1401

CRP

C-reactive protein, pentraxin-related;CRP;C-reactive protein, pentraxin-related

C-reactive protein|pentraxin 1

1q23.2

protein-coding

BACKGROUND: Breast cancer is a disease that continues to plague females during their entire lifetime. IL-6 and CRP are found to be elevated in various inflammatory and malignant diseases and their levels are found to correlate with the extent of the disease. The primary objective of this study was to determine the preoperative serum levels of IL-6 and CRP in breast carcinoma, and to correlate them with the staging of the disease and the prognosis. METHODS: 59 female patients admitted for breast cancer were identified for the study and were subjected to thorough evaluation. Serum levels of IL-6 were assessed via Enzyme-Linked Immuno-Sorbent Assay (ELISA), and CRP was measured via immunoturbidimetry. Histological findings included tumour size, lymph node (LN) metastasis, and tumour staging. Relevant investigations were made to find out the presence of distant metastasis. Statistical analysis of the data was then processed. RESULTS: Increases in cancer invasion and staging are generally associated with increases in preoperative serum IL-6 levels. IL-6 and CRP levels correlated with LN metastasis (P < 0.001, P < 0.001) and TNM stage (P < 0.001, P < 0.001). tumour invasion and the presence of distant metastasis is associated with higher IL-6 levels (P = 0.001, P = 0.009). When we established the cutoff value for IL-6 level (20.55 pg/dl) by ROC curve, we noted a significant difference in overall survival (OS; P = 0.008). However, CRP evidenced no significance with regard to patient's OS levels. Serum IL-6 levels were correlated positively with CRP levels (r(2) = 0.579, P < 0.01) CONCLUSION: Serum levels of IL-6 correlates well with the extent of tumor invasion, LN metastasis, distant metastasis and TNM staging thus enveloping all aspects of breast cancer.

Lymph node status is a key indicator of the best approach to treatment of invasive breast cancer. However, the accuracy with which lymph node metastasis is diagnosed is not currently satisfactory. New and more reliable methods that enable one to know who has a greater potential for lymph node metastasis would be highly desirable. We previously reported that lymph node involvement in esophageal and lung cancer may have a genetic component: C-reactive protein (CRP) 1846C>T genetic polymorphism. Here we examined the diagnostic value of CRP 1846C>T polymorphism for assessing the risk of lymph node metastasis in cases of invasive breast cancer. The study participants were 185 women with invasive breast cancer who underwent curative surgery with lymph node dissection. Using DNA from blood samples and polymerase chain reaction-restriction fragment length polymorphism, the utility of CRP genetic 1846C>T polymorphism (rs1205) for assessing the risk of lymph node metastasis was evaluated. Fifty-two (28 %) patients had lymph node metastasis. After the patients were divided into two groups based on their CRP 1846 genotypes (C/C+C/T and T/T), the clinical characteristics did not differ between the groups, but there was a significantly greater incidence of lymph node metastasis among patients in the T/T group. Moreover, the odds ratio for lymph node involvement in patients carrying the 1846 T/T genotype was more than 2.2 in multivariate logistic regression models. CRP genetic polymorphism may be a novel predictor of the risk of lymph node metastasis in invasive breast cancer.

BACKGROUND: The liver is the most common target organ in the metastasis of colorectal cancer (CRC). Synchronous liver metastases may confer a poorer prognosis than metachronous metastases, and genetic alterations and an inflammatory response have also been associated with a poor prognosis in cases of a liver metastasis arising from CRC. However, few studies have examined the relationship between KRAS mutations and inflammatory status in CRC, especially with respect to liver metastases. METHODS: The effect of the activated mitogen-activated protein kinase pathway and another protein involved in inflammation, C-reactive protein, in liver metastases were examined. We aimed to determine the impact of the CRP-specific single nucleotide polymorphism (SNP) rs7553007 in liver metastasis on the CRC-specific survival (CSS) of patients after colorectal liver metastasectomy. RESULTS: We found no significant differences in genotype distributions and allele frequencies at the CRP SNP rs7553007 between CRC patients with liver metastasis and the control group. CSS rates were low in the subgroup of patients with synchronous metastasis with the A-allele (A/A and A/G) at rs7553007 or mutated KRAS/BRAF in liver metastatic specimens. Furthermore, the CRP SNP rs7553007 (hazard ratio [HR] = 1.101; 95% confidence interval [CI] = 1.011-1.200; P = 0.027) and KRAS/BRAF mutations (HR = 2.377; 95%

BACKGROUND: Lymph node involvement is the most important prognostic factor in thoracic esophageal cancer. A more accurate molecular technique for diagnosing lymph node metastasis and a better understanding of the molecular mechanisms governing lymph node metastasis would be highly desirable. The purpose of this study is to examine the association between inflammation-related genetic polymorphisms and lymph node metastasis. METHODS: The study participants were 113 Japanese patients undergoing curative surgery for thoracic esophageal squamous cell cancer. DNA was extracted from blood samples and genetic polymorphisms in C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha and -beta, interferon (IFN)-gamma, transforming growth factor (TGF)- beta, interleukin (IL)-1beta, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-6 receptor, IL-10, and IL-12beta were investigated using the polymerase chain reaction-restriction fragment length polymorphism method. We then assessed the association between inflammation-related genes and lymph node metastasis. RESULTS: For CRP 1846C>T polymorphism, the frequency of the 1846T/T genotype was significantly higher in patients with lymph node metastasis (P = 0.0043), and the odds ratio (3.040) derived from logistic regression models indicated that the 1846T/T genotype significantly increases the likelihood of lymph node metastasis. In submucosal cancer, the utility of CRP 1846C>T polymorphism for predicting lymph node involvement was superior to usual methods (computed tomography and ultrasonography), with positive and negative predictive values of 69% and 75%, respectively. CONCLUSIONS: These findings suggest that CRP polymorphism is a potentially effective predictor of lymph node metastasis and may thus be useful for deciding on treatment strategy.

BACKGROUND: More than 40 % of patients with submucosal esophageal squamous cell carcinoma (ESCC) have lymph node metastasis. Furthermore, the potential presence of undetectable metastasis before treatment prompts surgeons to be aggressive with respect to lymph node dissection. Extending the indication for endoscopic resection, a minimally invasive treatment, to superficial ESCCs will require more accurate and individualized evaluation of lymph node metastasis. METHODS: The study participants were 121 esophageal cancer patients who underwent curative surgery for thoracic submucosal ESCC at three Japanese hospitals. DNA was extracted from blood samples, and the C-reactive protein (CRP) 1846C>T genetic polymorphism (rs1205) was investigated using polymerase chain reaction-restriction fragment length polymorphism. We then evaluated the value of CRP 1846C>T polymorphism for diagnosis of lymph node metastasis. RESULTS: Forty-nine (40 %) patients had lymph node metastasis. The CRP 1846 C/T genotype was C/C in 19 patients, C/T in 57 patients, and T/T in 45 patients. Fisher's exact analysis of the CRP 1846C>T polymorphism showed a significantly higher frequency of lymph node involvement with the T/T genotype. Univariate and multivariate logistic regression models revealed that patients carrying the 1846 T/T genotype had a significantly greater likelihood of developing lymph node metastasis (odds ratio >2.6). Combining the CRP 1846 C/T genotype with clinical diagnosis, mainly using CT, brought a negative predictive value of 80 % to diagnosing lymph node involvement. CONCLUSIONS: CRP genetic polymorphism may be a novel predictor of risk of lymph node metastasis in ESCC, which could enable better evaluation of the necessity for lymph node dissection.

BACKGROUND: The aim of this study was to determine whether baseline C-reactive protein (CRP) levels and CRP kinetics predict the overall survival in metastatic nasopharyngeal carcinoma (mNPC) patients. METHODS: A total of 116 mNPC patients from January 2006 to July 2011 were retrospectively reviewed. Serum CRP level was measured at baseline and thereafter at the start of each palliative chemotherapy cycle for all patients. RESULTS: Patients with higher values of baseline CRP (>/= 3.4 mg/L) had significantly worse survival than those with lower baseline CRP values (< 3.4 mg/L). Patients were divided into four groups according to baseline CRP and CRP kinetics: (1) patients whose CRP < 3.4 mg/L and never elevated during treatment; (2) patients whose CRP < 3.4 mg/L and elevated at least one time during treatment; (3) patients whose CRP >/= 3.4 mg/L and normalized at least one time during treatment; and (4) patients whose CRP >/= 3.4 mg/L and never normalized during treatment. The patients were further assigned to non-elevated, elevated, normalized, and non-normalized CRP groups. Overall survival rates were significantly different among the four groups, with three-year survival rates of 68%, 41%, 33%, and 0.03% for non-elevated, elevated, normalized, and non-normalized CRP groups respectively. When compared with the non-elevated group, hazard ratios of death were 1.69, 2.57, and 10.34 in the normalized, elevated, and non-normalized groups (P < 0.001). CONCLUSIONS: Baseline CRP and CRP kinetics may be useful to predict the prognosis of metastatic NPC patients treated with palliative chemotherapy and facilitate individualized treatment. A prospective study to validate this prognostic model is still needed however.

BACKGROUND: Squamous cell carcinoma antigen (SCC-Ag) level and C-reactive protein (CRP) have been shown to be associated with tumor invasion, lymph node metastasis, staging and survival in patients with oral squamous cell carcinoma (OSCC). The purpose of the present study was to analyze the relationship between preoperative levels of both SCC-Ag and CRP, with clinicopathologic factors and prognosis in OSCC patients. METHODS: A retrospective study was performed on 142 OSCC patients between March 2008 and March 2011. Their serum SCC-Ag and CRP levels were measured preoperatively. RESULTS: SCC-Ag level of >/=2.0 ng/ml and CRP level >/=5.0 mg/L were significantly associated with pathologic tumor status (P < 0.001), pathologic nodal metastasis (P = 0.001), tumor depth (>/=10 mm vs. <10 mm, P < 0.001), disease-free survival (P tumor status, lymph node metastasis and tumor cell differentiation. CONCLUSIONS: Concurrent high levels of both preoperative SCC-Ag and CRP levels act as a predictor for lymph node metastasis, advanced tumor stage and tumor recurrence. It therefore has significant potential as a biomarker for risk stratification in OSCC.

Growing evidence points to a role for inflammation in prostate carcinogenesis. The significance of C-reactive protein (CRP), an inflammatory and innate immunity molecule, has not been evaluated thoroughly in prostate cancer (PC). In this study of 739 Finnish patients with PC and 760 healthy men, we evaluated the associations of CRP genotypes and haplotypes with total PC risk and PC progression, using prostate-specific antigen (PSA) as a marker of metastatic disease. Although the haplotype frequencies were similar in patients and controls, an association between haplotype ACCCA and patients' PSA levels was found. The carriers more often had a high PSA than non-carriers (P=0.0002) and the SNP rs2794521 A-allele and rs1800947 C-allele carriers had a higher PSA than non-carriers (P=0.009 and P=0.0004, respectively). A trend for a younger age at diagnosis was found among the carriers of ACCCA (P=0.07) and the rs1800947 C-allele (P=0.06), as well as a trend for the latter to have more likely metastases (P=0.06), but not after Bonferroni correction (alpha=0.00208). This is the first study to suggest association between PSA and CRP variants in PC and, therefore, further studies are warranted. CRP alleles previously found to protect against increased CRP levels are now suggested to be associated with metastatic PC, indicated by elevated PSA.

OBJECTIVE: C-reactive protein (CRP) is considered a useful serum marker for patients with RCC. However, its clinical utility in advanced metastatic renal cell carcinoma (AM-RCC), particularly in deciding whether to perform nephrectomy at the onset, is not well studied. PATIENTS AND METHODS: We retrospectively evaluated 181 patients with AM-RCC, including 18 patients underwent potentially curative surgery, 111 underwent cytoreductive nephrectomy, and 52 received medical treatment only. CRP cutoff points were determined by receiver operating characteristic (ROC) curve analysis. Kaplan-Meier and Cox regression analyses were used for survival tests. RESULTS: ROC analysis suggested that grouping patients according to 3 CRP ranges was a rational model. Patients with highly elevated CRP (>/=67.0 mg/L) presented remarkably poor prognosis despite treatment (nephrectomy or medical treatment only). Cox regression models demonstrated that risk factors of overall survival for patients who underwent nephrectomy were the CRP ranges defined in this study (18.0 and <67.0 mg/L, and >/=67.0 mg/L), ECOG PS (0, 1, and >/=2), and number of metastatic organ sites (0-1 and >/=2). The retrospective design is a limitation of this study. CONCLUSION: Our study demonstrated that the serum CRP level is a statistically significant prognostic parameter for patients with AM-RCC. The data also indicated that pretreatment serum CRP level provides useful prognostic information that helps in deciding whether to perform initial nephrectomy for patients with AM-RCC.

BACKGROUND: C-reactive protein (CRP) was an independent prognostic factor for metastatic renal cell carcinoma in the cytokine era. However, the impact of CRP on the survival of metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitors has not yet been investigated. Therefore, we further evaluated the prognostic impact of CRP for patients with metastatic renal cell carcinoma treated with molecular-targeted agents of tyrosine kinase inhibitors. METHODS: Fifty-two patients were treated with tyrosine kinase inhibitors for metastatic renal cell carcinoma at our institution. Overall, 31 and 21 patients were administered sunitinib and sorafenib, respectively. The prognostic value of all variables, including CRP, for overall survival was assessed using the Cox proportional hazards model. RESULTS: The median baseline CRP level was 4.9 mg/l. In multivariate analysis, CRP was an independent predictor for overall survival as both continuous and categorical variable. The median overall survival times of patients with non-elevated CRP concentration (<8 mg/l) were not reached, compared with those of patients with elevated CRP concentration (8 mg/l or greater) of 15.9 months. There was a significant difference in overall survival rates between the two groups, with 1- and 3-year overall survival rates of 92.8 and 69.3% versus 50.2 and 22.9% for the non-elevated CRP group and the elevated CRP group (p = 0.003), respectively. CONCLUSIONS: CRP has a significant impact on overall survival of patients with metastatic renal cell carcinoma carcinoma treated with tyrosine kinase inhibitors.