Carrying G allele in rs786204926 involved in alternative splicing of PTEN is associated with chemosensitivity in breast cancer

Abstract

Background Chemoresistance is still the main reason for the failure of breast cancer treatment and is the main cause of death of breast cancer patients. Although many studies have shown the association between genetic polymorphisms of PTEN and chemoresistance, the molecular mechanism of breast cancer chemotherapy has not been further studied. This study aims to investigate the potential association between novel PTEN gene polymorphism and breast chemoresistance in Chinese population, and explore whether alternative splicing of the PTEN gene is affected by the gene polymorphism. Methods The study included 234 patients with breast cancer chemotherapy, 157 chemosensitive cases and 77 chemoresistant case. rs786204926, rs701848, rs12402181, rs35770269 were analysed using Sanger sequence and Sequenom MassArray typing technology. Silicon analysis was used to predict whether and how the polymorphism affects alternative splicing. Semi-quantitative RT-PCR and Western blot were further used to validate the silicon analysis. Results It is showed that there was a significant association between rs786204926 polymorphism and breast cancer chemoresistance. Carrying G allele or AG genotype will increase the risk of chemosensitivity in breast cancer. Additionally, Logistic multivariate regression analysis showed that age, lymph node metastasis and rs786204926 genotype are risk factors for breast cancer chemoresistance. Furthermore, Silico analysis showed that carrying G allele or AG genotype in chemosensitivity samples produced a new receptor site of alternative splicing, which increases the possibility of a new mutant PTEN isoform production. Interestingly, further experiments also verify this possibility. Conclusion We speculate that the mechanism of breast cancer chemosensitivity might be caused by a change in alternative splicing caused by the rs786204926 of PTEN gene. Thus, our study might provide theoretical guidance for the individualized treatment of clinical breast cancer patients.

Exploring the Potential of Stem Cell Therapy and Non-Opioid Anesthesia and Pain Reduction: Reducing the Negative Impact on the Individual and Society

“…For instance, lidocaine demonstrates efficacy as a neuroprotective agent, mitigating early postoperative cognitive dysfunction and neuropathic pain [5]. Comparative studies between opioid-free and opioid-based anesthesia reveal similar levels of pain reduction [35]. Non-opioid analgesics like acetaminophen and ketorolac prove effective in managing postoperative pain [36].…”

“…However, OFA may not suit all patients or surgical types, as it presents drawbacks. Also, limited investigation into intraoperative analgesia depth has been noted in some studies [35]. Nonetheless, employing non-opioid agents within OFA regimens can significantly enhance safety during the perioperative and postoperative periods.…”

“…Several limitations include the paucity of studies comparing the efficacy of intraoperative analgesia with non-opioid anesthesia (Table 2) [35]. Despite the availability of potent non-opioid analgesics with better side effect profiles and lower addiction risk, some contend that non-opioid strategies overlook gaps in evidence regarding their effectiveness [38].…”

“…Certain non-opioid analgesics, including lidocaine, ketamine, and gabapentinoids, have been linked to adverse effects such as sedation, drowsiness, and arrhythmia [39]. Opting out of opioids in the operating room may result in inadequate pain relief and increased rates of postoperative complications and hospital readmission [35,36]. Also, non-opioid anesthesia may careful patient selection, as it may not be suitable for all individuals.…”