Hu-antigen receptor (HuR) and cyclooxygenase-2 (COX-2) expression in human non-small-cell lung carcinoma: associations with clinicopathological parameters, tumor proliferative capacity and patients’ survival

Abstract

Hu-antigen R (HuR) is considered to play a central role in tumor formation, growth, and metastasis by binding to messenger RNAs (mRNAs) encoding proteins such as cyclooxygenase-2 (COX-2) and inducing their expression via mRNA stabilization and/or altered translation. The present study aimed to evaluate the clinical significance of HuR and COX-2 protein expression in non-small-cell lung carcinoma (NSCLC). HuR and COX-2 expression was assessed immunohistochemically on tissue microarrays of 81 surgically resected NSCLC and was analyzed in relation with clinicopathological characteristics and patients' survival. Enhanced total HuR expression was significantly associated with tumor histological type and presence of lymph node metastases, as well as with increased tumor proliferative capacity and poor patients' outcome (p = 0.039, p = 0.017, p = 0.033, and p = 0.022, respectively). Enhanced COX-2 expression was significantly associated with the presence of lymphovascular invasion and increased tumor proliferative capacity (p = 0.031 and p = 0.023, respectively). Concomitant elevated HuR/COX-2 expression levels were significantly associated with tumor histological type and increased proliferative capacity (p = 0.002 and p = 0.045, respectively). Enhanced total HuR expression, as well as its cytoplasmic localization, was significantly associated with increased COX-2 expression (p = 0.015 and p = 0.001, respectively). The present study supported evidence that HuR may participate in malignant transformation of NSCLC, reinforcing its usefulness as potential therapeutic target in this type of neoplasia.

Elevated Hu-Antigen Receptor (HuR) Expression is Associated with Tumor Aggressiveness and Poor Prognosis but not with COX-2 Expression in Invasive Breast Carcinoma Patients

“…All patients received conventional postoperative treatment depending on the extent of the disease, including adjuvant chemotherapy, radiation therapy and anti-estrogen therapy, when indicated, according to the consensus recommendations at the time [35]. [19,36]. A mouse anti-human Ki-67 antigen; IgG1k antibody (clone MIB-1, Dakopatts, Glostrup, Denmark) were used to evaluate the tumor cells' proliferative capacity [36,37].…”

“…Finally, HuR and COX-2 expression was classified as low; if the total score was 0 or 2 and high; if the total score was ≥3. In this way, we ensure that each group has a more homogeneous and sufficient number of cases in order to be comparable with the other groups [19,36,37,39]. Staining for ER and PR was evaluated according to CAP/ ASCO recommendations, i.e.…”

“…The fraction of HER2 positive stained cells was scored according to CAP/ASCO guidelines [41]. Ki-67 immunoreactivity was classified according to the percentage of positively stained breast cancer cells exceeded the median percentage value into two categories (below and over mean value), as previously reported [19,36,37,39].…”

“…The most comprehensive studies so far have supported substantial evidence that HuR is implicated in several pathological conditions, such as atherosclerosis [16], tissue ischemia [17], pathologic inflammation [6] and neoplasia [15,18,19]. Notably, HuR has been suggested to participate in malignant transformation process by controlling cancerrelevant genes related with angiogenesis, differentiation, cell cycle, apoptosis, inflammatory response and cell signaling [15,[18][19][20][21].…”

“…Notably, HuR has been suggested to participate in malignant transformation process by controlling cancerrelevant genes related with angiogenesis, differentiation, cell cycle, apoptosis, inflammatory response and cell signaling [15,[18][19][20][21]. Moreover, HuR appears to exert a critical role in tumor formation, growth and metastasis by binding to mRNA encoding proteins and by affecting their expression via mRNA stabilization and/or altered translation [15,20,21].…”