FPEF score is a potentially useful marker for the prediction of cardiovascular and HF-related events in HFpEF patients.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4029-4029
Author(s):  
I. Sobhani ◽  
F. Roudot-Thoraval ◽  
F. Mesli ◽  
B. Landi ◽  
T. Aparicio ◽  
...  

4029 Background: Metastatic colon cancer patients may undergo chemotherapy without colon surgery. However, the outcome of patients has not been evaluated and antiagiogenic agents can not be given. The aim of the present cohort study was to analyse factors influencing patients’ survival. Methods: Consecutive patients [N=228, mean age (sd) 64 (12) yrs, median follow-up 20 mths;84 females] treated in 6 teaching hospitals received chemotherapy for metastatic colonic cancer, either as the first step, or after surgery. Progressive free survival (PFS) was estimated using Kaplan-Meïer method. Factors associated with PFS were tested by means of Log rank test and results are presented in terms of medians of survival (95% CI). Factors independently related to PFS were tested using a Cox model and results are presented as hazard ratio. Results: 105 patients with colon cancer and synchronous metastatsis underwent colon surgery prior to chemotherapy (68 males, mean age 64 yrs) when 123 patients were treated first by chemotherapy ± biotherapy (76 males, mean age 63 yrs). By univariate analysis, following factors were significantly associated with PFS: surgery first 25.5 (18.6 - 32.5) vs chemotherapy first 18.3 (14.7 - 21.9) mths p = 0.006; curative surgery: yes 35.7 (29.6 - 41.8) vs no 18.4 (15.6 - 21.2) mths p < 0.001; tumour histological differentiation : no : 13.4 (6.2 - 20.6) vs well : 24.7 (20.4 - 29.1) mths p<0.001; synchronous metastases: liver only 25.5 (20.5 - 30.6) vs peritonea&nodes : 18.4 (10.6 - 26.1) vs pulmonary & other sites : 16.5 (14.7 - 18.3) mths p < 0.0001; need for colonic stent: yes 16.4 (9.3 - 23.5) vs no 23.9 (21.1 - 26.7) months p < 0.0001; antiangiogenic drug: yes 36.6 (28.7 - 44.5) vs no : 20.7 (18.3 - 23.1) p = 0.033. After Cox multivariate analysis five independent factors were found to be associated with PFS. Conclusions: Colon surgery before chemotherapy plus bevacizumab appears to be the more appropriate choice, and associated with longer PFS, especially for those patients with well differentiated tumours and synchronous liver metastases. [Table: see text] No significant financial relationships to disclose.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 647-647
Author(s):  
Yuji Toiyama ◽  
Hiroyuki Fujikawa ◽  
Yasuhiro Inoue ◽  
Hiroki Imaoka ◽  
Masato Okigami ◽  
...  

647 Background: Albumin to globulin ratio (AGR) has been reported to predict long term mortality in patients with several cancers. However, prognostic impact of preoperative AGR in colon cancer patients with curative intent has not yet been fully addressed. Therefore, we, for the first time, investigated the association between AGR and clinico-pathological findings including overall survival (OS) and disease free survival (DFS) in stage I-III colon cancer patients. Methods: Clinicopathological findings including preoperative laboratory data (carcinoembryonic antigen [CEA] and AGR) from 251 curative colon cancer patients were assessed as indicators of early recurrence and poor prognosis in this retrospective study. AGR was calculated as [AGR = albumin/ (total protein - albumin)]. The cut-off value of AGR was 1.32 in current study. Results: Several clinicopathological categories related with tumor progression such as lymph node metastasis, T4 tumor, large tumor size, undifferentiated tumor, venous and lymphatic invasion, and high CEA were significantly associated with low AGR level. The patients with low AGR were significantly poorer OS (P = 0.001) and DFS (P = 0.003) than those with high AGR, respectively. In addition, multivariate analyses demonstrated that low AGR was independently associated with early recurrence (HR = 2.87, P = 0.007) and poor prognosis (HR = 2.56, P = 0.008), respectively. On the other hand, sub analysis of survival curves revealed that stage III colon cancer patients with low AGR were significantly poorer OS (P = 0.007) and DFS (P = 0.02) than those with high AGR, respectively. Furthermore, significantly poorer OS and DFS were also shown in stage I-II colon cancer patients with low AGR, respectively (OS: P = 0.02, DFS: P = 0.01). Conclusions: Preoperative AGR was an independent predictor of early recurrence and poor prognosis in curative colon cancer patients. AGR may represent a simple, potentially useful predictive biomarker for selecting stage I-II colon cancer patients who might need adjuvant chemotherapy. Furthermore, AGR may select candidates who are better to introduce more intensive adjuvant chemotherapy after curative operation in stage III colon cancer patients.


2011 ◽  
Vol 34 (6) ◽  
pp. 523-531 ◽  
Author(s):  
Arantza Fariña Sarasqueta ◽  
Eliane C. M. Zeestraten ◽  
Tom van Wezel ◽  
Gesina van Lijnschoten ◽  
Ronald van Eijk ◽  
...  

Blood ◽  
2010 ◽  
Vol 115 (19) ◽  
pp. 3960-3965 ◽  
Author(s):  
Martin Stern ◽  
Gerhard Opelz ◽  
Bernd Döhler ◽  
Christoph Hess

Abstract Posttransplantation non-Hodgkin lymphoma is a life-threatening complication after transplantation. Although pharmacologically suppressed adaptive immunity plays a major role in its development, the role of innate immunity in posttransplantation lymphoma is unknown. We assessed the 158 V/F polymorphism in the Fc-γ receptor 3A gene (FCGR3A), killer cell immunoglobulin-like receptor (KIR) genotype, KIR ligand status, and a single nucleotide polymorphism affecting the production of interferon-γ (IFN-γ; +874 A/T) in 236 patients with posttransplantation lymphoma reported to the Collaborative Transplant Study. In addition, polymorphisms in the interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) genes previously associated with lymphoma development were also typed. Using a split-cohort approach, gene/allele frequency was related to the 5-year patient survival after the diagnosis of lymphoma and compared with 100 control solid organ transplant recipients. FCGR3A and KIR genotype significantly influenced survival after diagnosis of posttransplantation lymphoma: the hazard of dying was reduced in homozygous carriers of the high-affinity V allele (hazard ratio 0.49, 95% confidence interval 0.29-0.82, P = .006), whereas carrying a genotype including KIR2DL2/KIR2DS2 increased the risk of dying (hazard ratio 1.49, 95% confidence interval 1.07-2.05, P = .02). KIR ligands and cytokine polymorphisms had no effect on survival. None of the genetic loci analyzed emerged as risk factors for lymphoma development.


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