ABSTRACT
PURPOSE: This study aimed to construct nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) for patients with locally advanced hypopharyngeal squamous cell carcinoma (HSCC). METHODS: 864 patients with locally advanced HSCC during 2010-2015 from the surveillance, epidemiology and end results (SEER) database were selected. After classifying continuous data by risk, Cox regression analyses were applied to detect significant independent prognostic factors, with which nomograms were established. To evaluate the value of nomograms, concordance index (C-index), area under the receiver-operating characteristic (ROC) curve (AUC), calibration curves, and decision curve analysis (DCA), Kaplan-Meier analysis was adopted. The efficacy of surgery in different risk groups was also studied to figure out people who can benefit from surgery. RESULTS: A total of 864 locally advanced HSCC patients were randomized into the training cohort (n = 608) and the validation cohort (n = 256). Age, race, tumor size, T stage, N stage, primary site, radiotherapy, and chemotherapy were independent prognostic factors for OS and CSS (except race) and formed the nomograms. The nomograms revealed satisfied performance in C-index, AUC, DCA, and calibration curves, and prevailed over American Joint Committee on Cancer (AJCC) TNM staging system in predicting OS and CSS. After risk stratification, patients of low-risk group resulted in the best outcomes. Patients in moderate-risk may benefit from surgery. CONCLUSIONS: Convenient and well-calibrated nomograms to predict OS and CSS for III/IVA/IVB-stage HSCC patients were set up and assessed and may do a favor to make clinical decisions.
Subject(s)
Head and Neck Neoplasms , Nomograms , Humans , Neoplasm Staging , Prognosis , SEER Program , Squamous Cell Carcinoma of Head and NeckABSTRACT
BACKGROUND: Radical or palliative surgery with subsequent adjuvant therapy is the routine treatment for stage II/III colorectal cancer(CRC) and some stage IV CRC patients. This study aimed to clarify the prognostic clinicopathological and genetic factors for these patients. METHODS: Fifty-five stage II-IV CRC patients undergoing surgery and adjuvant therapy were recruited, including patients without liver metastasis(5 at stage II, 21 at stage III) and with liver metastasis(29 at stage IV). Genetic alterations of the primary cancer tissues were investigated by whole exome sequencing(WES). Patients were followed up to 1652 days(median at 788 days). RESULTS: The mutational landscape of primary CRC tissue of patients with or without liver metastasis was largely similar, although the mutational frequency of TRIM77 and TCF7L2 was significantly higher in patients with liver metastasis. Several main driver gene co-mutations, such as TP53-APC, APC-KRAS, APC-FRG1, and exclusive mutations, such as TP53-CREBBP, were found in patients with liver metastasis, but not in patients without liver metastasis. No significant difference was found between the two groups in aberrant pathways. If stage II-IV patients were studied altogether, relapse status, SUPT20HL1 mutations, Amp27_21q22.3 and Del8_10q23.2 were independent risk factors(P<0.05). If patients were divided into two groups by metastatic status, surgery types and Amp6_20q13.33 were independent risk factors for patients without liver metastasis(P<0.05), while TRIM77 mutations were the only independent risk factor for patients with liver metastasis(P<0.05). CONCLUSIONS: Surgery types and Amp6_20q13.33 were independent risk factors for CRC patients without liver metastasis, and TRIM77 mutations were the independent risk factor for CRC patients with liver metastasis.
ABSTRACT
8bromo7methoxychrysin (BrMC), a novel chrysin analog, was reported to have anticancer activities. The aim of the present study was to investigate the molecular mechanism of 8bromo7methoxychrysin (BrMC)induced apoptosis via the Akt/forkhead box O3a (FOXO3a) pathway in cisplatin (DDP)sensitive and resistant ovarian cancer cells. The human ovarian cancer cell lines A2780 and A2780/DDP were cultured in vitro. Various molecular techniques were used to assess the expression of FOXO3a and B cell lymphoma 2 (Bcl2)interacting mediator of cell death (Bim) in cisplatinsensitive and resistant ovarian cancer cells. Different concentrations of BrMC induced apoptosis in cisplatinsensitive and resistant ovarian cancer cells. BrMCinduced apoptotic cell death occurred mainly by the activation of Akt, which was accompanied by the overexpression of transcription factor FOXO3a, with a concomitant increase in the expression levels of Bim. Silencing Bim expression by using small interfering RNA, attenuated the induction of apoptosis by BrMC treatment. The results indicated that BrMCinduced apoptosis in cisplatinsensitive and resistant ovarian cancer cells may occur via the regulation of Akt/FOXO3a, leading to Bim transcription.
