Clinicopathological study of malignant peripheral nerve sheath tumors in the head and neck:Case reports and review of literature

BACKGROUND Malignant peripheral nerve sheath tumor(MPNST)is a rare and aggressive soft tissue sarcoma that poses a major diagnostic and therapeutic challenge.CASE SUMMARY We retrospectively reviewed patients with head and neck MPNSTs treated in our hospital from 2000 to 2021.The clinical features,pathological manifestations,treatments,and prognoses were summarized.We also reviewed the literature,focusing on MPNST in the mandible and maxilla.The study population consisted of five women and five men aged 22–75 years(mean age,49 years).Of the 10 patients,7 were initial cases and 3 were recurrent cases.All lesions were sporadic.The most common site was the mandible.The most frequently encountered symptoms were a progressive mass and local swelling.Complete or partial loss of trimethylation at lysine 27 of histone H3(H3K27me3)was evident on staining in four of nine cases(one case was excluded due to lack of tissue for evaluation of loss of H3K27me3).The 2-and 5-year disease-specific survival rates were 86%a nd 43%,respectively.The average survival time was 64 mo.CONCLUSION MPNST is a highly malignant tumor with a poor prognosis,prone to a high risk of recurrence and distant metastasis.Complete surgical resection is the main treatment.

Lymphocyte-to-monocyte ratio predicts survival of patients with hepatocellular carcinoma after curative resection

AIM: To investigate the prognostic value of preoperative lymphocyte-to-monocyte ratio(LMR) in patients with hepatocellular carcinoma(HCC) undergoing curative hepatectomy.METHODS: Clinicopathological data of 210 hepatitis B virus(HBV)-associated HCC patients who were treated by radical hepatic resection between 2003 and 2010 were retrospectively analyzed. None of the patients received any preoperative anticancer therapyor intraoperative radiofrequency ablation. The diagnosis was confirmed by pathological examination after surgery. Absolute peripheral blood lymphocyte and monocyte counts were derived from serum complete blood cell count before surgery,and LMR was calculated by dividing lymphocyte count by monocyte count. The best cutoff was determined by receiver operating characteristics(ROC) curve analysis. Correlations between LMR levels and clinicopathological features were assessed using the χ2 test. Survival outcomes were estimated using the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate analyses were performed to evaluate the prognostic impact of LMR and other clinicopathological factors on overall survival(OS) and recurrence-free survival(RFS),using the Cox proportional hazards model.RESULTS: The optimal cutoff value of LMR for survival analysis was 3.23,which resulted in the most appropriate sensitivity of 55.3% and specificity of 74.7%,with the area under the curve(AUC) of 0.66(95%CI: 0.593-0.725). All patients were dichotomized into either a low(≤ 3.23) LMR group(n = 66) or a high(> 3.23) LMR group(n = 144). A low preoperative LMR level was significantly correlated with the presence of cirrhosis,elevated levels of total bilirubin and larger tumor size. Patients with a low LMR level had significantly reduced 5-year OS(61.9% vs 83.2%,P < 0.001) and RFS(27.8% vs 47.6%,P = 0.009) compared to those with a high LMR level. Multivariate analyses indicated that a lower LMR level was a significantly independent predictor of inferior OS(P = 0.003) and RFS(P = 0.006). Subgroup analysis indicated that survival outcome was significantly more favorable in cirrhotic patients with LMR > 3.23. However,there were no differences between low and high LMR groups for OS and RFS in non-cirrhotic patients.CONCLUSION: Preoperative LMR was demonstrated for the first time to serve as an independent prognostic factor in HBV-associated HCC patients after curative resection. Prospective studies with larger cohorts for validation are warranted.

Oncogenic ADAM28 induces gemcitabine resistance and predicts a poor prognosis in pancreatic cancer

BACKGROUND Pancreatic cancer is a major cause of cancer-related death,with a 5-year overall survival rate being below 5%.The main causes of poor prognosis in pancreatic cancer include easy metastasis,high recurrence rate,and robust drug resistance.Gemcitabine is a first-line drug for patients with unresectable pancreatic cancer.However,due to drug resistance,the clinical effect is not satisfactory.ADAM28 is reported as a tumor promoter in some cancers,but its role in pancreatic cancer and gemcitabine chemoresistance in pancreatic cancer has not been elucidated.AIM To identify if ADAM28 can act as an important target to reverse the gemcitabine drug resistance in pancreatic cancer.METHODS RNA-sequence analysis was applied to explore the potential targets involved in the gemcitabine of pancreatic cancer.SW1990 pancreatic cancer cells were treated with an increased dose of gemcitabine,and the mRNA levels of ADAM28 were evaluated by RT-PCR.The protein and mRNA levels of ADAM28 were confirmed in the gemcitabine resistant and parallel SW1990 cells.The ADAM28 expression was also assessed in TCGA and GEO databases,and the results were confirmed in the collected tumor and adjacent normal tissues.The overall survival(OS)rate and relapse-free survival(RFS)rate of pancreatic cancer patients with high ADAM28 level and low ADAM28 level in TCGA were evaluated with Kaplan-Meier Plotter.Furthermore,the OS rate was calculated in pancreatic cancer patients with high tumor mutation burden(TMB)and low TMB.CCK-8 assay was used to examine the effect of ADAM28 on the viability of SW1990 cells.The ADAM28 and its co-expressed genes were analyzed in the cBioPortal for cancer genomics and subjected to GSEA pathway analysis.The correlations of ADAM28 with GSTP1,ABCC1,GSTM4,and BCL2 were analyzed based on TCGA data on pancreatic cancer.RESULTS RNA-sequence analysis identified that ADAM28 was overexpressed in gemcitabine-resistant cells,and gemcitabine treatment could induce the expression of ADAM28.The mRNA and protein levels of ADAM28 were elevated in gemcitabine-resistant SW1990 cells compared with parallel cells.Also,the expression of ADAM28 was upregulated in pancreatic tumor tissues against normal pancreatic tissues.Notably,ADAM28 was highly expressed in the classical type than in the basal tumor type.Furthermore,the high expression of ADAM28 was associated with low OS and RFS rates.Interestingly,the high levels of ADAM28 was associated with a significantly lower OS rate in the high TMB patients,but not in the low TMB patients.Moreover,overexpression of ADAM28 could reduce the cell viability inhibition by gemcitabine,and knockdown of ADAM28 could enhance the proliferation inhibition by gemcitabine.The GSEA analysis showed that ADAM28 was related to the regulation of drug metabolism,and ADAM28 was significantly positively correlated with GSTP1,ABCC1,GSTM4,and BCL2.CONCLUSION This study demonstrates that ADAM28 is overexpressed in pancreatic cancer,and closely involved in the regulation of gemcitabine resistance.Overexpression of ADAM28 is a novel prognostic biomarker in pancreatic cancer.