https://www.jto.org/article/S1556-0864(16)30453-1/pdf

A Proposal for Combination of Lymph Node Ratio and Anatomic Location of Involved Lymph Nodes for Nodal Classification in Non–Small Cell Lung Cancer

Breast cancers with 10 or more positive lymph nodes at the time of diagnosis are staged as pathological N3a (pN3a) and they have poor prognosis. Recent studies showed five-year disease-free survival (DFS) and overall survival (OS) rates of N3a disease as 43-66 and 58-81 %, respectively. We herein present outcomes of our patients with stage pN3a breast cancer. Among 2,578 patients diagnosed with invasive breast carcinoma at Hacettepe University Hospital between 2002 and 2012, 218 patients (8.4 %) had pN3a disease and were included and analyzed retrospectively in this study. Patients with internal mammary, infraclavicular, and supraclavicular node metastasis or distant metastasis at initial diagnosis were excluded. Demographic features, tumor characteristics, treatment regimens, and patient outcomes in terms of DFS and OS were analyzed. Lymph node ratio was defined as the ratio of positive to total removed lymph nodes. The median age was 49. Most common histological subtype was ductal carcinoma (82.1 %). About 82.6 % of patients had stage T2/T3 cancers and 47.7 % (104) had grade III cancers. Estrogen and progesterone receptors were positive in 133 (61 %) and 121 (55.5 %) patients, respectively. HER2 status was known for 213 patients and was positive in 87 (39.9 %) patients. A total of 27 (12.6 %) patients had triple-negative tumors. Lymphovascular invasion, extracapsular extension, and perineural invasion were present in 106 (48.6 %), 105 (48.2 %), 20 (9.2 %) cases, respectively. A total of 18 patients (8.3 %) received neoadjuvant and 200 patients (91.7 %) received adjuvant chemotherapy, mostly with anthracycline- (95 %) and taxane (60 %)-containing regimens. A total of 210 patients (96.3 %) received radiotherapy. Median follow-up was 39.5 months. A total of 96 patients relapsed on follow-up and 64 patients died. Nineteen of the relapses were locoregional and 77 were distant relapses. The 5-year DFS rate was 46.2 % and the OS rate was 69.8 %. In multivariate Cox regression analysis, grade III disease (HR 1.899, 95 % CI 1.196-3.017, P = 0.007), perineural invasion (HR 2.519, 95 % CI 1.341-4.731, P = 0.004), and lymph node ratio (≥ 0.9 vs. <0.9) (HR 2.290, 95 % CI 1.368-3.835, P = 0.002) were significantly associated with DFS, and grade III disease (HR 2.679, 95 % CI 1.500-4.782, P = 0.001) and lymph node ratio (≥ 0.9 vs. <0.9) (HR 2.182, 95 % CI 1.211-3.932, P = 0.009) were significantly associated with OS. Patients with pN3a disease in our cohort have comparable survival rates with other reports in the literature. Within this high risk group of patients, those with grade III disease, perineural invasion, and lymph node ratio ≥ 0.9 seem to confer poorer prognosis.

Outcomes of locally advanced breast cancer patients with ≥10 positive axillary lymph nodes

In this study, we investigated the role of microRNA-363(miR-363) in ovarian cancer (OC) progression MiR-363expression was downregulated in OC patient tissues and four OC cell lines (SKOV3, A2780, OVCAR and HO-8910) Low miR-363 levels were associated with advanced stage, lymph node metastasis, and poor prognosis in OC MiR-363 overexpression decreased growth, colony formation, migration and invasiveness of SKOV3 cells In addition, miR-363 overexpression in SKOV3 cells also decreased xenograft tumor size and weight in nude mice Bioinformatics and dual luciferase reporter assays revealed that miR-363 suppresses expression of NIN1/RPN12 binding protein 1 homolog (NOB1) by binding to the 3'-UTR of its transcript NOB1 expression inversely correlated with miR-363 levels in OC tissues Thus miR-363 appears to play a tumor suppressor role in OC by inhibiting NOB1

/pdf/microrna-363-inhibits-ovarian-cancer-progression-by-26fqrtulof.pdf

MicroRNA-363 inhibits ovarian cancer progression by inhibiting NOB1.

BACKGROUND This meta-analysis aimed to investigate the prognostic value of lymph node ratio in non-small-cell lung cancer. METHODS We searched systematically for eligible studies in PubMed, Web of Science, Medline (via Ovid) and Cochrane library through 6 November 2018. The primary outcome was overall survival. Disease-free survival and cancer-specific survival were considered as secondary outcomes. Hazard ratio with corresponding 95% confidence interval were pooled. Quality assessment of included studies was conducted. Subgroup analyses were performed based on N descriptors, types of tumor resection, types of lymphadenectomy and study areas. Sensitivity analysis and evaluation of publication bias were also performed. RESULTS Altogether, 20 cohorts enrolling 76 929 patients were included. Mean Newcastle-Ottawa Scale was 7.65 ± 0.59, indicating the studies' quality was high. The overall result showed non-small-cell lung cancer patients with lower lymph node ratio was associated with better overall survival (HR: 1.946; 95% CI: 1.746-2.169; P < 0.001), disease-free survival (HR: 2.058; 95% CI: 1.717-2.467; P < 0.001) and cancer-specific survival (HR: 2.149; 95% CI: 1.864-2.477; P < 0.001). Subgroup analysis prompted types of lymphadenectomy and the station of positive lymph node have an important effect on the prognosis. No significant discovery was found in sensitivity analysis. CONCLUSION Patients with lower lymph node ratio was associated with better survival, indicating that lymph node ratio may be a promising prognostic predictor in non-small-cell lung cancer. The type of lymphadenectomy, an adequate examined number and the removed stations should be considered for more accurate prognosis assessment.

/pdf/prognostic-value-of-lymph-node-ratio-in-non-small-cell-lung-5dzjhuk6nd.pdf

Prognostic value of lymph node ratio in non-small-cell lung cancer: a meta-analysis.

Aberrant expression of microRNA (miRNA) is important in the progression of various human cancers, however further investigation is required in order to fully elucidate mechanisms of and validate actions of endogenous non-coding RNAs. The present study demonstrated that the expression of miR-646 was downregulated in colorectal cancer tissues and cell lines. Notably, it was observed that miR-646, a tumor suppressor, inhibited colorectal cancer cell progression through directly targeting Nin one binding protein (NOB1) expression, which possesses anti-tumor properties in colorectal cancer. Furthermore, knockdown of NOB1 expression was responsible for the tumor-suppressive effect of miR-646. The findings suggest that miR-646 may act as a therapeutic target for the treatment of colorectal cancer.

/pdf/low-level-mir-646-in-colorectal-cancer-inhibits-cell-1ua0j00p4d.pdf

Low‑level miR‑646 in colorectal cancer inhibits cell proliferation and migration by targeting NOB1 expression

https://www.jto.org/article/S1556-0864(15)32787-8/pdf

The Prognostic Value of Ratio-Based Lymph Node Staging in Resected Non–Small-Cell Lung Cancer

NIN/RPN12 binding protein 1 (NOB1p) encoded by NOB1 has been found to be an essential factor in 26S proteasome biogenesis which participates in protein degradation. However, the functions of NOB1 in non-small cell lung cancer cells are largely unknown. In the present study, lentivirus-mediated NOB1 shRNA transfection in two non-small cell lung cancer cell lines (A549 and H1299) was accomplished, as determined by fluorescence imaging. Downregulation of NOB1 expression was confirmed by real-time PCR and western blotting. NOB1 silencing resulted in a significant decline in the proliferation and colony formation capability of non-small cell lung cancer cells. Moreover, flow cytometry showed that A549 cells were arrested in the G0/G1 phase of the cell cycle after NOB1 suppression. Furthermore, depletion of NOB1 resulted in a significant decrease in CDK4 and cyclin D1 expression. These results suggest that NOB1 may act as an important regulator in non-small cell lung cancer growth and could be a therapeutic target of non‑small cell lung cancer.

/pdf/lentivirus-mediated-gene-silencing-of-nob1-suppresses-non-4q7di4i6wv.pdf

Lentivirus-mediated gene silencing of NOB1 suppresses non-small cell lung cancer cell proliferation

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The Prognostic Value of Ratio-Based Lymph Node Staging in Resected Non–Small-Cell Lung Cancer

Lentivirus-mediated gene silencing of NOB1 suppresses non-small cell lung cancer cell proliferation