A Novel Cuproptosis-Related Prognostic Gene Signature and Validation of Differential Expression in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal cell carcinoma, which is characterized by metabolic reprogramming. Cuproptosis, a novel form of cell death, is highly linked to mitochondrial metabolism and mediated by protein lipoylation. However, the clinical impacts of cuproptosis-related genes (CRGs) in ccRCC largely remain unclear. In the current study, we systematically evaluated the genetic alterations of cuproptosis-related genes in ccRCC. Our results revealed that CDKN2A, DLAT, DLD, FDX1, GLS, PDHA1 and PDHB exhibited differential expression between ccRCC and normal tissues (|log2(fold change)| > 2/3 and p < 0.05). Utilizing an iterative sure independence screening (SIS) method, we separately constructed the prognostic signature of CRGs for predicting the overall survival (OS) and progression-free survival (PFS) in ccRCC patients. The prognostic score of CRGs yielded an area under the curve (AUC) of 0.658 and 0.682 for the prediction of 5-year OS and PFS, respectively. In the Kaplan−Meier survival analysis of OS, a higher risk score of cuproptosis-related gene signature was significantly correlated with worse overall survival (HR = 2.72 (2.01−3.68), log-rank p = 1.76 × 10−7). Patients with a higher risk had a significantly shorter PFS (HR = 2.83 (2.08−3.85), log-rank p = 3.66 × 10−7). Two independent validation datasets (GSE40435 (N = 101), GSE53757 (N = 72)) were collected for meta-analysis, suggesting that CDKN2A (log2(fold change) = 1.46, 95%CI: 1.75−2.35) showed significantly higher expression in ccRCC tissues while DLAT (log2(fold change) = −0.54, 95%CI: −0.93−−0.15) and FDX1 (log2(fold change) = −1.01, 95%CI: −1.61−−0.42) were lowly expressed. The expression of CDKN2A and FDX1 in ccRCC was also significantly associated with immune infiltration levels and programmed cell death protein 1 (PD-1) expression (CDKN2A: r = 0.24, p = 2.14 × 10−8; FDX1: r = −0.17, p = 1.37 × 10−4). In conclusion, the cuproptosis-related gene signature could serve as a potential prognostic predictor for ccRCC patients and may offer novel insights into the cancer treatment.

Effects of core needle biopsy and subsequent neoadjuvant chemotherapy on molecular alterations and outcome in breast cancer.

OBJECTIVES: The aim of our study is to evaluate the effect of core needle biopsy (CNB) and subsequent neoadjuvant chemotherapy (NAC) on the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth hormone receptor 2 (HER2) and Ki67 in breast cancer, and the associated influencing factors. MATERIALS AND METHODS: In this retrospective cohort study, 143 patients with primary operable breast cancer who received NAC were included. ER, PR, HER2 and Ki67 statuses were compared between pretreatment and posttreatment residual samples. A control group of paired core and excision tumors from 123 patients who did not receive NAC within the same study period was also assessed. Data on patients' clinicopathologic features were collected to identify associated influencing factors. RESULTS: Ki67 value significantly increased in excision tumors compared with paired core samples in controls without presurgery treatment (P<0.01), which was associated with the pathologic lymph node status and the interaction of PR and HER2 status (P=0.008 and 0.028, respectively). In 143 patients who underwent NAC, a significant decrease was observed in the expression of PR and Ki67 after NAC (P=0.003 and P<0.01, respectively). Further subgroup analysis showed that PR decrease was more obvious in premenopausal patients and Luminal A patients (P=0.006 and 0.002, respectively). CONCLUSION: Core samples could provide more reliable information on determination of molecular subtype than surgical excisions. Decreases in PR and Ki67 expression following NAC could be used as positive prognostic factors. We recommend repeat testing of these biologic markers following NAC for the sake of better disease management. To the best of our knowledge, this is the most comprehensive study to analyze the effect of neoadjuvant chemotherapy on molecular alteration and its associated influencing factors after reporting a CNB-associated Ki67 increase in the same study.

Approaches and genetic determinants in predicting response to neoadjuvant chemotherapy in locally advanced gastric cancer.

Gastric cancer remains a major health burden worldwide. There is near-universal agreement that neoadjuvant chemotherapy (NAC) is a preferred management for locally advanced gastric cancer (LAGC). However, the optimal approach for an individual patient is still not clear and remains controversial, which could be at least partly explained by the lack of predictive tools. The ability to predict chemosensitivity from NAC in routine clinical practice is difficult and is an area of intense investigation, especially in the Precision-Medicine Era. Available consistent evidence suggests that a favorable tumor histopathological response to NAC may be a useful positive prognostic marker in gastric cancer. Hence, it is reasonable to speculate that making the histopathological response from NAC predictable will dramatically facility the NAC and improve patients' outcome. This review provides an overview on the current status of predictive biomarkers for histopathological response from NAC in LAGC, including clinicopathological variables, imaging and molecular testing. Furthermore, limitations and future perspectives are also discussed.