Frequency shift Raman-based sensing of serum MicroRNA for ultrasensitive cervical cancer diagnosis.

Cervical cancer is the most common gynaecological tumor. The development of a sensor for the ultrasensitive detection of cervical cancer is significant in guaranteeing its prognosis. Herein, we proposed a novel surface-enhanced Raman scattering (SERS) analysis platform using a frequency shifts-based sensing model for rapid and ultrasensitive microRNA (miRNA) assay. During the analysis process, miR-21 can be captured by the single-stranded DNA (ssDNA) modified on the platform which is complementary pairing with miR-21. The connection of miR-21 can lead to the variation of the molecular weight and result in the deformation extent of the Raman report molecule 6Thioguanine (6TG); thus, the peak at 1301 cm-1 due to the ring C-N stretches of 6TG shifts to lower frequency. The detection limit (LOD) of the proposed SERS analysis platform is as low as 8.32 aM. Moreover, the platform also has excellent specificity and repeatability, with the relative standard deviation (RSD) value of 6.53 %. Serum samples of cervical cancer patients and healthy subjects were analyzed via the platform and the accuracy of the detection results was verified by qRT-PCR, revealing that SERS results and qRT-PCR results have high homogeneity. Thus, the platform can serve as a potential tool for clinical diagnosis of cervical cancer.

A systematic review and meta-analysis of prognostic indicators in patients with head and neck malignancy treated with immune checkpoint inhibitors.

INTRODUCTION: Tumor immunotherapy has recently emerged as a crucial focal point in oncology treatment research. Among tumor immunotherapy approaches, tumor immune checkpoint inhibitors (ICIs) have attracted substantial attention in clinical research. However, this treatment modality has benefitted only a limited number of patients. We conducted a meta-analysis of various biomarkers to decipher their prognostic implications in patients with head and neck squamous cell carcinoma (HNSCC) who are treated with ICIs, and thus identify predictive markers with practical clinical relevance. METHODS: A systematic search of electronic databases was conducted to identify clinical studies that examined the correlation between biomarkers and treatment outcomes in the HNSCC patients. The included articles were screened and analyzed to extract data regarding overall survival (OS) and progression-free survival (PFS). RESULTS: The relationship between the biomarkers included in the summary and prognosis was as follows: HPV positivity was associated with improved OS (HR = 0.76, 95% CI = 0.58-1.99), PFS (HR = 1.16, 95% CI = 0.81-1.67), and response (OR = 1.67, 95% CI = 1.37-2.99). PD-L1 positivity was associated with OS (HR = 0.71, 95% CI = 0.59-0.85), PFS (HR = 0.56 95% CI = 0.43-0.73), and response (OR = 2.16, 95% CI = 1.51-3.10). Neither HPV positivity nor PD-L1 positivity was associated with DCR. The following markers were collected for OS and PFS data and were associated with longer OS: lower Glasgow prognostic score (GPS/mGPS) grading, lower PS grading, high body mass index (BMI), low neutrophil-to-lymphocyte ratio (NLR), low platelet-to-lymphocyte ratio (PLR), high albumin (Alb), low lactate dehydrogenase (LDH). Factors associated with better PFS were lower GPS/mGPS grading, lower PS grading, high BMI, low NLR, high absolute lymphocyte count, and low LDH. Hyperprogressive disease was associated with worse OS and PFS. Fewer clinical studies have been completed on the tumor microenvironment and hypoxia, microsatellite instability/DNA mismatch repair, and microbiome and systematic analysis is difficult. CONCLUSION: In our meta-analysis, different immune checkpoint factors were associated with different prognoses in HNSCC patients receiving immunotherapy. HPV, PD-L1, BMI, Alb, HPD, PS, GPS/mGPS, LDH, NLR, and PLR predicted the ICI outcome in HNSCC patients.

CSMVC: A Multiview Method for Multivariate Time-Series Clustering.

Multivariate time-series (MTS) clustering is a fundamental technique in data mining with a wide range of real-world applications. To date, though some approaches have been developed, they suffer from various drawbacks, such as high computational cost or loss of information. Most existing approaches are single-view methods without considering the benefits of mutual-support multiple views. Moreover, due to its data structure, MTS data cannot be handled well by most multiview clustering methods. Toward this end, we propose a consistent and specific non-negative matrix factorization-based multiview clustering (CSMVC) method for MTS clustering. The proposed method constructs a multilayer graph to represent the original MTS data and generates multiple views with a subspace technique. The obtained multiview data are processed through a novel non-negative matrix factorization (NMF) method, which can explore the view-consistent and view-specific information simultaneously. Furthermore, an alternating optimization scheme is proposed to solve the corresponding optimization problem. We conduct extensive experiments on 13 benchmark datasets and the results demonstrate the superiority of our proposed method against other state-of-the-art algorithms under a wide range of evaluation metrics.

Clinicopathological analysis of 67 cases of esophageal neuroendocrine carcinoma and the effect of postoperative adjuvant therapy on prognosis.

ABSTRACT: The clinicopathological properties of esophageal neuroendocrine carcinoma (ENEC) and its optimal therapy have not been widely studied, as the disease is not common. Consequently, we conducted a retrospective study to analyze the clinical features as well as the prognosis of patients with surgically resected ENEC.The clinicopathological data of patients with ENEC who underwent esophagostomy with regional lymphadenectomy at Jiangsu Province People's Hospital and Jiangsu Provincial Tumor Hospital starting January 2008 until December 2014 were collected.Ninety-two cases of ENEC were part of this study. However, only 67 patients were analyzed and followed up. A univariate model for the Cox proportional hazards revealed that prognosis was associated with postoperative adjuvant therapy, age, and lymph node metastasis (P < .05); a multivariate Cox proportional hazards model showed that postoperative adjuvant therapy was a significant independent prognostic factor. Postoperative adjuvant therapy directly affected overall survival, with a significant disparity noted between the groups (P = .022). In this study, patients who received adjuvant therapy had an average time of survival of 39 months (interquartile range: 27.068-50.932 months), while those who did not receive adjuvant therapy had an average survival time of 13 months (interquartile range: 10.129-15.871 months). The survival time was longer in the treated group than in the untreated group (hazard ratio = 0.47; 95% confidence interval: 0.23-0.94; P = .034).ENEC is a heterogeneous tumor with a very poor prognosis. Combining surgery with adjuvant and/or chemotherapy significantly prolongs the survival of patients, and the optimal treatment for ENEC should be determined with future prospective studies.

FTO promotes cell proliferation and migration in esophageal squamous cell carcinoma through up-regulation of MMP13.

FTO, a demethylase for N6-methyladenosine (m6A) modification, has been implicated in multiple tumors. However, its roles in esophageal squamous cell carcinoma (ESCC) remain uncovered. This study aims to evaluate the clinical relevance and functional roles in this disease. Through immunohistochemistry, qRT-PCR and Western blot analyses, we found FTO expression in ESCC tissues was stronger than that in adjacent normal tissues, and the survival curves displayed high FTO expression had a trend toward poor prognosis. Functionally, silencing of FTO inhibited ESCC cell growth and migration in CCK8, EdU, colony formation and transwell assays and FTO overexpression showed the opposite results. Furthermore, FTO was also required for the tumorigenicity of ESCC cells in nude mice. The data from RNA-seq analysis revealed that MMP13 expression was significantly affected by FTO knockdown. qRT-PCR and Western blot assays confirmed that MMP13 was positively regulated by FTO in both mRNA and protein levels. Additionally, the functional link between FTO and MMP13 was explored by CCK8 and transwell chamber approaches. These findings suggest that FTO is up-regulated and plays oncogenic roles in ESCC. MMP13 may function as a downstream target of FTO.

Gross tumor volume is an independent prognostic factor in patients with postoperative locoregional recurrence of esophageal squamous cell carcinoma.

Many cases of esophageal squamous cell carcinoma (ESCC) involve lymph node and distant metastases after esophagectomy, and most patients relapse within 2 years. Intensity-modulated radiotherapy (IMRT) is an important treatment for these cases of recurrence in ESCC and is widely used in clinical practice. A retrospective study of 137 postoperative patients with locoregional recurrences of ESCC who received IMRT was carried out. Kaplan-Meier survival curves and log-rank tests of univariate analysis was performed to assess whether there was a significant association between demographic and clinical features and death after recurrence. For multivariate analysis, the statistically significant results from the Kaplan-Meier method were subjected to Cox regression analysis. A total of 109 male and 28 female patients were included. There were 21 (15.3%), 58 (42.3%), 36 (26.3%), 3 (2.2%), 17 (12.4%), and 2 (1.5%) recurrences in the anastomotic, supraclavicular, mediastinal, tumor bed, polyregional, and abdominal regions, respectively. Univariate analysis showed that the gross tumor volume (GTV) of radiation (<27 vs. ≥27 cm3) and the number of lymph nodes were significantly associated with survival. The survival rates of patients at 1, 2, 3 and 5 years with GTV<27 cm3 were 72.7, 51.5, 37.1 and 25.9%, respectively, and with GTV≥27 cm3 were 63.7, 26.9, 17.9 and 0%, respectively. The significant independent prognostic factor was GTV [<27 vs. ≥27 cm3; hazard ratio (HR), 1.746; 95% confidence interval (CI), 1.112-2.741]. In conclusion, GTV of radiation (<27 vs. ≥27 cm3) is an independent factor in predicting locoregional recurrence after ESCC. Patients with GTV<27 cm3 are likely to have a better prognosis.

FOXO4 and FOXD3 are predictive of prognosis in gastric carcinoma patients.

Forkhead box (FOX) transcription factor family plays an important role in cancer growth and metastasis. This study aimed to determine the predictive ability of FOX genes in gastric carcinoma. A total of 360 patients with gastric from The Cancer Genome Atlas (TCGA) cohorts were collected in this study. The expression profile of FOX family were obtained from the TCGA RNAseq database. Clinicopathological characteristics, including age, gender, tumor node metastasis (TNM), tumor grade, and overall survival were collected. Univariate and multivariate Cox proportional hazards model were used to assess the risk factors for survival, and the results were further validated in in-house cohort. In the TCGA cohort, FOXO4 (HR = 0.613, 95%CI 0.452-0.832) and FOXD3 (HR = 1.704, 95%CI 1.212-2.397) were shown independently predictive of overall survival in gastric cancer after Cox proportional hazards analysis. The finding was validated in our in-house cohort, which demonstrated that both FOXO4 and FOXD3 were independent predictors for overall survival (FOXO4 high, HR: 0.445, 95%CI 0.277-0.715, P = 0.001, FOXD3 high, HR: 1.927, 95%CI 1.212-3.063, P = 0.006) and disease free survival (FOXO4 high, HR: 0.628, 95%CI 0.420-0.935, P = 0.022, FOXD3 high, HR: 1.698, 95%CI 1.136-2.540, P = 0.010).Collectively, FOX family paly critical roles in gastric cancer, and FOXO4 and FOXD3 were identified as independent prognostic factors for survival outcomes of gastric cancer. Further functional study is needed to understand more about FOX family in gastric cancer.