Prognostic model of ER-positive, HER2-negative breast cancer predicted by clinically relevant indicators

Purpose To study the clinicopathological variables connected with disease-free survival (DFS) as well as overall survival (OS) in patients who are ER-positive or HER2-negative and to propose nomograms for predicting individual risk. Methods In this investigation, we examined 585 (development cohort) and 291 (external validation) ER-positive, HER2-negative breast cancer patients from January 2010 to January 2014. From January 2010 to December 2014, we retrospectively reviewed and analyzed 291 (external validation) and 585 (development cohort) HER2-negative, ER-positive breast cancer patients. Cox regression analysis, both multivariate and univariate, confirmed the independence indicators for OS and DFS. Results Using cox regression analysis, both multivariate and univariate, the following variables were combined to predict the DFS of development cohort: pathological stage (HR = 1.391; 95% CI = 1.043–1.855; P value = 0.025), luminal parting (HR = 1.836; 95% CI = 1.142–2.952; P value = .012), and clinical stage (HR = 1.879; 95% CI = 1.102–3.203; P value = 0.021). Endocrine therapy (HR = 3.655; 95% CI = 1.084–12.324; P value = 0.037) and clinical stage (HR = 6.792; 95% CI = 1.672–28.345; P value = 0.009) were chosen as predictors of OS. Furthermore, we generated RS-OS and RS-DFS. According to the findings of Kaplan–Meier curves, patients who are classified as having a low risk have considerably longer DFS and OS durations than patients who are classified as having a high risk. Conclusion To generate nomograms that predicted DFS and OS, independent predictors of DFS in ER-positive/HER2-negative breast cancer patients were chosen. The nomograms successfully stratified patients into prognostic categories and worked well in both internal validation and external validation (AU)

Prognostic model of ER-positive, HER2-negative breast cancer predicted by clinically relevant indicators.

PURPOSE: To study the clinicopathological variables connected with disease-free survival (DFS) as well as overall survival (OS) in patients who are ER-positive or HER2-negative and to propose nomograms for predicting individual risk. METHODS: In this investigation, we examined 585 (development cohort) and 291 (external validation) ER-positive, HER2-negative breast cancer patients from January 2010 to January 2014. From January 2010 to December 2014, we retrospectively reviewed and analyzed 291 (external validation) and 585 (development cohort) HER2-negative, ER-positive breast cancer patients. Cox regression analysis, both multivariate and univariate, confirmed the independence indicators for OS and DFS. RESULTS: Using cox regression analysis, both multivariate and univariate, the following variables were combined to predict the DFS of development cohort: pathological stage (HR = 1.391; 95% CI = 1.043-1.855; P value = 0.025), luminal parting (HR = 1.836; 95% CI = 1.142-2.952; P value = .012), and clinical stage (HR = 1.879; 95% CI = 1.102-3.203; P value = 0.021). Endocrine therapy (HR = 3.655; 95% CI = 1.084-12.324; P value = 0.037) and clinical stage (HR = 6.792; 95% CI = 1.672-28.345; P value = 0.009) were chosen as predictors of OS. Furthermore, we generated RS-OS and RS-DFS. According to the findings of Kaplan-Meier curves, patients who are classified as having a low risk have considerably longer DFS and OS durations than patients who are classified as having a high risk. CONCLUSION: To generate nomograms that predicted DFS and OS, independent predictors of DFS in ER-positive/HER2-negative breast cancer patients were chosen. The nomograms successfully stratified patients into prognostic categories and worked well in both internal validation and external validation.

Pan-Cancer Analysis of Prognostic and Immune Infiltrates for the TMEM65, Especially for the Breast Cancer.

Introduction: Transmembrane protein 65 (TMEM65) is an inner mitochondrial membrane protein, which played important role in mediating autophagy, smooth muscle contraction, protein glycosylation, and immune response. In recent years, the interest had risen for exploring the function of the TMEM genes in the cancer fields. As a consequence, in our pan-cancer research of the TMEM65, we explored the function of the gene in kinds of database and tried to apply the finding in the clinical practice. Methods: In this research, we provide a comprehensive investigation of TMEM65 expression in a pan-cancer manner containing 33 cancer types. We evaluated the association of TMEM65 with the prognosis, immune infiltration, drug sensitivity analysis, GSVA enrichment analysis, TMB, MSI, NEO, and hotspot mechanisms. Results: TMEM65 was abnormally expressed in 24 types of cancers and showed correlation with the OS for 6 cancers and PFI for 9 cancers and kpI for 3 types. Moreover, the TME score, CD8 T effector, and immune checkpoint scoring systems showed a close correlation with the TMEM65. Moreover, TMEM65 was strongly correlated with some of the most common tumor-related genes and certain pathways (TGF beta signaling, TNFA signaling, hypoxia, pyroptosis, DNA repairing, autophagy, ferroptosis, and other related genes). Additionally, the TMEM65 showed correlations with the tumor mutational burden (TMB), microsatellite instability (MSI), NEO, and drug sensitivity. Finally, we confirmed several pathways by the GSEA and GSVA for the TMEM65 at the breast cancer aspects. Nomogram prediction model was also established for the breast tumors based on the TMEM65 level and other variables. Conclusion: Above all, the TMEM65 played important roles in predicting the prognosis of the cancers and correlated with the tumor immunity in the pan-cancer analysis.

Erratum: Effects of Galectin-1 on Biological Behavior in Cervical Cancer: Erratum.

[This corrects the article DOI: 10.7150/jca.38538.].

Overexpression of galectin2 (LGALS2) predicts a better prognosis in human breast cancer.

BACKGROUND: Galectins (LGALS) are a family of carbohydrate-binding proteins, and LGALS family members have shown prognostic roles in various types of cancers. However, the prognostic significance of some LGALS family members has not been studied in breast malignancy. METHODS: The prognostic value of LGALS family mRNA expression in breast cancer patients was investigated according to distinct clinicopathological features (including lymph node, intrinsic subtype, pathological grade, HER2, and TP53 status) using the Kaplan-Meier plotter database. Quantitative real-time polymerase chain reaction and western blotting were used to detect the mRNA and protein expression of LGALS in breast cancer and normal breast cells. The aberrant expression of specific LGALS and its correlation with breast cancer outcomes remains elusive. In the present analysis, we comprehensively explored an immunohistochemistry-based map of protein expression profiles in normal tissues, cancer, and cell lines from the widely available Human Protein Atlas (HPA) database. Immunohistochemistry was applied to evaluate the expression of LGALS between cancer and normal tissues. RESULTS: Our results showed that overexpression of LGALS2 mRNA were correlated with satisfactory overall survival among all breast cancer patients. Furthermore, LGALS2 and LGALS4 expression correlated with a better overall survival (OS) in grade III breast cancer patients; LGALS2 also predicted a better OS in basal-like subtype patients, luminal B patients, HER2-overexpressing patients, TP53 mutated and wild breast cancer patients. Notably, the mRNA and protein expression levels of LGALS2 were decreased in cancer cells compared with normal cells (P<0.05). Furthermore, LGALS2 expression in immunostaining score was lower in cancer tissues than in normal tissues (P<0.005). CONCLUSION: In conclusion, LGALS2 has potential as a valuable biomarker for envisaging a satisfactory prognosis in patients with breast tumours, particularly those with luminal and basal B types, all stages and grade III tumours.

Prognostic role of overexpressed Bromodomain and extra-terminal family in ovarian cancer.

Background: BET family proteins have a role as epigenetic readers to accelerate the transcription of target genes. Several studies have shown that the BET protein family played important roles in several biological processes. Although, the prognostic influence of individual BET genes family in ovarian cancer patients remains unclear. Methods: We investigated BET mRNA prognostic roles subtypes in ovarian cancer patients by means of the KM plotter database. The BET mRNA expression and protein in cancer and normal ovarian cells was determined using qRTPCR and western blot. We used the HPA database to look at the protein expression profiles in normal and cancer tissues for this study. Results: Among BET members, mRNA expression BRD2 showed improve OS in all the ovarian malignancy patients, serous patients, stage III and IV, grade II and grade III, TP53 mutated ovarian cancer patients, as well as all patients treated with Platin based chemotherapy. As for BRD3, we found that BRD3 expression was related to better OS in endometrioid ovarian carcinoma and stage III+IV ovarian carcinoma patients, as well as all patients managed with Taxol and concurrent Taxol+Platin based chemotherapy. In addition, BRDT was associated with better OS in all ovarian carcinoma patients, grade I and grade III, all clinical stage (I+II, III+IV) patients, as well as all patients cured with Taxol and concurrent Taxol+Platin chemotherapy. Conclusion: We conclude that high expression of BRD2, BRD3, and BRDT predicted a better prognosis. mRNA expression of BET family is considerably associated with the prognosis of ovarian carcinoma and individual BET family gene could act as a predictive prognostic indicator in ovarian carcinoma.

Overexpression of Galectin10 Predicts a Better Prognosis in Human Ovarian Cancer.

To explore the prognosis of Galectins (LGALS) expression on patients with ovarian cancer, the prognosis of LGALS members in ovarian cancer was retrieved and analyzed by using 'Kaplan-Meier plotter' database. The relation of LGALS to overall survival (OS) was evaluated according to histological subtypes, clinical stages and pathological grade. Quantitative real-time polymerase chain reaction and western blot were used to detect the mRNA and protein expression of LGALS in ovarian cancer and normal ovarian cells. Immunohistochemistry was applied to evaluate the different expression of LGALS between cancer and normal tissues. In total patients with ovarian cancer, LGALS4, LGALS8, LGALS10 and LGALS13 mRNA levels were related to a better OS, and LGALS1 to a worse OS. LGALS1 predicted a worse OS in women with serous, stages III+IV or grade II ovarian cancer. LGALS4 predicted a better OS in patients with endometrioid, stages I+II or grade III ovarian cancer. LGALS10 predicted a longer OS in females with serous, all stages, or grade III cancer. LGALS8 overexpression was related to a better OS in all stages. Notably, mRNA and protein expressions of LGALS4, LGALS10 and LGALS13 were decreased in cancer cells than those in normal cells (P<0.05). Additionally, the immunostaining score of LGALS8, LGALS10 and LGALS13 expression were lower but LGALS1 was higher in caner tissues than those in normal tissues (P<0.001). In conclusion, LGALS10 possibly is a valuable biomarker for predicting a favorable prognosis in patients with ovarian cancer, especially with serous, all stages and grade III cancer.

Effects of Galectin-1 on Biological Behavior in Cervical Cancer.

Background: We previously revealed that the expression of galectin-1 (LGALS1) was significantly reduced after neoadjuvant chemotherapy treatment in cervical cancer patients. The objective of this study is to investigate the effects of LGALS1 expression on biological behaviors of cervical cancer cells. Methods: Immunohistochemistry and immunocytochemistry were performed to detect the expression of LGALS1 in cervical cancer tissues and cells (SiHa and C33A). Western blot analysis was performed to evaluate the efficacy of lentivirus-mediated upregulation or downregulation of LGALS1 in cervical cancer cells. Cell viability and proliferation were detected by CCK-8 and BrdU assays, respectively. Annexin V-FITC/PI apoptosis detection kit was employed to measure the apoptosis of cervical cancer cells. Transwell invasion and migration assays were also conducted to explore the invasive and migratory capabilities of cervical cancer cells. The expression of apoptosis- (Bcl-2 and Bax), invasion- (MMP-2 and MMP-9), and migration-related (Fascin and Ezrin) proteins, were detected by Western blot analysis. Xenograft mouse model of cervical cancer was generated to explore whether LGALS1 overexpression could promote tumor growth in vivo. Results: LGALS1 was overexpressed in cervical cancer tissues and cell lines compared to that in normal cervical tissues and epithelium cells. Upregulation of LGALS1 significantly promoted the cell proliferation, inhibited cell apoptosis, and enhanced the migratory and invasive abilities of both SiHa and C33A cells, whereas downregulation of LGALS1 led to the opposite results. The level of Bcl-2, MMP-2, MMP-9, Fascin, and Erzin expression was significantly upregulated in cervical cancer cells with LGALS1 overexpression, while converse results were obtained in LGALS1 knockdown cancer cells. In vivo study also showed that LGALS1 overexpression facilitated tumor growth of cervical cancer cells. Conclusion: Overexpression of LGALS1 significantly promoted and enhanced the aggressive features of cervical cancer both in vitro and in vivo, which may be associated with high expression of Bcl-2, MMP-2, MMP-9, Fascin, and Erzin proteins.

The Role of Galectins in Tumor Progression, Treatment and Prognosis of Gynecological Cancers.

Galectins are the member of soluble proteins that bind with ß-galactoside containing glycans. These proteins have been considered to be associated in various important events such as different types of cancers. It has been found that galectins could contribute to neoplastic transformation or regulate cell growth, cell apoptosis, and immune cells, causing tumor invasion, progression, metastasis and angiogenesis. Somehow, galectins are also found to exert a protective effect on cancer in a tissue-dependent way. These glycans binding proteins have been shown to be involved in the regulation of different tumor suppressor genes and oncogenes with their possible roles in human cancers. Objective of the current review is to summarize the role of galectin-1, -3 -7, and -9 in tumorigenesis of gynecological cancers. Galectin protein may be a potential therapeutic target in gynecological malignancies due to reported radio- and chemo- sensitivities, immunotherapeutic, anti-angiogenic and anti-proliferative activities. This review considers the evidence for the future research that how galectins may be important in the progression and treatment of gynecological cancers along with its potent use as a novel prognostic marker.

Significance of aquaporins' expression in the prognosis of gastric cancer.

Gastric carcinoma is one of the most lethal malignancy at present with leading cause of cancer-related deaths worldwide. Aquaporins (AQPs) are a family of small, integral membrane proteins, which have been evidenced to play a crucial role in cell migration and proliferation of different cancer cells including gastric cancers. However, the aberrant expression of specific AQPs and its correlation to detect predictive and prognostic significance in gastric cancer remains elusive. In the present study, we comprehensively explored immunohistochemistry based map of protein expression profiles in normal tissues, cancer and cell lines from publicly available Human Protein Atlas (HPA) database. Moreover, to improve our understanding of general gastric biology and guide to find novel predictive prognostic gastric cancer biomarker, we also retrieved 'The Kaplan-Meier plotter' (KM plotter) online database with specific AQPs mRNA to overall survival (OS) in different clinicopathological features. We revealed that ubiquitous expression of AQPs protein can be effective tools to generate gastric cancer biomarker. Furthermore, high level AQP3, AQP9, and AQP11 mRNA expression were correlated with better OS in all gastric patients, whereas AQP0, AQP1, AQP4, AQP5, AQP6, AQP8, and AQP10 mRNA expression were associated with poor OS. With regard to the clinicopathological features including Laurens classification, clinical stage, human epidermal growth factor receptor 2 (HER2) status, and different treatment strategy, we could illustrate significant role of individual AQP mRNA expression in the prognosis of gastric cancer patients. Thus, our results indicated that AQP's protein and mRNA expression in gastric cancer patients provide effective role to predict prognosis and act as an essential agent to therapeutic strategy.

Prognostic values of aquaporins mRNA expression in human ovarian cancer.

Aquaporins (AQPs), a family of transmembrane channel, are composed of 13 identified members (AQP0-12). Accumulating evidences reported that AQPs were correlated with various biological roles and represented a prognostic predictor in various cancer types. However, the prognostic value of AQPs expression in ovarian cancer remains unclear. Using 'Kaplan-Meier plotter' (KM plotter) online database, we explored the predictive prognostic value of individual AQPs members' mRNA expression to overall survival (OS) in different clinical data, such as histology, pathological grades, clinical stages, TP53 status, and applied chemotherapy in ovarian cancer patients. Our results revealed that higher AQP0, AQP1, and AQP4 mRNA expression were correlated with poor OS, whereas higher AQP3, AQP5, AQP6, AQP8, AQP10, and AQP11 showed better OS in ovarian cancer patients. Moreover, AQP4 and AQP8 showed poor OS in TP53-mutated ovarian cancer patients and AQP1 presented unfavorable OS in both TP53 mutated and wild ovarian cancer patients. Additionally, AQP3, AQP6, and AQP11 mRNA expression were correlated with better OS, whereas AQP0 and AQP1 showed poor OS in all ovarian cancer patients treated with Platin, Taxol, and Taxol + Platin chemotherapy. AQP5, AQP8, and AQP10 were associated with improved OS, however, AQP4 predicted unfavorable OS in all patients treated with Platin chemotherapy. Our results suggest that individual AQPs, except AQP2 and AQP9, are associated with unique prognostic significance and may thus act as new predictive prognostic indicators and potential drug therapeutic target in ovarian cancer.

Effect of micronutrient supplementation on IVF outcomes: a systematic review of the literature.

There is accumulating evidence on the importance of micronutrients in improving fertility in couples undergoing IVF therapy. Despite this, studies reporting the relevant clinical outcomes of IVF, such as pregnancy and live birth rates, are very scarce. This review aimed to systematically summarize clinical evidence on the effect of micronutrients on primary outcome parameters of IVF treatment. The literature was searched up to February 2017 through Embase and PubMed databases for relevant studies. The quality of eligible studies was assessed with the Downs and Black checklist. A total of five studies qualified for inclusion. These studies reported outcomes on 467 participants administered micronutrient supplements alone or combined with other nutrients as part of IVF therapy. There was significant heterogeneity among the interventions and study designs. However, all the studies reported a positive impact of micronutrient supplementation on clinical outcomes of IVF therapy in terms of pregnancy rate and/or live birth rate. Within the limits of this review, micronutrients appear to influence positive outcomes in couples undergoing fertility treatment. Larger clinical studies are needed to strengthen these findings so that the benefit of micronutrients can be extended to subjects undergoing IVF therapy.

Predictive role of galectin-1 and integrin α5ß1 in cisplatin-based neoadjuvant chemotherapy of bulky squamous cervical cancer.

Although galectin-1 and integrin α5ß1 confer chemoresistance to certain types of cancer, whether their expression predicts the response to cisplatin-based neoadjuvant chemotherapy (NACT) in squamous cervical cancer remains unclear. Paired tumor samples (pre- and post-chemotherapy) were obtained from 35 bulky squamous cervical cancer patients treated with cisplatin-based NACT and radical hysterectomy at our hospital between January 2007 and August 2014. The expression of galectin-1 and integrin α5ß1 in tumor cells and stromal cells was analyzed by immunohistochemistry. The correlation between galectin-1/integrin α5ß1 and apoptosis-associated markers was investigated by using the The Cancer Genome Atlas (TCGA) RNA-sequencing data. Seventeen patients were identified as chemotherapy responders and 18 as non-responders. Galectin-1 and integrin α5ß1-positive immunostaining was more frequently observed in stromal cells than its in tumor cells. The expression of galectin-1 and integrin α5ß1 in stromal and tumor cells was significantly down-regulated in postchemotherapy cervical cancer tissues. High levels of galectin-1 and integrin α5ß1 in stromal were associated with a negative chemotherapy response in squamous cervical cancer patients treated with cisplatin-based NACT. Additionally, the expression of galectin-1 and integrin α5 correlated negatively with caspase 3/caspase 8 by using the TCGA RNA-sequencing data. Galectin-1 and integrin α5ß1 expression in stromal may serve as a prediction of the responses to cisplatin-based NACT for patients with bulky squamous cervical cancer. Galectin-1 and integrin α5ß1 may be implicated in the development of chemoresistance in cervical cancer via suppressing apoptosis.