In lung adenocarcinoma, the IASLC/ATS/ERS classification system has significant prognostic and predictive value regarding death and recurrence. Solid-predominant adenocarcinoma was also a significant predictor in patients undergoing adjuvant chemotherapy. Prognostic and predictive information is important for stratifying patients for aggressive adjuvant chemoradiotherapy.

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The C-type lectin member 5A (CLEC5A) is a pattern recognition receptor for members of the Flavivirus family and has critical functions in response to dengue virus and Japanese encephalitis virus. Here we show that CLEC5A is involved in neutrophil extracellular trap formation and the production of reactive oxygen species and proinflammatory cytokines in response to Listeria monocytogenes. Inoculation of Clec5a −/− mice with L. monocytogenes causes rapid bacterial spreading, increased bacterial loads in the blood and liver, and severe liver necrosis. In these mice, IL-1β, IL-17A, and TNF expression is inhibited, CCL2 is induced, and large numbers of CD11b+Ly6ChiCCR2hiCX3CR1low inflammatory monocytes infiltrate the liver. By day 5 of infection, these mice also have fewer IL-17A+ γδ T cells, severe liver necrosis and a higher chance of fatality. Thus, CLEC5A has a pivotal function in the activation of multiple aspects of innate immunity against bacterial invasion.

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Tumor recurrence is the most common cause of disease failure after surgical resection in early-stage lung adenocarcinoma. Identification of clinically relevant prognostic markers could help to predict patients with high risk of disease recurrence. A meta-analysis of available lung adenocarcinoma microarray datasets revealed that T-LAK cell-originated protein kinase (TOPK), a serine/threonine protein kinase, is overexpressed in lung cancer. Using stable cell lines with overexpression or knockdown of TOPK, we have shown that TOPK can promote cell migration, invasion, and clonogenic activity in lung cancer cells, suggesting its crucial role in lung tumorigenesis. To evaluate the prognostic value of TOPK expression in resected stage I lung adenocarcinoma, a retrospective analysis of 203 patients diagnosed with pathological stage I lung adenocarcinoma was carried out to examine the expression of TOPK by immunohistochemistry (IHC). The prognostic significance of TOPK overexpression was examined. Overexpression of TOPK (IHC score >3) was detected in 67.0% of patients, and these patients were more frequently characterized with disease recurrence and angiolymphatic invasion. Using multivariate analysis, patient age (>65 years old; P = 0.002) and TOPK overexpression (IHC score >3; P < 0.001) significantly predicted a shortened overall survival. Moreover, TOPK overexpression (IHC score >3; P = 0.005) also significantly predicted a reduced time to recurrence in the patients. Our results indicate that overexpression of TOPK could predetermine the metastatic capability of tumors and could serve as a significant prognostic predictor of shortened overall survival and time to recurrence. (Cancer Sci 2012; 103: 731-738) L ung cancer is the leading cause of cancer-related death worldwide. The incidence of adenocarcinoma, the most common histological subtype of non-small-cell lung carcinoma (NSCLC) in most countries, has increased in both sexes during the past several decades, whereas squamous cell carcinoma has decreased.(1,2) Surgical resection is the main treatment of choice for early-stage NSCLC.(3) Although patient survival after stage I NSCLC resection is good, postoperative recurrence has been reported to occur in 22-38% of patients. The survival rate is poor in patients with recurrence following resection of stage I NSCLC. (6,8) Many randomized clinical trials have evaluated the role of adjuvant chemotherapy in patients with resected stage I NSCLC and have tried to identify patients with a higher risk of recurrence or poor prognosis after surgical resection.(9-11) Investigation of biomarkers of early-stage NSCLC may be helpful in designing clinical trials for adjuvant chemotherapy in the future. T-LAK cell-originated protein kinase (TOPK), also known as PDZ-binding kinase (PBK), is a MAPKK-like serine/threonine protein kinase that was identified as an interleukin-2-induced gene in T-LAK cells and as an interaction partner with the human tumor suppressor hDlg, identified by yeast two-hybrid screening. (12,13) TOPK is bar...