METTL3-modified lncRNA DSCAM-AS1 promotes breast cancer progression through inhibiting ferroptosis.

Numerous studies have indicated that N6-methyladenosine (m6A) and lncRNAs play pivotal roles in human cancer. However, the underlying functions and mechanisms of m6A-lncRNA in the physiological processes of breast cancer remain unclear. Here, we found that DSCAM-AS1 is an m6A-modified lncRNA that was overexpressed in breast cancer tissues and cells, indicating poor clinical prognosis. Gain/loss functional assays suggested that DSCAM-AS1 inhibited erastin-induced ferroptosis in breast cancer cells. Mechanistically, there were remarkable m6A modification sites on both the 3'-UTR of DSCAM-AS1 and the endogenous antioxidant factor SLC7A11. M6A methyltransferase methyltransferase-like 3 (METTL3) methylated both SLC7A11 and DSCAM-AS1. Moreover, DSCAM-AS1 recognized m6A sites on the SLC7A11 mRNA, thereby enhancing its stability. Taken together, these findings indicated a potential therapeutic strategy for breast cancer ferroptosis in an m6A-dependent manner.

The crosstalk between metabolic reprogramming and epithelial-mesenchymal transition and their synergistic roles in distant metastasis in breast cancer.

BACKGROUND: Metabolic reprogramming (MR) and epithelial-mesenchymal transition (EMT) are crucial phenomena involved in the distant metastasis of breast cancer (BRCA). This study aims to assess the risk of distant metastasis in BRCA patients based on MR and EMT processes and investigate their underlying mechanisms. METHODS: Gene sets related to EMT and MR were downloaded. MR-related genes (MRG) and EMT-related genes (ERG) were obtained. Principal Component Analysis method was used to define the EMT Potential Index (EPI) and MR Potential Index (MPI) to quantify the EMT and MR levels in each tumor tissue. A linear scoring model, the Metastasis Score, was derived using the union of MRGs and ERGs to evaluate the risk of distant metastasis/recurrence in BRCA. The Metastasis Score was then validated in multiple datasets. Additionally, our study explored the underlying mechanism of the Metastasis Score and its association with tumor immunity, focusing on HPRT1 gene expression in breast cancer tissues of transfer and untransferred groups using experimental methods. RESULTS: A total of 59 MRGs and 30 ERGs were identified in the present study. Stratifying the dataset based on EPI and MPI revealed significantly lower survival rates (P < .05) in the MPI_high and EPI_high groups. Kaplan-Meier analysis indicated the lowest survival rate in the EPI-high + MPI-high group. The Metastasis Score demonstrated its ability to distinguish prognoses in GSE2034, GSE17705, and TCGA-BRCA datasets. Additionally, differences in mutated genes were found between the high- and the low-Metastasis Score groups, displaying significant associations with immune cell infiltration and anti-tumor immune status. Notably, the 13 genes included in the Metastasis Score showed a strong association with prognosis and tumor immunity. Immunohistochemistry and western blot results revealed high expression of the HPRT1 gene in the transfer group. CONCLUSION: This study established the Metastasis Score as a reliable tool for evaluating the risk of distant metastasis/recurrence in BRCA patients. Additionally, we identified key genes involved in MR and EMT crosstalk, offering valuable insights into their roles in tumor immunity and other relevant aspects.

Prediction of Lymphovascular invasion status in breast cancer based on magnetic resonance imaging radiomics features.

OBJECTIVE: This study intended to investigate the feasibility and effectiveness of using clinical magnetic resonance imaging (MRI) radiomics features to predict lymphovascular invasion (LVI) status in breast cancer (BC) patients. METHODS: A total of 182 BC patients were retrospectively collected and randomly divided into a training set (n = 127) and a validation set (n = 55) in a 7:3 ratio. Based on pathological examination results, the training set was further divided into LVI group (n = 60) and non-LVI group (n = 67), and the validation set was divided into LVI group (n = 24) and non-LVI group (n = 31). General data and MRI examination indicators were compared. Multivariate logistic regression was utilized to analyze MRI radiomics features and clinically relevant indicators that were significant in the baseline information of patients in training set, independent risk factors were identified, and a logistic regression model was built. The accuracy of logistic model was validated using ROC curves in training and validation sets. RESULTS: Age, pathohistological classification, tumor length, tumor width, presence or absence of Magnetic Resonance Spectroscopy (MRS) cho peak, presence or absence of spicule sign, peritumoral enhancement, and peritumoral edema were statistically significant (P < 0.05) between the two groups. Multivariate logistic regression analysis presented that spicule and peritumoral edema were independent risk factors for LVI in BC patients (P < 0.05). The ROC curve illustrated that AUC of the logistic regression model in the training set was 0.807 (95%CI: 0.730-0.885) and that in the validation set was 0.837 (95%CI: 0.731-0.944). CONCLUSION: Radiomics features of spicule sign and peritumoral edema were independent risk factors for LVI in BC patients. A logistic regression model based on these factors, along with age, could accurately predict LVI occurrence in BC patients, providing data support for diagnosis and modeling of LVI in BC patients.

Application of a modified lateral thoracic artery perforator flap in partial breast defects.

Background: Breast cancer has become the most frequently diagnosed cancer in the world. Detection at an early stage, frequently allows women to benefit from breast conserving surgery. However, some patients are not satisfied with the breast shape after breast-conserving surgery, and autologous tissue flaps are needed to fill the defect in the resection area. The modified lateral thoracic artery perforator (LTAP) flap isn't one of the commonly used flaps in breast surgery and has the advantages of a reliable blood supply, simple operation and few postoperative complications. In this study, we aimed to evaluate the feasibility and effectiveness of a modified LTAP flap for repairing partial breast defects after breast-conserving surgery. Methods: In this study, we retrospectively analyzed the clinical data of 126 patients treated with LTAP flaps to repair local breast defects at Affiliated Hospital of Guangdong Medical University between January 2020 and June 2021. Data were collected on the demographic characteristics of these patients, tumor size and location, type of axillary lymph node surgery, availability of adjuvant chemotherapy and radiotherapy, and postoperative complications. Results: The median weight of the tumor specimen was 185 g (range, 170-320 g), and this glandular tissue accounted for 30% to 40% of the total breast volume. The average flap size was 10.5 cm ×2.5 cm (length range, 8-15 cm, width range: 2-4 cm). The minimum follow-up time was 6 months, with an average of 10 months (range, 6-22 months). The mean operative time was 130 minutes (range: 90-180 minutes), and the mean hospital stay was 3 days (range, 2-5 days). All modified LTAP flaps survived completely without donor site complications. None of the patients required revision surgery on the postoperative breast. Conclusions: The modified LTAP flap is a reliable method for repairing partial breast defects after breast-conserving surgery. It has the advantages of a simple operation, a reliable blood supply, fewer postoperative complications, and a high flap survival rate. It is especially suitable for Asian women with small breast volumes and can achieve good breast contouring effects.

In vitro study of piwi interaction RNA-31106 promoting breast carcinogenesis by regulating METTL3-mediated m6A RNA methylation.

Background: Breast cancer is the most common gynecological malignancy and the leading cause of cancer-related deaths in women. P-element induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are novel non-coding RNAs whose abnormal expressions have been closely associated with multiple cancers. This study explored the roles and possible mechanisms of piRNA-31106 in breast cancer. Methods: The expression of piRNA-31106 in breast cancer tissues and cells was detected by reverse transcription polymerase chain reaction (RT-PCR). The pcDNA vector containing piRNA-31106 (pcDNA-piRNA-31106) and a short hairpin (sh)RNA containing piRNA-31106 (shRNA-piRNA-31106) were used to interfere with piRNA-31106 expression in breast cancer cells. The effects on cell proliferation, apoptosis/cell cycle, invasion, and metastasis were detected via Cell Counting Kit-8 (CCK-8), flow cytometry, transwell assays, and scratch tests, respectively. The protein expressions of murine double minute 2 (MDM2), cyclin-dependent kinase 4 (CDK4), and cyclinD1 were detected by Western blot analysis. The N6-methyladenosine (m6A) RNA methylation level and the binding relationship between piRNA-31106 and METTL3 were analyzed. The role of METTL3 in the regulation of breast cancer by piRNA-31106 was further analyzed by using small interfering (si)RNA targeting METTL3. Results: PiRNA-31106 was highly expressed in breast cancer tissues and cell lines MDA-MB-231 and MCF-7. Overexpression of piRNA-31106 promoted the viability, invasion, and migration of breast cancer, inhibited apoptosis, and promoted the expressions of MDM2, CDK4, and cyclinD1. Inhibition of piRNA-31106 showed the opposite effect. In addition, piRNA-31106 promoted the m6A methylation levels and facilitated methyltransferase-like 3 (METTL3) expression in MDA-MB-231 and MCF-7 cells. RNA immunoprecipitation (RIP) assays confirmed the binding relationship between piRNA-31106 and METTL3. Further experiments demonstrated that si-METTL3 could inhibit the regulatory effects of piRNA-31106 on breast cancer. Conclusions: PiRNA-31106 was significantly highly expressed in breast cancer and could promote breast cancer progression by regulating METTL3-mediated m6A RNA methylation.

Reconstruction of complex chest wall defects: A case report.

BACKGROUND: Chronic radiative chest wall ulcers are common in patients undergoing radiation therapy. If not treated early, then symptoms such as erosion, bleeding and infection will appear on the skin. In severe cases, ulcers invade the ribs and pleura, presenting a mortality risk. Small ulcers can be repaired with pedicle flaps. Because radioactive ulcers often invade the thorax, surgeons need to remove large areas of skin and muscle, and sometimes ribs. Repairing large chest wall defects are a challenge for surgeons. CASE SUMMARY: A 74-year-old female patient was admitted to our department with chest wall skin ulceration after radiation therapy for left breast cancer. The patient was diagnosed with chronic radioactive ulceration. After multidisciplinary discussion, the authors performed expansive resection of the chest wall ulcers and repaired large chest wall defects using a deep inferior epigastric perforator (DIEP) flap combined with a high-density polyethylene (HDPE) patch. The patient was followed-up 6 mo after the operation. No pigmentation or edema was found in the flap. CONCLUSION: DIEP flap plus HDPE patch is one of the better treatments for radiation-induced chest wall ulcers.

Strategies for the selection of oncoplastic techniques in the treatment of early-stage breast cancer patients.

BACKGROUND: In recent years, breast cancer is the most common malignancy in women. The traditional method of surgery is to remove a woman's breast completely, which has a negative impact on her work and life. Today, women have a fiery pursuit to maintain their perfect figure, which has forced breast surgeon to find a new surgical approach to maintain the shape of the breast after surgery. METHODS: This study systematically analyzed and summarized the incision design and repair of glandular defects in early-stage breast cancer patients by oncoplastic breast techniques. By summarizing the methods of oncoplastic breast surgery (OBS) in different quadrants, it could help beginners to master this technology more quickly, so as to provide better help for breast cancer patients. RESULTS: A total of 216 breast cancer patients who underwent OBS from January 2016 to June 2020 at the Affiliated Hospital of Guangdong Medical University were included in this study. In patients treated with the volume-displacement method and the volume-replacement method, 92.6% and 86.2% of patients achieved excellent breast shape, respectively. CONCLUSIONS: OBS is a safe and effective way to treat early-stage breast cancer while obtaining better breast shape, reducing postoperative psychological trauma, and improving quality of life.

Modified radical mastectomy for anterior thoracic nerve and intercostobrachial nerve protection (case report).

Modified breast cancer radical mastectomy is a more common operating method in breast surgery. Traditional modified radical mastectomy focuses on protecting the long thoracic nerve and thoracodorsal nerve while ignoring the protection of the anterior thoracic nerve and intercostobrachial nerve protection, which leads often to patients with upper medial arm numbness, acid swelling, pain, chest atrophy, and other problems. In the modified radical mastectomy of breast cancer, in this case, the author used an elaborative operation to protect the anterior thoracic nerve and intercostobrachial nerve and thoroughly dissected the third-level lymph nodes through the axillary approach.

Reconstruction of the chest wall in locally advanced breast cancer with multi-disciplinary cooperation: a case report of mesh repair plus TRAM combined with DIEP chest wall reconstruction.

Locally advanced breast cancer, which is defined as a malignant breast tumor that invades or adheres to the surrounding tissue, is characterized by the invasion of the chest wall and the skin surface by the tumor. Multiple lymph nodes are invaded and fuse into a mass, causing extensive axillary lymph node metastasis. However, locally advanced breast cancer does not exhibit distant metastasis. At present, in most hospitals in China and the rest of the world, this type of breast cancer is primarily managed through systematic and local treatments. However, a consensus concerning the optimal surgical method for chest wall reconstruction, which for many surgeons is a difficult and confusing procedure, has not been reached. In the past, many breast centers had used skin flap combined with hard mesh titanium alloy plate to repair the large chest wall defects. Although titanium alloy plate can maintain the stability of the chest wall, it may have a negative effect on the follow-up radiotherapy of breast cancer patients, which is a controversial method. In addition, titanium alloy mesh also has the risk of deformation and fracture. These factors will cause some hidden dangers to patient safety. According to the research, the soft mesh not only has the characteristics of satisfactory compatibility and robustness for maintaining the stability of chest wall, but also does not affect the postoperative radiotherapy of patients. Combined with the advantages of soft mesh, Our department treated a case of locally advanced breast cancer with chest wall invasion. Through cooperation between the breast surgery and thoracic surgery departments, a mesh repair plus transverse rectus abdominis myocutaneous (TRAM) combined with deep inferior epigastric perforator (DIEP) procedure was performed to remove the breast tumor and repair the large area of skin defect after surgery, and a relatively satisfactory therapeutic effect was achieved. In this case, we took two novel approaches: first, a 4-layer high-density polyethylene mesh was used to repair the defect; secondly, the inferior epigastric artery perforation was anastomosed with the thoracoacromial artery (end-to-end anastomosis) and the inferior epigastric vein perforation was anastomosed with the axillary vein (end-to-side anastomosis).