m6A-related lncRNA-based immune infiltration characteristic analysis and prognostic model for colonic adenocarcinoma.

BACKGROUND: Colonic adenocarcinoma (COAD) is a common gastrointestinal tract tumor, and its occurrence and progression are typically associated with genomic instability, tumor-suppressor gene and oncogene mutations, and tumor mutational load. N6-methyladenosine (m6A) modification of RNAs and long non-coding RNA (lncRNA) expression are important in tumorigenesis and progression. However, the regulatory roles of m6A-associated lncRNAs in the tumor microenvironment, stratification of prognosis, and immunotherapy are unclear. METHODS: We screened 43 prognostic lncRNAs linked to m6A and performed consistent molecular typing of COAD using consensus clustering. The single-sample Gene Set Enrichment Analysis and ESTIMATE algorithms were used to assess the immune characteristics of different subgroups. Covariation between methylation-related prognostic lncRNAs was eliminated by least absolute shrinkage and selection operator Cox regression. A nomogram was created and evaluated by combining the methylation-related prognostic lncRNA model with other clinical factors. The relationship between the prognostic model grouping and microsatellite instability, immunophenotype score, and tumor mutation burden was validated using R scripts. Finally, we used a linkage map to filter sensitive medicines to suppress the expression of high-risk genes. Three m6A-associated lncRNA modes were identified in 446 COAD specimens with different clinical endpoints and biological statuses. Risk scores were constructed based on the m6A-associated lncRNA signature genes. Patients with lower risk scores showed superior immunotherapy responses and clinical benefits compared to those with higher risk scores. Lower risk scores were also correlated with higher immunophenotype scores, tumor mutation burden, and mutation rates in significantly mutated genes (e.g., FAT4 and MUC16). Piperidolate, quinostatin, and mecamylamin were screened for their abilities to suppress the expression of high-risk genes in the model. CONCLUSIONS: Quantitative assessment of m6A-associated lncRNAs in single tumors can enhance the understanding of tumor microenvironment profiles. The prognostic model constructed using m6A-associated lncRNAs may facilitate prognosis and immunotherapy stratification of patients with COAD; finally, three drugs with potential therapeutic value were screened based on the model.

Cost-effectiveness analysis of pembrolizumab plus chemotherapy versus chemotherapy as the first-line treatment for advanced esophageal cancer.

OBJECTIVE: The KEYNOTE-590 trial showed that individuals with advanced esophageal cancer who received Pembrolizumab in combination with chemotherapy as a first-line regimen achieved a significant extension of survival. However, this treatment option increases the financial burden on patients and the economic benefits remain to be further evaluated. METHODS: A Markov model was used to simulate 10-year survival of patients with esophageal cancer from the perspective of United States (US) Medicare payers. We evaluated the economics of Pembrolizumab plus chemotherapy in the PD-L1 positive score (CPS ≥10) and any PD-L1 expression groups, respectively. We estimated total costs, quality-adjusted life years (QALYs), and calculated incremental cost effectiveness ratios (ICERs). Sensitivity analyses were conducted to explore the impact of uncertainties on the results. Subgroup analysis was also performed. RESULTS: The analysis results showed that the ICER for pembrolizumab plus chemotherapy versus chemotherapy alone was $293,513.17/QALYs in the any PD-L1 expression group. This exceeded the threshold of willingness to pay ($150,000/QALYs). ICERs were most sensitive to the cost of pembrolizumab and the ICERs exceeded $150,000/QALYs in all subgroups. CONCLUSIONS: Evidence suggests that first-line pembrolizumab in combination with chemotherapy is not a cost-effective option for advanced esophageal cancer in the US, regardless of PD-L1 expression status.

Chicken surimi fortified by omega-3 fatty acid addition: manufacturing and quality properties.

BACKGROUND: The meat of spent hens is hard to use owing to its small amount and poor quality. A washing process to remove sarcoplasmic proteins and other impurities can prolong the shelf life of surimi-like products. Owing to the benefits of omega-3 polyunsaturated fatty acids (ω-3 PUFAs), functional foods fortified with ω-3 PUFAs are increasingly being marketed. Hence, in this study, ω-3 FA-fortified chicken surimi was manufactured, and how to ameliorate its lipid peroxidation during frozen storage was investigated. RESULTS: A 0.10% (w/v) solution of sodium chloride (NaCl) instead of distilled water in the third washing step decreased (P < 0.05) myofibrillar protein loss and moisture content of spent hen breast protein recoveries. Oil droplets in fish, flaxseed or soybean oil-added chicken surimi were well distributed. Moreover, flaxseed oil addition increased (P < 0.05) total ω-3 FAs and ω-3/ω-6 FA ratio, while only fish oil provided long-chain PUFAs. Oil addition decreased (P < 0.05) hardness and gumminess of chicken surimi, while flaxseed oil resulted in more (P < 0.05) yellow surimi than fish and soybean oil. Fish oil-added samples showed higher (P < 0.05) lipid oxidation than flaxseed or soybean oil-added samples under -15 to -10 °C storage, but α-tocopherol addition ameliorated it. CONCLUSION: A novel semi-manufactured chicken surimi product with nutritional benefits could be developed by fortification with fish or flaxseed oil.