BackgroundMetabolome analysis including amino acid profile is under investigation as an approach in cancer screening. The present study aims to analyze plasma free amino acid (PFAA) profiles in cancer patients and investigate their potential as biomarkers of malignancy.MethodsPlasma samples from 56 gastric cancer patients, 28 breast cancer patients, 33 thyroid cancer patients, and 137 age-matched healthy controls were collected in the study. PFAA levels were measured and their perioperative alterations were analyzed. Biological effects of ten cancer-related amino acids were further validated in gastric and breast cancer cells.ResultsWe found that PFAA profiles of cancer patients differed significantly from those of healthy controls. Decreased concentrations of PFAAs were associated with lymph node metastases in gastric cancer. Levels of PFAAs such as aspartate and alanine increased after tumor resection. PFAA levels correlated with clinical tumor markers in gastric cancer patients and pathological immunohistochemistry markers in breast cancer patients. Specifically, alanine, arginine, aspartate and cysteine had proliferative effects on breast cancer cells. Proliferation of gastric cancer cells was promoted by cysteine, but inhibited by alanine and glutamic acid. Furthermore, alanine treatment decreased total and stable fraction of gastric cancer cells, and alanine and glutamic acid induced apoptosis of gastric cancer cells.ConclusionsPFAA patterns in cancer patients are altered perioperatively. Tumor-related amino acids identified by dynamic study of PFAA patterns may have the potential to be developed as novel biomarkers for diagnosis and prognosis of cancer patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0408-1) contains supplementary material, which is available to authorized users.

Nuclear genetic alterations have been widely investigated in papillary thyroid cancer (PTC), however, the characteristics of the mitochondrial genome remain uncertain. We sequenced the entire mitochondrial genome of 66 PTCs, 16 normal thyroid tissues and 376 blood samples of healthy individuals. There were 2508 variations (543 sites) detected in PTCs, among which 33 variations were novel. Nearly half of the PTCs (31/66) had heteroplasmic variations. Among the 31 PTCs, 28 specimens harbored a total of 52 somatic mutations distributed in 44 sites. Thirty-three variations including seven nonsense, 11 frameshift and 15 non-synonymous variations selected by bioinformatic software were regarded as pathogenic. These 33 pathogenic mutations were associated with older age (p = 0.0176) and advanced tumor stage (p = 0.0218). In addition, they tended to be novel (p = 0.0003), heteroplasmic (p = 0.0343) and somatic (p = 0.0018). The mtDNA copy number increased in more than two-third (46/66) of PTCs, and the average content in tumors was nearly four times higher than that in adjacent normal tissues (p < 0.0001). Three sub-haplogroups of N (A4, B4a and B4g) and eight single-nucleotide polymorphisms (mtSNPs) (A16164G, C16266T, G5460A, T6680C, G9123A, A14587G, T16362C, and G709A) were associated with the occurrence of PTC. Here we report a comprehensive characterization of the mitochondrial genome and demonstrate its significance in pathogenesis and progression of PTC. This can help to clarify the molecular mechanisms underlying PTC and offer potential biomarkers or therapeutic targets for future clinical practice.

No abstract

Marital status proved to be an independent prognostic factor for survival in patients with breast cancer. We therefore strove to explore the impact of dynamic changes in marital status on the prognosis of breast cancer patients. We selected patients meeting the eligibility criteria from the Surveillance, Epidemiology, and End Results cancer database. We then used multivariate Cox proportional hazard regression model to analyze the effect of dynamic changes in marital status on the prognosis of overall survival (OS) and breast cancer-specific special survival (BCSS). Compared with the patients in the Single–Single group and the divorced/separated/widowed–divorced/separated/widowed (DSW–DSW) group, patients in the Married–Married group were significantly associated with better BCSS (HR 1.13, 95% CI: 1.03–1.19, P < 0.001; HR 1.19, 95% CI: 1.14–1.25, P < 0.001, respectively) and OS (HR 1.25, 95% CI: 1.20–1.30, P < 0.001; HR 1.49, 95% CI: 1.45–1.54, P < 0.001, respectively). In contrast to the DSW–DSW group, the Single–Single group and the DSW–Married group showed similar BCSS (HR 0.98, 95% CI: 0.92–1.05, P = 0.660; HR 1.06, 95% CI: 0.97–1.15, P = 0.193, respectively) but better OS (HR 1.14, 95% CI: 1.09–1.19, P < 0.001; HR 1.32, 95% CI: 1.25–1.40, P < 0.001, respectively). Compared with the Single–Single group, the Single–Married group showed significantly better BCSS (HR 1.21, 95% CI: 1.07–1.36, P = 0.003) but no difference in OS (HR 1.08, 95% CI: 0.98–1.18, P = 0.102); In contrast to the Married–DSW group, the Married–Married group exhibited better BCSS (HR 1.11, 95% CI: 1.05–1.18, P < 0.001) and OS (HR 1.27, 95% CI: 1.22–1.32, P < 0.001). Our study demonstrated that, regardless of their previous marital status, married patients had a better prognosis than unmarried patients. Moreover, single patients obtained better survival outcomes than DSW patients. Therefore, it is necessary to proactively provide single and DSW individuals with appropriate social and psychological support that would benefit them.

Purpose:The clinical benefits provided by using anthracycline-contained regimens in patients with early breast cancer (EBC) remain uncertain. This meta-analysis used data from all relevant trials to compare treatment outcomes for patients with EBC receiving adjuvant chemotherapy with non–anthracycline-contained regimens or anthracycline-contained regimens.Patients and Methods:Individual patient data were collected on 7 randomized trials comparing non–anthracycline-contained regimens with anthracycline-contained regimens, a total of 14,451 women were analyzed. The hazard ratios (HR) of disease-free survival (DFS) and overall survival (OS), and the risk ratios for grades 3 to 4 toxicities were extracted from the retrieved studies and analyzed using various statistical methods. A pooled analysis was accomplished and HR with 95% confidence intervals (95% CIs) was derived. The significant differences in DFS and OS were explored. A heterogeneity test was applied as well.Results:Among 7 eligible trials, significant differences in favor of anthracycline-contained regimens were seen in DFS (HR: 0.86; 95% CI: 0.78–0.95; P = .003) and in OS (HR: 0.85; 95% CI: 0.75–0.97; P = .01). Subgroup analyses of DFS showed similar treatment effects by hormone-receptor status and nodal status, but differential effects by human epidermal growth factor receptor 2 status, menopausal status, and malignancy grade. Sensitive analysis showed that the DFS of taxanes and cyclophosphamide (TC) was noninferior to anthracycline-contained regiments.Conclusion:Despite failing to show noninferior to the anthracycline-contained regimens in patients with EBC, it provides evidence that both regimens significantly improved the DFS and OS, and TC regimen may be noninferior to anthracycline-contained regimens.