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Background: Tumor‐associated immune factors are heterogeneous and play an important role in determining outcome in cancer patients. In this study, the expression levels of immune factors in tumor tissue‐conditioned media from lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) were analyzed. Methods: LUAD and LUSC tissue specimens were collected immediately after surgery for antibody array analysis and real‐time quantitative PCR. Results: Higher levels of chemokines MCP1/CCL2 (21.11‐fold increase) and MIP‐1β/CCL4 (19.33‐fold increase) were identified in LUAD than in LUSC. Western blot and quantitative real‐time PCR analyses showed higher co‐expression of CCL2 and CCL4 in LUAD tissues compared to LUSC (P < 0.0001). Immunofluorescent co‐staining showed a high percentage of CCL2+/CD68+ and CCL4+/CD68+ tumor‐associated macrophages in LUAD compared to LUSC tissues, which might be responsible for the higher expression of CCL2 and CCL4 in LUAD samples. Kaplan–Meier curves showed that CCL2 overexpression in patients with LUSC was associated with beneficial overall survival (OS; P = 0.048) and progression‐free survival (PFS; P = 0.012); however, LUAD patients with higher CCL2 expression had unfavorable OS (P = 6.7e−08) and PFS (P = 0.00098). Similarly, CCL4 overexpression predicted favorable PFS (P = 0.021) in patients with LUSC, but patients with high CCL4 levels in LUAD had shorter OS (P = 0.013). Conclusion: Our study revealed that CCL2 and CCL4 expression levels could serve as potential prognostic biomarkers and therapeutic targets for NSCLC patients. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Profiling of Epstein-BarrVirus-Encoded MicroRNAs inNasopharyngeal CarcinomaReveals Potential Biomarkersand Oncomirs," by Wong AM, Kong KL and colleagues is presented and also includes the reply from the author.

BACKGROUND: Epstein-Barr virus (EBV) microRNAs are abundant in nasopharyngeal carcinoma (NPC) tumors. With recent advances in serum microRNA detection, the distinct presence of EBV microRNAs in serum could aid in screening endemic regions for NPC. A proposed network of genes targeted by these microRNAs could also shed light on EBV-associated tumorigenesis. METHODS: MicroRNA microarray profiling of 5 paired NPC biopsies was followed by validation of 12 up-regulated EBV microRNAs (BART1-3p, 2-5p, 5, 6-5p, 6-3p, 7, 8, 9, 14, 17-5p, 18-5p, 19-3p) in 15 additional cases by real-time polymerase chain reaction. Tumor (cellular) and serum microRNA copy numbers from the same 15 patients were correlated. Expression of the same microRNAs were also examined in EBV-positive cell lines C666 and NP460hTERT+EBV. Bioinformatic tools helped predict cellular target genes, which were later confirmed by gene expression analysis. RESULTS: The authors' high-throughput approach shows that EBV microRNAs are generally more up-regulated than microRNAs of human origin. Twenty-nine of 39 EBV microRNAs were significantly up-regulated in tumor versus their nontumor biopsies ( P < .05). Upon successfully validating 12 selected EBV microRNAs in 15 additional paired NPC cases, the authors found that their distinct presence in the serum of NPC patients positively correlated with cellular copy numbers of EBV microRNAs. Further investigation of potential EBV microRNA target genes revealed inhibition of tumor suppressor genes (eg, PTEN) and extensive deregulation of several pathways frequently involved in NPC (eg, Wnt signaling). CONCLUSIONS: Increasing knowledge of host-virus interaction via microRNAs may provide feasible explanations underlying NPC tumorigenesis along with the development of biomarkers for screening high-risk populations. Cancer 2012;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]