Effect of surgery on the survival of elderly patients with early stage pancreatic cancer: A propensity‐matched analysis

Abstract Background and objectives Research about the effect of surgery in geriatric patients with early stage pancreatic ductal adenocarcinoma (PDAC) is limited, and it remains a subject of much debate. The purpose of this study was to evaluate the role of surgery on the survival of elderly patients with T1‐3N0M0 PDAC and to further investigate the prognosis of these patients undergoing different surgical methods. Methods Patients aged ≥65 with T1‐3N0M0 PDAC diagnosed in 2004–2016 were collected from the Surveillance, Epidemiology, and End Results database. The imbalance of baseline characteristics was reduced by propensity score matching. We used the log‐rank tests to evaluate overall survival (OS) and cancer‐specific survival (CSS) among different groups. Univariate and multivariate Cox regression analysis was utilized to explore prognostic factors in PDAC. Results In total, 6363 patients were enrolled. After matching, 1110 patients were paired. We found that surgery could provide better survival (p < 0.001). Moreover, compared with those who underwent partial resection or larger resection, patients who underwent local tumor destruction had poorer OS and CSS (p < 0.001). However, no statistically significant survival differences were shown between the partial resection group and the larger resection group (p < 0.001). Conclusion Surgical intervention could confer a survival benefit to elderly patients with early stage PDAC. Additionally, these patients could benefit from more radical operations, and radical operations with reasonable extents are advocated rather than too aggressive methods

Construction and validation of a hypoxia-related gene signature to predict the prognosis of breast cancer

Abstract Background Among the most common forms of cancer worldwide, breast cancer posed a serious threat to women. Recent research revealed a lack of oxygen, known as hypoxia, was crucial in forming breast cancer. This research aimed to create a robust signature with hypoxia-related genes to predict the prognosis of breast cancer patients. The function of hypoxia genes was further studied through cell line experiments. Materials and methods In the bioinformatic part, transcriptome and clinical information of breast cancer were obtained from The Cancer Genome Atlas(TCGA). Hypoxia-related genes were downloaded from the Genecards Platform. Differentially expressed hypoxia-related genes (DEHRGs) were identified. The TCGA filtered data was evenly split, ensuring a 1:1 distribution between the training and testing sets. Prognostic-related DEHRGs were identified through Cox regression. The signature was established through the training set. Then, it was validated using the test set and external validation set GSE131769 from Gene Expression Omnibus (GEO). The nomogram was created by incorporating the signature and clinicopathological characteristics. The predictive value of the nomogram was evaluated by C-index and receiver operating characteristiccurve. Immune microenvironment and mutation burden were also examined. In the experiment part, the function of the two most significant hypoxia-related genes were further explored by cell-line experiments. Results In the bioinformatic part, 141 up-regulated and 157 down-regulated DEHRGs were screened out. A prognostic signature was constructed containing nine hypoxia genes (ALOX15B, CA9, CD24, CHEK1, FOXM1, HOTAIR, KCNJ11, NEDD9, PSME2) in the training set. Low-risk patients exhibited a much more favorable prognosis than higher-risk ones (P < 0.001). The signature was double-validated in the test set and GSE131769 (P = 0.006 and P = 0.001). The nomogram showed excellent predictive value with 1-year OS AUC: 0.788, 3-year OS AUC: 0.783, and 5-year OS AUC: 0.817. Patients in the high-risk group had a higher tumor mutation burden when compared to the low-risk group. In the experiment part, the down-regulation of PSME2 inhibited cell growth ability and clone formation capability of breast cancer cells, while the down-regulation of KCNJ11 did not have any functions. Conclusion Based on 9 DEHRGs, a reliable signature was established through the bioinformatic method. It could accurately predict the prognosis of breast cancer patients. Cell line experiment indicated that PSME2 played a protective role. Summarily, we provided a new insight to predict the prognosis of breast cancer by hypoxia-related genes

Survival outcomes after breast-conserving therapy compared with mastectomy for patients with early-stage metaplastic breast cancer: a population-based study of 2412 patients

Background: Previous studies revealed that patients with early-stage metaplastic breast cancer (MBC) underwent mastectomy more often than breast-conserving therapy (BCT) mainly due to the larger tumor size. This study was performed to compare the survival outcomes following BCT versus mastectomy for patients with early-stage MBC. Methods: Surveillance, Epidemiology, and End Results (SEER) database was used to identify women diagnosed with early-stage MBC (T1-3N0-3M0) between 2001 and 2016, who were treated with either BCT or mastectomy. We assessed overall survival (OS) and breast cancer-specific survival (BCSS) using the Kaplan-Meier method and hazard ratios using Cox proportional hazards models. Results: A total of 2412 MBC patients were identified, 881 (36.5%) of whom underwent BCT and 1531(63.5%) underwent mastectomy. The median follow-up time was 73 months. Most of patients had older age (≥50 years old), larger tumor size, higher American Joint Committee on Cancer (AJCC) stage and hormone receptor negativity. After adjustment for confounding variables, patients who underwent BCT had significantly improved OS (5-year OS: 84.3% vs 62.5%; 10-year OS: 73.0% vs 52.1%; adjusted HR = 0.76, 95%CI: 0.59–0.97, p = 0.028) and BCSS (5-year BCSS: 89.1% vs 70.8%; 10-year BCSS: 83.9% vs 67.5%; adjusted HR = 0.72, 95%CI: 0.53–0.96, p = 0.026) than those who underwent mastectomy, and this improvement remained significant for all T and N stages of MBC except for N2-3 stage. Conclusion: BCT conferred improved OS and BCSS compared with mastectomy for patients with early-stage MBC, and the improvement persisted in almost all of the subgroups of different T and N stages