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with benign diseases16).In this study, we hypothesized that serum LR11 level should rise in esophageal cancer patients, and examined the expression of LR11 in the serum of patients to evaluated the clinical significance of LR11. Thereby, the high serum LR11 level group had a significantly worse prognosis compared to the low LR11 group.Firstly, the serum levels of patients with esopha-geal cancer were 6.86 ± 3.68 ng/mL; this value was relatively low when compared to values for patients with non-Hodgkin’s lymphoma (17.7 ± 22.6 ng/mL), acute lymphocytic leukemia (73.5 ± 93.5 ng/mL), and acute myeloid leukemia (26.8 ± 29.1 ng/mL), where LR11 is already used as a biomarker15-25). It can be said that the value of serum LR11 in patients with esophageal cancer was lower than people without disease because the mean value of serum LR11 was reported to be around 10 as described above. We speculated that it was from patients’ malnutrition because serum LR11 was related to metabolism of cholesterol and patients with esophageal cancer often become undernour-ished caused from esophageal stenosis. We compared LR11 levels with TP/ Alb, which reflects the nutritional status of the patient, and TG/ T-Cho, which reflects lipid metabolism in the patient; however, the results showed no significant differences. Therefore, we suspect that relatively low level of LR11 might be from differences between gastrointestinal solid cancers and hemato-logical malignancies26). Recently, in patients with bile tract cancer and pancreatic cancer, bile sLR11 suggested to release from the cancer cell, and may reflect the characteristics of the microenvironment such as hypoxic conditions, and rapid cell prolifera-tion14-16). Similarly, esophageal cancer might be affected by their microenvironment, so that it needs further study.Based on our data, the level of serum LR11 are likely to be related to pT status, but not associated with pN, lymphovascular invasion, and other nutri-tional or lipid markers in blood. It is interesting that only pT status is likely to be related to serum LR11 because most prognostic biomarkers tend to be related to other significant prognostic markers like pT, pN, and lymphovascular invasions. We speculate that serum LR11 might not be related to the malignant potential but might be related to other factors such as size of tumors which could be influenced by food intake. In this study, we were not able to get information about how much weight patients lost before esophagectomy. This study has some limitations. First, this study utilized a retrospective design. Second, the sample size was very small, and short period of observa-tion. Moreover, the effect of another clinical features like adjuvant therapy, hyperlipidemia, and athero-sclerosis need to be validated. Further, pathological evaluation of LR-11 expression in tumor tissue remains to be clarified, too.In Conclusion, LR11 could be measured using the relatively simple ELISA method and is expected to be used as a new prognostic predictor for esopha-geal cancer.The authors would like to thank Professor H. Bujo for technical support with the experiments. The author(s) received no financial support for the research.TU corrected blood samples, interpreted the patient data, and was a major contributor in writing the manuscript. The article was revised by MN and all authors read and approved the final manuscript.The authors declare that they have no conflict of interest. 1） Nishii K, Nakaseko C, Jiang MZ, et al: The Soluble Form of LR11 Protein Is a Regulator of Hypoxia-induced, Urokinase-type Plasminogen Activator Receptor (uPAR)-mediated Adhesion of Immature Hematolog-ical Cells. J Biol Chem, 2013; 288: 11877-11886. 2） Liu CX, Musco S, Lisitsina NM, Forgacs E, Minna JD, Lisitsyn NA: LRP-DIT, a putative endocytic receptor gene, is frequently inactivated in non-small cell lung cancer cell lines. Cancer Res, 2000; 60: 1961-1967. 3） Sonoda I, Imoto I, Inoue J, et al: Frequent silencing of low density lipoprotein receptor-related protein 1B (LRP1B) expression by genetic and epigenetic mech-anisms in esophageal squamous cell carcinoma. Cancer Res, 2004; 64: 3741-3747. 4） Matsuo M, Ebinuma H, Fukamachi I, Jiang M, Bujo H, Saito Y: Development of an immunoassay for the quan-tification of soluble LR11, a circulating marker of 519AcknowledgementsFundingAuthor contributionsConflicts of interest statementReferences