Development and validation of autophagy-related-gene biomarker and nomogram for predicting the survival of cutaneous melanoma.
- 作者列表："Wan Q","Jin L","Su Y","Liu Y","Li C","Wang Z
:Autophagy plays a critical role in cutaneous melanoma, but the prognostic research of differentially expressed autophagy-related genes (DEARGs) in melanoma is lacking. Therefore, autophagy-related gene expression data of 630 melanoma patients were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas database. The DEARGs were identified by "limma" package in R software. Best survival analysis and the least absolute shrinkage and selection operator method were performed to identify a robust 7-DEARG signature as well as construct nomogram associated with the clinical characteristics and validation in internal and external sets. This 7-DEARG signature could be regarded as an independent prognostic signature in clinical setting, and nomogram may supply a more simple and accurate prediction for the prognosis of melanoma. Moreover, 5 cancer hallmarks and 18 potential compounds are commonly enriched in high-risk expression phenotype. Thus, our finding provides new clinical evidences for the accurate diagnosis and identifies a potential prognostic autophagy-related marker for the treatment of melanoma.
: 自噬在皮肤黑色素瘤中起关键作用，但缺乏黑色素瘤中差异表达自噬相关基因 (DEARGs) 的预后研究。因此，从 gene expression Omnibus (GEO) 和癌症基因组图谱数据库中获得了 630 例黑色素瘤患者的自噬相关基因表达数据。DEARGs 由 R 软件中的 “limma” 包识别。进行最佳生存分析和最小绝对收缩和选择算子方法，以确定稳健的 7-DEARG 签名，并构建与临床特征相关的列线图，并在内部和外部集进行验证。该 7-DEARG 标记可被视为临床环境中的独立预后标记，列线图可能为黑色素瘤的预后提供更简单和准确的预测。此外，5 种癌症标志和 18 种潜在化合物通常富集在高风险表达表型中。因此，我们的发现为准确诊断提供了新的临床证据，并确定了治疗黑色素瘤的潜在预后自噬相关标志物。
METHODS::In colorectal cancer (CRC), hepatic arterial infusion (HAI) chemotherapy may convert primarily unresectable CRC liver metastases (CLM) into resectability, although the risk of metastatic recurrence remains high after CLM ablation. We investigated the role of antitumour immunity invoked by first-line oxaliplatin-HAI for long-term CLM outcome. In a prospective study cohort of primarily unresectable CLM, we assessed patients' fms-related tyrosine kinase 3 ligand (FLT3LG) in serum, reflecting opportune intratumoural immune activity, at baseline and following 1-3 sequences of oxaliplatin-HAI. The end points were CLM resectability and overall survival. Patients who presented an immediate twofold increment of circulating FLT3LG during the treatment and at its completion were scored as CLM resectable (16.4% with both features), were alive at final follow-up 8-12 years later. All patients experienced FLT3LG increase during the treatment course, but those who remained unresectable or had the disease converted but presented a slow and gradual FLT3LG accretion, later died of the metastatic disease. These data provide further support to our previous findings that tumour-directed immunity invoked by oxaliplatin-containing therapy predicts excellent outcome of early advanced CRC if macroscopic tumour ablation is rendered possible by the 'classic' tumour response to the cytotoxic treatment.
METHODS::Prostate cancer is one of the primary causes of death around the world. As an important drug, flutamide has been used in the clinical diagnosis of prostate cancer. However, the over dosage and improper discharge of flutamide could affect the living organism. Thus, it necessary to develop the sensor for detection of flutamide with highly sensitivity. In this paper, we report the synthesis of lanthanum cobaltite decorated halloysite nanotube (LCO/HNT) nanocomposite prepared by a facile method and evaluated for selective reduction of flutamide. The as-prepared LCO/HNT nanocomposite shows the best catalytic performance towards detection of flutamide, when compared to other bare and modified electrodes. The good electrochemical performance of the LCO/HNT nanocomposite modified electrode is ascribed to abundant active sites, large specific surface area and their synergetic effects. Furthermore, the LCO/HNT modified electrode exhibits low detection limit (0.002 μM), wide working range (0.009-145 μM) and excellent selectivity with remarkable stability. Meaningfully, the developed electrochemical sensor was applied in real environmental samples with an acceptable recovery range.
METHODS::Several studies have indicated that cancer-associated fibroblasts (CAFs) could promote cancer progression in many malignancies. However, the mechanism by which CAFs promote the growth and metastasis of lung cancer remains poorly defined. In the present study, CAFs and normal fibroblasts (NFs) were isolated from human lung cancer and adjacent tissue. The data showed that the conditional medium (CM) of CAFs could increase the proliferation, migration and invasion of lung cancer cells. Vascular cell adhesion molecule-1 (VCAM-1) showed a higher expression in CAF-CM than NF-CM, and blocking VCAM-1 in CAF-CM attenuated the proliferation and invasion of cancer cells. Further, the results showed that VCAM-1 secreted from CAFs activated AKT and MAPK signaling via receptor α4β1 integrin (very-late antigen (VLA)-4) in lung cancer cells. Moreover, CAFs promoted VCAM-1 expression and tumor growth in vivo. Additionally, bioinformatics analysis indicated a positive correlation on the CAF marker protein alpha-smooth muscle actin (α-SMA) and VCAM-1 expression, which was associated with a poor prognosis in lung cancer patients. These findings demonstrate that the VCAM-1 secreted from CAFs enhances growth and invasion by activating the AKT and MAPK signaling of lung cancer cells.