Positive lymph node ratio predicts adverse prognosis for patients with lymph nodes metastatic hypopharyngeal squamous cell carcinoma after primary surgery.

Background: Positive lymph node ratio (LNR) is associated with the prognosis of many cancers. However, its prognostic value in patients with hypopharyngeal squamous cell carcinoma (HSCC) is unclear due to the rarity of HSCC. This study aimed to investigate the prognostic value of LNR in HSCC using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Data spanning 2004 to 2015 of eligible HSCC patients were retrospectively retrieved from the SEER database. Clinicopathological data, including age at diagnosis, race, gender, marital status, primary tumor site, tumor size, tumor grade, Tumor-Lymph Node-Metastasis (TNM) stage, surgical type, postoperative adjuvant therapy (POAT) record, the number of lymph nodes (LNs) examined, the number of positive LNs, survival time, and death classification were collected and dichotomized through the receiver operating characteristic (ROC) curve. The LNR was defined as the ratio of positive LNs to the total number of LNs examined. The Kaplan-Meier method and Cox regression models were used to assess the association between LNR vs. cancer-specific survival (CSS) and overall survival (OS). Results: The 5-year CSS and OS rates of the 391 patients were 44% and 33.7%, respectively. The median LNR was 0.083 [interquartile range (IQR), 0.043-0.179], and the optimal cut-off value of LNR was 0.23. Kaplan-Meier curves showed that patients with LNR ≥0.23 had significantly shorter CSS and OS than LNR <0.23. In multivariable analysis, large tumor size [hazard ratio (HR): 1.012, P=0.016], N3 stage (HR: 2.113, P=0.040), M1 stage (HR: 2.458, P=0.041), with POAT (HR: 0.559, P=0.001), and LNR ≥0.23 (HR: 1.795, P=0.001) independently predicted CSS, while old age (HR: 1.019, P=0.009), large tumor size (HR: 1.012, P=0.006), M1 stage (HR: 3.422, P=0.001), with POAT (HR: 0.610, P=0.001), and LNR ≥0.23 (HR: 1.667, P=0.001) independently predicted OS. The subgroup analysis showed that patients with LNR ≥0.23 shared worse CSS and OS in either N2 or N3 subgroups than those with LNR <0.23. Furthermore, POAT provided an independent protective factor in the LNR ≥0.23 group, while it had no significant effect in the LNR <0.23 group. Conclusions: This study demonstrates a strong association between LNR and prognosis in patients with LNs metastatic HSCC. Further, it provides an alternative tool for providing supplemental information regarding prognosis.

Establishment of a patient-derived organoid model and living biobank for nasopharyngeal carcinoma.

Background: Recurrent nasopharyngeal carcinoma (NPC) remains a major challenge for clinicians and scientists. Tumor organoid is a revelational disease model that highly resembled the heterogeneity and histopathological characteristics of original tumors. This study aimed to optimize the modeling process of patient-derived NPC organoids (NPCOs), and establish a living-biobank of NPCs to study the mechanism and explore the more effective treatment of the disease. Methods: Sixty-two fresh NPC tissue samples and 15 normal mucosa samples were collected for 3-dimensional (3D) organoid culture. The organoids were confirmed using hematoxylin and eosin assays. The expression levels of CD133, CD44, BMI-1, and Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) were detected by immunohistochemistry (IHC) and in situ hybridization (ISH). Recurrent NPCOs were frozen in liquid nitrogen for 6 months and then resuscitated and passaged. Results: We identified a novel two-step enzymatic strategy for the treatment of NPC and nasal mucosa specimens and an optimal medium for culturing NPCOs and nasal mucosa organoids (NMOs). Organoid cultures were generated from 34 primary NPC samples, 28 recurrent NPC samples, and 15 normal mucosa samples. The success rates for primary NPCO, recurrent NPCO, and NMO formation were 47.06%, 81.25%, and 86.5%, respectively. All the NPCOs were EBER positive and CK7 negative. Recurrent NPCOs had higher expressions of stem cell markers, including BMI-1, CD44, and CD133. Additionally, recurrent NPCOs could be cultured to passage 4 and frozen and revived repeatedly, while primary NPCOs were challenging to culture. Conclusions: In summary, we successfully established a living biobank using the NPCO model, which has enormous potential in basic and clinical research on NPC.

Comparing endoscopic surgeries with open surgeries in terms of effectiveness and safety in salvaging residual or recurrent nasopharyngeal cancer: Systematic review and meta-analysis.

Consensus has yet to be reached on the optimal operation for patients with residual or recurrent nasopharyngeal carcinoma (NPC). To compare effectiveness and safety of open surgery and endoscopic surgery for patients with residual or recurrent NPC. Pubmed, Embase, and Cochrane were searched for relevant publications from January 1, 2000 to May 1, 2017. Included studies reported specific residual or local recurrent nasopharyngeal cancer survival data. Proportional meta-analysis was performed on both outcomes with a random-effects model, and the 95% confidential intervals were calculated by Stata 12.0 software. For patients with different tumor classification, a downward trend of 2-year overall survival (OS) was observed for both surgical populations. Endoscopic surgeries achieved bigger rates than open surgeries in patients with recurrent tumor (rT) 1, rT2, and rT3 (93% vs 87%, 77% vs 63%, 67% vs 53%). As for patients with rT4, 2-year OS was similar (35% vs 35%).In addition, the former is less severe complications, lower local recurrence rates (27% vs 32%). Our study found that, compared to open surgery, endoscopic surgery was a safer and more effective treatment modality in managing patients with recurrent or residual NPC.

MicroRNA-200a Promotes Phagocytosis of Macrophages and Suppresses Cell Proliferation, Migration, and Invasion in Nasopharyngeal Carcinoma by Targeting CD47.

Nasopharyngeal carcinoma (NPC) causes severe oncogenic lesions in the nasopharynx. CD47, a transmembrane integrin-associated protein, plays a key role in the ability of tumor cells to escape phagocytosis, working as an immune checkpoint in the immune response. Besides this role, CD47 has been reported to regulate cell proliferation and migration. The present study addresses the relationship between CD47 and microRNA-200a and examines their regulatory mechanisms in NPC. Bioinformatics analyses and dual-luciferase reporter assays were used to confirm the putative relationship between miR-200a and CD47, and their interaction was further detected using western blotting and RT-PCR. Further, results showed that miR-200a affect NPC cell proliferation, migration, and invasion by regulating CD47. A cell phagocytosis assay showed that miR-200a and a CD47 monoclonal antibody increased the sensitivity of NPC cells to macrophage phagocytosis by inhibiting the functions of CD47. Additionally, miR-200a expression was suppressed and CD47 expression increased in both clinical NPC tissues and cell lines. Taken together, these results show the miR-200a/CD47 combination as a potential therapeutic for treatment of NPC.

LncRNA UCA1 affects epithelial-mesenchymal transition, invasion, migration and apoptosis of nasopharyngeal carcinoma cells.

Objective: In this study, long non-coding RNA urothelial carcinoma associated 1 (lncRNA UCA1) in nasopharyngeal carcinoma (NPC) and its effect on the malignant phenotype of NPC cells was investigated. Methods: Initially, the expression of UCA1 in NPC tissues and cells was detected. NPC cell line that with highest expression of UCA1 was selected for subsequent cell function test. A series of experiments were used to detect proliferation, colony formation, cell cycle distribution, apoptosis, invasion and migration of NPC cells with the interference of UCA1 expression. Western blot analysis was carried out to detect the expression of E-cadherin and vimentin for verifying the effect of UCA1 on epithelial mesenchymal transition (EMT). Results: The expression of UCA1 was found to be upregulated in NPC tissues and cells. The expression of UCA1 in stage Ⅲ + IV of NPC tissues and in patients with lymph node metastasis was significantly higher than that in patients at stage Ⅰ + Ⅱ and in patients without lymph node metastasis. Inhibition of UCA1 repressed proliferation, EMT, colony formation, invasion and migration while stimulating apoptosis of NPC cells. Conclusion: Our study suggests that UCA1 expression was overexpressed in NPC. Additionally, UCA1 suppression could inhibit proliferation, EMT, invasion and migration, and promote apoptosis of NPC cells.