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Abstract Previous studies have shown a relationship between SPECC1 and the prognosis of breast cancer, indicating a potential function for SPECC1 in the initiation and progression of cancer. However, the role played by SPECC1 in other tumors is not yet known. Therefore, we used bioinformatics techniques to conduct a thorough investigation into the possible mechanism of SPECC1 in pan-cancer, analyzing data reported in the literature as well as databases such as GTEx and CCLE, cBioportal, TCGA, and UCSC XENA. Comparing the results with matching normal tissues, the majority of cancers, including pancreatic adenocarcinoma (PAAD) and breast invasive carcinoma (BRCA), exhibited higher levels of SPECC1, while hepatocellular carcinoma (HCC) showed lower expression levels. SPECC1 was also found to be genetically mutated in endometrial cancer, sarcoma, and esophageal cancer. The prognosis of lung adenocarcinoma, kidney papillary cell carcinoma, and breast cancer is highly correlated with dysregulation of SPECC1 expression. This work helps guide clinical therapy by highlighting the sensitivity of tumor-treating medicines and the prognostic importance of SPECC1 in various malignancies. KEGG pathway enrichment analysis revealed focused adhesion, collagen-containing extracellular matrix (collagen), and the primary enrichment domains for SPECC1-related genes. These findings were obtained through gene annotation (GO) examination of SPECC1 expression. Primary mediators of the cytokine-cytokine receptor interaction include PICOC1-associated genes, cell-substrate junction genes, and extracellular matrix containing collagen. PICOC1-associated genes primarily mediate the PI3K-AKT signaling pathway. Drug sensitivity assay showed that SPECC1 high-expressing cell lines were more sensitive to docetaxel, doxorubicin, etc. In conclusion, the current study shows how SPECC1 is expressed in different cancers and how this expression relates to the prognosis of the tumor. It also revealed the mutations and copy number variations of SPECC1 in various tumors and its potential involvement in cellular pathway regulatory networks and cytological processes. This study examines the relationship between immune genes, cellular infiltration, and immunological scores in the tumor microenvironment, which explain the severity of the disease. This study looks at the response of SPEC1 expression to anticancer therapy. Explains the prognostic significance and drug response of SPECC-1.

Background: Endoscopic nipple-sparing mastectomy (E-NSM) is a promising procedure in the treatment of breast cancer, but the limitations of endoscopic tools and intrinsic technical complexity of the technique hinder its applicability. Here, we introduce a novel surgery, gasless endoscopic transaxillary subcutaneous mastectomy and immediate reconstruction with implants (GETSMIRI), for breast cancer. and early effects. Methods: A retrospective analysis of the clinical data of 11 female patients, aged 50 (27–78) years, admitted to our hospital from January to December 2022, who underwent gasless endoscopic transaxillary subcutaneous mastectomy and immediate reconstruction with implants (GETSMIRI), was conducted. This study was designed to assess patient satisfaction before and after breast reconstruction, early complications, and breast function. Results: The tumors were all solitary, with a mean maximum diameter of 1.0 (0–2.0) cm and a mean distance of 2.3 (2–4) cm from the nipple, the mean intraoperative bleeding volume was 47.5 mL, and the mean hospital stay was 1.5 d. Postoperatively, 1 patient developed depigmentation of the nipple due to mild ischemia. There were no incisional complications, subcutaneous emphysema, infection, areola necrosis, skin flap necrosis, or removal of the prosthesis and/or patch. No tumor recurrence or metastasis was observed during the follow-up period. The difference between breast satisfaction and psychosocial health scores was not statistically significant (P = 0.680; P = 0.612). Conclusion: GETSMIRI, immediate implantable breast reconstruction, is less invasive than other such procedures, and short-term follow-up results show good postoperative satisfaction, making it an alternative surgical method.

Background Triple-negative breast cancer (TNBC) is a highly aggressive type of cancer with few available treatment methods. The aim of the current study was to provide a prognostic autophagy-related gene (ARG) model to predict the outcomes for TNBC patients using bioinformatic analysis. Methods mRNA expression data and its clinical information for TNBC samples obtained from The Cancer Genome Atlas (TCGA) and Metabric databases were extracted for bioinformatic analysis. Differentially expressed autophagy genes were identified using the Wilcoxon rank sum test in R software. ARGs were downloaded from the Human Autophagy Database. The Kaplan–Meier plotter was employed to determine the prognostic significance of the ARGs. The sample splitting method and Cox regression analysis were employed to establish the risk model and to demonstrate the association between the ARGs and the survival duration. The corresponding ARG-transcription factor interaction network was visualized using the Cytoscape software. Results A signature-based risk score model was established for eight genes (ITGA3, HSPA8, CTSD, ATG12, CLN3, ATG7, MAP1LC3C, and WIPI1) using the TCGA data and the model was validated with the GSE38959 and Metabric datasets, respectively. Patients with high risk scores had worse survival outcomes than those with low risk scores. Of note, amplification of ATG12 and reduction of WIPI were confirmed to be significantly correlated with the clinical stage of TNBC. Conclusion An eight-gene autophagic signature model was developed in this study to predict the survival risk for TNBC. The genes identified in the study may favor the design of target agents for autophagy control in advanced TNBC.

Introduction: Breast cancer (BC) and thyroid dysfunction are common in females, yet the relationship between thyroid hormone and BC is unclear. To search for the connection between thyrotropin and BC, we contradistinguished BC patients with or without synchronous second primary thyroid cancer (TC) with surgery using data from the Surveillance, Epidemiology, and End Results (SEER) database. Theoretically, according to the ATA (American Thyroid Association) guidelines, all TC patients were treated with thyrotropin suppressive therapy only from 2010 to 2015. Materials and Methods: Data from BC patients with a synchronous second TC with surgery (BC2TC) and only BC patients (1BC) during 2010–2015 were extracted from the SEER database. Differences in the clinicopathological characteristics between BC2TC and 1BC patients were analyzed by chi-square tests. Comparisons of the disease-specific survival (DSS) and overall survival (OS) curves between these two groups were performed with the log-rank (Mantel-Cox) test. Results: Within this dataset, we identified 134 BC2TC patients during the period from 2010 to 2015. Significant differences between the BC2TC and 1BC groups were found only for different ages and TNM (tumor-node-metastasis status) stages. There were no significant differences in DSS between the two cohorts (P = 0.060). The same tendencies in OS or DSS were observed for the different age groups and different TNM groups, even the stage I, N0 (without metastases to lymph nodes), and ER (+) (estrogen receptor (ER)-positive) groups. Conclusions: There were no remarkable differences in survival between the BC2TC and 1BC groups, and thyrotropin suppression therapy using levothyroxine did not negatively affect BC prognosis.

Objective: Recently, performing locoregional surgical treatment still remains debatable in patients with metastatic breast cancer (MBC). Current study aimed to develop prognostic nomograms for predicting the long-term survival in MBC patients with or without surgical intervention, thereby assisting clinicians in making individualized choice.Methods: The training set included 5173 patients who were diagnosed with MBC in 2010–2013 from the Surveillance, Epidemiology, and End Results Program, while the validation set comprised 2924 patients diagnosed in 2014–2015. Multivariant Cox hazard model was applied to determine the independent risk factors for overall survival (OS) and breast cancer specific survival (BCSS). Then, individualized pre- and postoperative nomograms for predicting 1- or 3-year survival probabilities were constructed accordingly. Internal and external validations were conducted to determine the accuracy of these nomograms by calculating concordance index (C-index) and plotting calibration curves.Results: The survival analysis indicated that surgical management conferred improved OS and BCSS in patients with metastatic breast cancer. Age, T stage, grade, distant metastatic site, ER, PR and HER2 status, radiation, and chemotherapy were independent risk factors for OS and BCSS both in surgery and non-surgery group. All these factors were subsequently incorporated into the nomogram which showed acceptable predictive capabilities with C-index range of 0.65–0.80 both in training set and external validation set. In addition, a preoperative nomogram incorporating variables capable of being determined before surgery was also built with C-index above 0.70 both in training and validation set.Conclusion: Surgical management in patients with metastatic breast cancer suggests a potential survival advantage. In addition, these well-validated pre- and postoperative nomograms may provide a useful tool to assist clinicians in treatment decision-making and in evaluating patients' long term prognosis.

Abstract Background Heat shock protein 90 (HSP90) functions as a well-known onco-protein to regulate protein conformation, stability and degradation. Pyruvate kinase M2 (PKM2), a critical regulator of the metabolism, growth and metastasis of cancer cells, has been confirmed to be overexpressed in various human cancer including hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying the oncogenic functions of HSP90 and PKM2 overexpression in HCC remain unknown. Methods The expression of HSP90 and PKM2 in HCC specimens and cells were detected by immunoblotting and immunostaining. The interaction between HSP90 and PKM2 was confirmed by tandem affinity purification, co-immunoprecipitation and Glutathione S transferase (GST)-pulldown assay. Results In this study, we found that HSP90 could bind to PKM2 and subsequently increased PKM2 abundance in HCC cells. Immunohistochemistry (IHC) staining showed that HSP90 level was positively correlated with PKM2 level in HCC tissues. Mechanistically, HSP90 was found to increase the phosphorylation of PKM2 at Thr-328. Protein kinase glycogen synthase kinase-3β (GSK-3β) formed a protein complex with HSP90 and PKM2, and directly mediated Thr-328 phosphorylation of PKM2 induced by HSP90. Thr-328 phosphorylation was critical for maintaining PKM2 stability and its biological functions in regulating glycolysis, mitochondria respiration, proliferation and apoptosis. Functionally, we found that HSP90 promoted the glycolysis and proliferation and inhibited apoptosis of HCC cells in a PKM2 dependent manner. In vivo experiments disclosed that PKM2 was required for the promoting effects of HSP90 on the growth of HCC cells in mice. Furthermore, we demonstrated that positive expression of HSP90 and PKM2 was correlated with poor clinicopathological features including high alpha fetoprotein (AFP) level, large tumor size, portal vein tumor thrombus (PVTT) and advanced tumor-node-metastasis (TNM) stage. Furthermore, we demonstrated that positive expression of HSP90 and PKM2, and a combination of these proteins could strongly predict the poor prognosis of HCC patients. Conclusions We suggest that HSP90 potentiates the glycolysis and proliferation, reduces the apoptosis and thus enhances the growth of HCC cells through PKM2.

Breast cancer (BC) and thyroid cancer (TC) are common malignancies among females. However, the connection between TC and BC is not well understood. To explore the relationship between these two cancers and to determine the effect of second metachronous TC on BC survival, we compared BC patients with or without second primary TC using data from the Surveillance, Epidemiology, and End Results (SEER) database. We extracted data from patients with only BC or TC and from BC patients with a second metachronous cancer from 2000-2014. Differences in the clinicopathological and treatment characteristics between BC patients with or without second metachronous TC were analyzed by chi-square tests. Multivariate analyses of BC survival were performed by using Cox regression models. Comparison of disease-specific survival (DSS) curves between these cohorts was performed with the log-rank (Mantel-Cox) test. Survival analyses were also performed using data from 1980-1994. Within this dataset, we found 1,262 BC cases in which a second metachronous TC (BC2TC) developed, accounting for 3.1% of all metachronous cancers following BC from 2000-2014. No significant differences were found in molecular markers. In addition, the mean age at BC diagnosis was younger in the BC2TC group than in the BC group (55.418 y vs 60.273 y). Half of the BC2TC patients developed TC in the first three years following BC diagnosis. Patients with BC2TC showed better DSS than those with BC alone from 2000-2014 (P