Gene expression-based immune infiltration analyses of renal cancer and their associations with survival outcome.

BACKGROUND: Renal cancer is a common malignant tumor with an increasing incidence rate. METHODS: In this study, based on the gene expression profiles, we analyzed the compositions of tumor-infiltrating immune cells (TIICs) in renal cancer and paracancerous samples using CIBERSORT. The proportions of 22 TIICs subsets in 122 paired renal carcinoma and paracancerous samples, and 224 Wilms tumor (WT) samples varied between intragroup and intergroup. RESULTS: After analyzed the difference of TIICs composition between renal cancer and paired paracancerous samples, we found that M0 macrophages and CD8 T cells were significantly elevated, while naive B cells were significantly decreased in renal cancer samples compared with paracancerous samples. Survival analysis showed that high overall TIICs proportion, the low proportion of resting mast cells and the high proportion of activated memory CD4 T cells were associated with poor prognosis of renal cancer patients. In addition, 3 clusters were identified by hierarchical clustering analysis, and they presented a distinct prognosis. Cluster 1 had superior survival outcomes, while cluster 2 had an inferior survival outcome. CONCLUSIONS: Our study indicated that overall TIICs proportion, certain TIICs subset proportion, including resting mast cells and activated memory CD4 T cells, and distinct cluster patterns were associated with the prognosis of renal cancer, which was significant for the clinical surveillance and treatment of renal cancer.

Clinical value of combined serum CA125, NSE and 24-hour urine VMA for the prediction of recurrence in children with neuroblastoma.

BACKGROUND: In this study, we intend to retrospectively analyze the clinical data of postoperative neuroblastoma children, including the results of follow-up examinations and laboratory tests, to explore the clinical value of combined serum Carbohydrate antigen 125 (CA125), neuron-specific enolase (NSE) and 24-hour urine vanillylmandelic acid (VMA) levels at baseline for the prediction of recurrence in children with neuroblastoma. METHODS: 265 children with neuroblastoma were successfully followed up, including 163 cases without recurrence (non-recurrence group) and 102 cases with recurrence (recurrence group). The levels of 24-hour urine VMA were determined using spectrophotometric methods. Additionally, the serum levels of CA125 and NSE were measured using electrochemiluminescence immunoassay. RESULTS: The serum CA125, NSE and 24-hour urine VMA levels were significantly higher in the recurrence group than in the non-recurrence group. It demonstrated a significant positive correlation between the levels of serum CA125, NSE, and 24-hour urine VMA in all children with neuroblastoma. All children in stage IV of neuroblastoma had the highest level of serum CA125, NSE and 24-hour urine VMA and vice versa. The combined CA125, NSE and VMA had significantly better sensitivity and specificity than an individual marker. CONCLUSIONS: Combined serum CA125, NSE and 24-hour urine VMA had the potential to predict neuroblastoma recurrence more effectively.

Effects of Surgery Combined with Different Chemotherapy on Matrix Metalloproteinase-9 and Tissue Inhibitors of Metalloproteinase-1 in Children with Neuroblastoma.

Background: Neuroblastoma (NB) is a common extracranial malignancy in children and accounts for 15% of all cancer-related deaths in children, with the 5-year survival of patients in an advanced stage being lower than 40%. Preoperative adjuvant chemotherapy has been reported to facilitate surgical resection and improve the 2-year survival of patients. Objective: To analyze the efficacy of surgery plus different chemotherapy on children with NB and to investigate the correlation of matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of metalloproteinase-1 (TIMP-1) with chemotherapy efficacy. Methods: From April 2005 to May 2017, a total of 92 cases of NB treated in our hospital were assessed for eligibility and recruited. They were assigned at a ratio of 1: 1 to receive either CAV (cyclophosphamide + vincristine + adriamycin) (group A) and EP (etoposide + cisplatin) alternately or TOPO (topotecan) + CTX (cytoxan) + CiE (etoposide + cisplatin) + CPV (cyclophosphamide + pirarubicin + vincristine) (group B). The outcome measures include chemotherapy efficacy, surgical resection rates, complications, 2-year recurrence, and 2-year survival. The levels of NK cells, CD4+/CD8+ cells, MMP-9, TIMP-1, and urine catecholamine (VMA) in peripheral blood of patients before and after initial chemotherapy were determined to analyze the correlation of MMP-9, TIMP-1, and VMA with the efficacy of chemotherapy. Results: The two groups had similar efficacy (84.00% vs. 95.24%) and surgical resection rates (60.00% vs. 61.90%) after the initial chemotherapy (P > 0.05). Surgery for all eligible patients was successful after second chemotherapy. All eligible patients showed myelosuppression after chemotherapy, including 48 cases with stages I-II (52.17%) and 44 cases with stages III-IV (47.83%). The ratio of CD4+/CD8+ cells, MMP-9, TIMP-1, and VMA expression levels in peripheral blood of patients decreased (P < 0.05) after chemotherapy, and the ratio of CD4+/CD8+ cells was further reduced after surgery (P < 0.05), while natural killer (NK) cells levels increased (P < 0.05). However, intergroup differences were absent in the incidence of myelosuppression, CD4+/CD8+ cell ratio, NK cells, MMP-9, TIMP-1, and VMA expression levels (P > 0.05). MMP-9 and TIMP-1 were positively correlated with VMA (P < 0.05), and the expression levels of MMP-9 and TIMP-1 and VMA after chemotherapy were negatively correlated with chemotherapy efficiency (P < 0.05). Patients with high expressions of MMP-9, TIMP-1, and VMA were associated with lower 2-year survival versus those with low expressions (P < 0.05). Conclusion: Surgery plus chemotherapy for children with NB yields a promising clinical efficacy and a favorable surgical resection outcome. MMP-9 and TIMP-1 may be the potential biological indicators for chemotherapy efficiency and have a reference value for following surgical treatment of patients.

Gene expression-based immune infiltration analyses of liver cancer and their associations with survival outcomes.

INTRODUCTION: Liver cancer is one of the most lethal malignancies, presenting inferior survival outcomes once diagnosed. Current therapeutic approaches mainly target the tumor cells or vasculature, but rarely take the immune factors into consideration. METHODS: In our study, the compositions of tumor-infiltrating immune cells (TIICs) in liver cancer and paracancer samples were analyzed based on the gene expression profiles by CIBERSORT. After calculating the proportions of 22 TIICs subtypes in 51 paired cancer and paracancer samples, we found their proportions varied between intragroup and intergroup. Compared with the paracancer tissues, the relative proportions of macrophages M0 and resting mast cells in liver cancer samples were significantly elevated, while that of M2 macrophages were reduced. RESULTS: Univariate Cox regression analysis with the 22 TIICs subtypes as continuous variables showed increased B cells memory and resting NK cells were significantly associated with poor survival outcome. Besides, hierarchical clustering analysis based on the proportions of 22 TIICs subtypes identified 3 clusters, which exhibited distinct prognosis. Among them, cluster 1 had superior survival outcomes, while cluster 3 had inferior survival outcomes. CONCLUSIONS: Collectively, our research suggested certain TIICs subpopulations proportions, as well as cluster patterns were associated with the prognosis of liver cancer, which provided potential therapeutic targets for liver cancer.