Added value of systemic inflammation markers for monitoring response to neoadjuvant chemotherapy in breast cancer patients.

BACKGROUND: Complete response after neoadjuvant chemotherapy (rNACT) elevates the surgical outcomes of patients with breast cancer, however, non-rNACT have a higher risk of death and recurrence. AIM: To establish novel machine learning (ML)-based predictive models for predicting probability of rNACT in breast cancer patients who intends to receive NACT. METHODS: A retrospective analysis of 487 breast cancer patients who underwent mastectomy or breast-conserving surgery and axillary lymph node dissection following neoadjuvant chemotherapy at the Hubei Cancer Hospital between January 1, 2013, and October 1, 2021. The study cohort was divided into internal training and testing datasets in a 70:30 ratio for further analysis. A total of twenty-four variables were included to develop predictive models for rNACT by multiple ML-based algorithms. A feature selection approach was used to identify optimal predictive factors. These models were evaluated by the receiver operating characteristic (ROC) curve for predictive performance. RESULTS: Analysis identified several significant differences between the rNACT and non-rNACT groups, including total cholesterol, low-density lipoprotein, neutrophil-to-lymphocyte ratio, body mass index, platelet count, albumin-to-globulin ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio. The areas under the curve of the six models ranged from 0.81 to 0.96. Some ML-based models performed better than models using conventional statistical methods in both ROC curves. The support vector machine (SVM) model with twelve variables introduced was identified as the best predictive model. CONCLUSION: By incorporating pretreatment serum lipids and serum inflammation markers, it is feasible to develop ML-based models for the preoperative prediction of rNACT and therefore facilitate the choice of treatment, particularly the SVM, which can improve the prediction of rNACT in patients with breast cancer.

[Corrigendum] Rab22a is a novel prognostic marker for cell progression in breast cancer.

Following the publication of this article, the authors have realized that Table I contained an error: The number of patients who were alive in the Rab22a high expression group should have been written as 77 instead of 772.
A corrected version of the Table is shown on the next page (the corrected datum is highlighted in bold). The authors sincerely apologize for the error that was introduced during the preparation of this Table, and regret any inconvenience that this mistake has caused. [the original article was published in International Journal of Molecular Medicine 45: 1037-1046, 2020; DOI: 10.3892/ijmm.2020.4486].

Rab22a is a novel prognostic marker for cell progression in breast cancer.

Breast cancer (BC) is the most common female malignant tumor worldwide. The mechanism of tumorigenesis is still unclear. Ras­related proteins in brain (Rab)22a belongs to the Ras superfamily, which may act as an oncogene and participate in carcinogenesis. The present study aims to identify whether Rab22a could be a novel biomarker of prognosis and determine the effects of Rab22a on BC cell progression. A total 258 BC and 56 para­tumor or non­tumor formalin fixed paraffin embedded tissues were stained through immunohistochemistry. The association between Rab22a expression and clinicopathological features, as well as overall survival status were analyzed. The expression level of Rab22a in breast cell lines were detected using reverse transcription­quantitative PCR and western blotting. SK­BR­3 cells were infected with Rab22a short hairpin RNA lenti­virus and the ability of cell proliferation, migration and invasion were measured. Gene Set Enrichment Analysis (GSEA) was employed to analyze the pathways involved in the Rab22a mRNA high level group. Rab22a was found to be overexpressed in BC tissues and upregulated in BC cells. High expression of Rab22a was related to a poor prognosis of patients with BC. Knockdown of Rab22a decreased the proliferation, migration and invasion ability of BC cells. GSEA indicated that certain pathways, including mammalian target of rapamycin complex 1 and protein secretion were upregulated, while pathways, such as hypoxia and KRas were downregulated in the Rab22a high level group. Rab22a is of prognostic value for BC and necessary for BC cell proliferation.

Risk factors of breast intraductal lesions in patients without pathological nipple discharge.

The majority of breast cancer arises from the ductal epithelium. It is crucial in the diagnosis and treatment of breast cancer by detecting intraductal lesions at an early stage. The typical clinical characteristic of intraductal lesions is pathological nipple discharge (PND), although many patients with intraductal lesions do not exhibit PND. It is a serious challenge for clinicians to detect patients with intraductal lesions without PND at an early stage. The aim of the present study was to investigate the risk factors associated with intraductal lesions in patients without PND. This retrospective database review, conducted between April 2016 and April 2017, included 370 lesions from 255 patients with intraductal lesions (intraductal papilloma, atypical intraductal hyperplasia, intraductal carcinoma in situ) and non-intraductal lesions (fibroadenoma, adenosis, cysts, lobular carcinoma in situ), diagnosed through surgical pathology. The patients were divided into two groups based on pathological diagnosis and clinical parameters were evaluated using univariate and multivariate analyses. Univariate analysis revealed that 9 of 14 factors were statistically significant. Five factors were identified to be associated risk factors in patients without PND through the multivariate logistic regression analysis: Age between 35 and 49 years and age ≥50 years [odds ratio (OR)=4.749, 95% confidence interval (CI)=2.371-9.513, P<0.001; OR=2.587, 95% CI=2.587-14.891, P<0.001; respectively], non-menstrual breast pain (OR=1.922, 95% CI=1.037-3.564, P=0.038), breast duct dilatation as seen using ultrasonography (OR=9.455, 95% CI=3.194-27.987, P<0.001), lesion distance from nipple ≤2 cm (OR=2.747, 95% CI=1.668-4.526, P<0.001) and lesion size ≤1 cm (OR=1.903, 95% CI=1.155-3.136, P=0.012). In conclusion, for patients without PND but with risk factors, such as the patient being >35 years, with non-menstrual breast pain, breast duct ectasia, lesion distance from nipple ≤2 cm and lesion size ≤1 cm as seen using ultrasonography, clinicians should be highly concerned about the possibility of intraductal lesions, in order to prevent misdiagnosis and reduce the misdiagnosis rate.

Downregulation of the long non-coding RNA TUG1 is associated with cell proliferation, migration, and invasion in breast cancer.

Recent studies have identified many long non-coding RNAs (lncRNAs) with critical roles in various biological processes including tumorigenesis. Taurine-upregulated gene 1 (TUG1), is an lncRNA recently reported to be involved in the progression of several human cancers. This study aimed to investigate the clinical significance and biological functions of TUG1 in breast cancer. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure TUG1 expression in cells from breast cancer cell lines and in 58 matched pairs of breast cancer and normal tissue samples from patients with clinicopathological comparisons. Gain-and loss-of-function experiments were performed in vitro to investigate the biological role of TUG1. TUG1 expression was significantly downregulated in both breast cancer tissues and cell lines compared to controls, and low TUG1 expression was significantly correlated with mutant p53 expression (p=0.037) and lymph node metastasis (p=0.044). In vitro experiments revealed that TUG1 overexpression significantly suppressed cell proliferation by causing cell cycle arrest and inducing apoptosis in breast cancer cells, while TUG1 knockdown caused increased cell growth via promoting cell cycle progression and regulating the expression of cyclinD1 and CDK4. Further functional assays indicated that TUG1 overexpression significantly promoted cell migration and invasion while TUG1 knockdown had the opposite effects. Our findings indicate that the lncRNA TUG1 is a tumor suppressor in breast cancer, and may serve as a novel prognostic biomarker and potential therapeutic target for patients with breast cancer.