Whole-Exome Sequencing and Experimental Validation Unveil the Roles of TMEM229A Q200del Mutation in Lung Adenocarcinoma.

INTRODUCTION: Lung adenocarcinoma (LUAD) is one of the major histopathological types of non-small cell lung cancer (NSCLC), including solid, acinar, lepidic, papillary and micropapillary subtypes. Increasing evidence has shown that micropapillary LUAD is positively associated with a higher percentage of driver gene mutations, a higher incidence of metastasis and a poorer prognosis, while lepidic LUAD has a relatively better prognosis. However, the novel genetic change and its underlying mechanism in the progression of micropapillary LUAD have not been exactly determined. METHODS: A total of 181 patients with LUAD who underwent surgery at the First Affiliated Hospital of Huzhou University from January 2020 to December 2022 were enrolled. Three predominant lepidic and three predominant micropapillary LUAD tissue samples were carried out using whole-exome sequencing. Comprehensive analysis of genomic variations and the difference between lepidic and micropapillary LUAD was performed. In addition, the TMEM229A Q200del mutation was verified using our cohort and TCGA-LUAD datasets. The correlations between the TMEM229A Q200del mutation and the clinicopathological characteristics of patients with LUAD were further analyzed. The functions and mechanisms of TMEM229A Q200del on NSCLC cell proliferation and migration were also determined. RESULTS: The frequency of genomic changes in patients with micropapillary LUAD was higher than that in patients with lepidic LUAD. Mutations in EGFR, ATXN2, C14orf180, MUC12, NOTCH1, and PKD1L2 were concomitantly detected in three predominant micropapillary and three predominant lepidic LUAD cases. The TMEM229A Q200del mutation was only mutated in lepidic LUAD. Additionally, the TMEM229A Q200del mutation had occurred in 16 (8.8%) patients, and not found TMEM229A R76H and M346T mutations in our cohort, while TMEM229A mutations (R76H, M346T, and Q200del) occurred only in 1.0% of the TCGA-LUAD cohort. Further correlation analysis between the TMEM229A Q200del mutation and clinicopathological characteristics suggested that a lower frequency of the Q200del mutation was significantly associated with positive lymph node metastasis, advanced TNM stage, positive cancer thrombus, and pathological features. Finally, overexpression of TMEM229A Q200del suppressed NSCLC cell proliferation and migration in vitro. Mechanistically, overexpression of TMEM229A and TMEM229A Q200del both reduced the expression level of phosphorylated (p)-ERK and p-AKT (Ser473), and the reduced protein level of p-ERK in the TMEM229A Q200del group was more pronounced compared to the TMEM229A group. CONCLUSION: Our results demonstrated that the TMEM229A Q200del mutant may play a protective role in the progression of LUAD via inactivating ERK pathway, providing a potential therapeutic target in LUAD.

Early Enteral Nutrition Versus Parenteral Nutrition After Resection of Esophageal Cancer: a Retrospective Analysis.

This study aimed to compare the clinical outcomes and hospitalization cost between early enteral nutrition (EEN) and parenteral nutrition (PN) after resection of esophageal cancer. A total of 79 patients with esophageal cancer who underwent surgical treatment in our hospital from July 2010 to July 2013 were enrolled in this study. They were divided into EEN group (n = 39) and PN group (n = 40) based on the nutrition support modes. The clinical factors such as time to first fecal passage, postoperative albumin infusion, differences of serum albumin value, hospital stay, systematic inflammatory response syndrome (SIRS) duration, complications, initial hospitalization cost, and mortality were retrospectively compared. The EEN group had a significantly shorter hospital stay, lower initial hospitalization cost, earlier first fecal passage, and shorter duration of SIRS than PN group (P < 0.05). The dose of albumin infusion was significantly smaller in EEN group (P < 0.05) and the decreased value of serum albumin (Δalb) was more prominent in PN group compared with EEN group (P < 0.05). The percentage of patients having any postoperative complication was much higher in PN group than EEN group (P < 0.05), but there was no significant difference in in-hospital morbidity between two groups. Pneumonia was found significantly more frequent in PN group compared with EEN group (P < 0.05). Early EN started within 48 h after esophagectomy is safe, economic, and superior for reduction of postoperative complication, for promoting early recovery of intestinal movement, and for early recovery from systemic inflammation.

Clinical observation of docetaxel or gemcitabine combined with cisplatin in the chemotherapy after surgery for stage II-III non-small cell lung cancer.

AIM OF THE STUDY: This study aimed to compare the efficacy and toxicity of docetaxel combined with cisplatin (DP) and gemcitabine combined with cisplatin (GP) in postoperative chemotherapy after surgery of non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: A total of 92 patients diagnosed with NSCLC after surgery were enrolled, and they were treated with DP (DP group) and GP (GP group). The efficacy and toxicity of the medications were then compared. RESULTS: Approximately 92.4% (85 out of 92) of the patients received chemotherapy for more than three weeks. In the DP and GP groups, the incidence rates of grade III-IV thrombocytopenia were 24.4% and 6.38%, respectively, whereas the incidence rates of alopecia were 88.9% and 25.5%, respectively. The difference between the two groups was statistically significant (p < 0.05). Disease-free survival rates in DP group in one and two years were 76.5% and 50.47%, respectively, whereas in the GP group they were 77.8% and 49.52%, respectively. No significant difference was observed between the two groups (p > 0.05). CONCLUSIONS: These results showed similar disease-free survival rates of DP and GP therapies in one and two years after surgery for NSCLC. However, the DP group exhibited higher incidence rates of grade III-IV thrombocytopenia and alopecia than the GP group. Therefore, we should select a specific treatment for each patient according to individual differences.