these results are the first to indicate that the KRAS 3'UTR polymorphism may predict for cetuximab responsiveness in KRASwt mCRC patients, which warrants validation in other clinical trials.

Background Whether tumour-infiltrating lymphocytes (TILs) play different roles in different molecular subtypes of breast cancer remains unknown. Additionally, their prognostic and predictive value in different molecular subtypes of breast cancer is still controversial. The aim of our meta-analysis was to assess the prognostic and predictive value of TILs in different molecular subtypes of breast cancer by summarizing all relevant studies performing multivariate analysis. Methods PubMed, Embase, EBSCO, ScienceDirect, the Cochrane Database and Web of Science were comprehensively searched (until March 2020). Hazard ratios (HRs), odds ratios (ORs) and their 95% confidence intervals (CIs) were used as effect measures to perform our meta-analysis. A random effect model was used. Stata software, version 15 (2017) (StataCorp, College Station, TX, USA) was used to perform the statistical analysis. Results Thirty-three studies including 18,170 eligible breast cancer patients were analysed. The meta-analysis showed that high TIL expression was significantly associated with increased pathological complete response (pCR) rates after neoadjuvant chemotherapy in patients with the HER2-enriched molecular subtype (OR = 1.137, 95% CI [1.061 ~ 1.218], p < 0.001) and triple-negative breast cancer (TNBC) subtype (OR = 1.120, 95% CI [1.061 ~ 1.182], p < 0.001). However, high TIL expression was not significantly associated with high pCR rates after neoadjuvant chemotherapy in patients with the luminal molecular subtype of breast cancer (OR = 1.154, 95% CI [0.789 ~ 1.690], p = 0.460). We carried out a meta-analysis on the HRs of overall survival (OS) and disease-free survival (DFS) to assess the prognostic value of TILs in breast cancer with different molecular subtypes more deeply. Our meta-analysis confirmed that high TILs were associated with significantly improved DFS in patients with the HER2-enriched molecular subtype [HR = 0.940, 95% CI (0.903 ~ 0.979), p = 0.003] and TNBC molecular subtype [HR = 0.907, 95% CI (0.862 ~ 0.954), p < 0.001]. However, high TILs were not associated with significantly better DFS in patients with the luminal molecular subtype of breast cancer [HR = 0.998, 95% CI (0.977 ~ 1.019), p = 0.840]. Furthermore, the results confirmed that high TILs were significantly related to better OS in patients with the HER2-enriched molecular subtype [HR = 0.910, 95% CI (0.866 ~ 0.957), p < 0.001] and TNBC molecular subtype [HR = 0.869, 95% CI (0.836 ~ 0.904), p < 0.001]. Conversely, the summarized results indicated that high TILs were significantly associated with poor OS in patients with the luminal molecular subtype of breast cancer [HR = 1.077, 95% CI (1.016 ~ 1.141), p = 0.012]. Conclusions Our meta-analysis confirms that high TILs are associated with favourable survival and predicts pCR in breast cancer patients with the TNBC and HER2-enriched molecular subtypes.

BackgroundThe prognostic significance of FOXP3+ tumor-infiltrating lymphocytes (TILs) in patients with breast cancer remains controversial. The aims of our meta-analysis are to evaluate its association with clinicopathological characteristics and prognostic significance in patients with breast cancer.MethodsPubMed, Embase, Cochrane Database and the Ovid Database were systematically searched (up to April 2015). The meta-analysis was performed using hazard ratio (HR), odds ratio (OR) and 95 % confidence intervals (CI) as effect measures. Using the random-effects model, statistical analysis was performed using Stata software, version 12.0.ResultsSeventeen studies including 8277 patients with breast cancer were analyzed. The meta-analysis indicated that the incidence difference of FOXP3+ TILs was significant when comparing the lymph node positive group to negative group (OR = 1.305, 95 % CI [1.071, 1.590]), the histological grade III group to the I–II group (OR = 3.067, 95 % CI [2.288, 4.111]), the ER positive group to the negative group (OR = 0.435, 95 % CI [0.287, 0.660]), the PR positive group to the negative group (OR = 0.493, 95 % CI [0.296, 0.822]), the HER2 positive group to the negative group (OR = 1.896, 95 % CI [1.335, 2.692]), the TNBC group to the non TNBC group (OR = 2.456, 95 % CI [1.801, 3.348]). The detection of FOXP3+ TILs was significantly correlated with the recurrence-free survival (RFS) of patients (HR = 1.752, 95 % CI [1.188–2.584]) and the overall survival (OS) of patients (HR =1.447, 95 % CI [1.037–2.019]).ConclusionsOur meta-analysis demonstrates that the presence of high levels of FOXP3+ TILs is associated with prognosis for breast cancer patients and predicts lymph node metastasis, hormone receptor and HER-2 status.

Background. Acetone, β-hydroxybutyric acid, and acetoacetic acid are three types of ketone body that may be found in the breath, blood, and urine. Detecting altered concentrations of ketones in the breath, blood, and urine is crucial for the diagnosis and treatment of diabetic ketosis. The aim of this study was to evaluate the advantages of different detection methods for ketones, and to establish whether detection of the concentration of ketones in the breath is an effective and practical technique. Methods. We measured the concentrations of acetone in the breath using gas chromatography-mass spectrometry and β-hydroxybutyrate in fingertip blood collected from 99 patients with diabetes assigned to groups 1 (−), 2 (±), 3 (+), 4 (++), or 5 (+++) according to urinary ketone concentrations. Results. There were strong relationships between fasting blood glucose, age, and diabetic ketosis. Exhaled acetone concentration significantly correlated with concentrations of fasting blood glucose, ketones in the blood and urine, LDL-C, creatinine, and blood urea nitrogen. Conclusions. Breath testing for ketones has a high sensitivity and specificity and appears to be a noninvasive, convenient, and repeatable method for the diagnosis and therapeutic monitoring of diabetic ketosis.

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Our findings indicate that cytoplasmic ILEI expression is a potential marker of EMT and tumour progression in CRC. ILEI is an independent predictive factor associated with poor prognosis in CRC.

β-catenin, an epithelial-mesenchymal transition (EMT)-associated marker, is key in the progression of colorectal cancer (CRC). However, the prognostic significance of β-catenin expression in patients with CRC remains controversial. In the present study, the expression of β-catenin at the tumor invasive front and the tumor center was investigated, and the correlations amongst β-catenin differential expression patterns and the clinicopathological characteristics and prognosis of CRC patients were determined. In total, 181 patients that were diagnosed with CRC (as determined by histopathological evaluation) and subjected to surgical resection at the First Hospital of China Medical University between 2000 and 2001 were examined, and CRC specimens were obtained. Immunohistochemical (IHC) staining of β-catenin was performed for each specimen. The nuclear β-catenin expression levels were identified to be significantly lower in the tumor center than at the tumor invasive front (immunoreactivity score, 0.05±0.303 versus 2.18±3.917; P<0.001). The presence of nuclear β-catenin overexpression at the tumor invasive front was found to be correlated with the tumor, node, metastasis stage (P=0.020), lymph node metastasis (P=0.016) and histological differentiation (P=0.006). Survival analysis revealed that reduced membranous expression levels and increased nuclear expression levels of β-catenin were statistically significantly associated with poor survival times. Furthermore, differential β-catenin expression levels were associated with aggressive morphological features, EMT and a poor prognosis in CRC. Therefore, IHC analysis of β-catenin is considered to be a useful marker to predict the prognosis in patients with CRC.

Bcl2-associated athanogene (BAG)2 as a co-chaperone has been demonstrated to be involved in tumor growth and metastasis, but its biological function in gastric cancer remains unknown. Here, we reported that BAG2 was highly expressed in gastric cancer cell lines and tissues, indicating poor prognosis. High expression of BAG2 was significantly associated with T stage and differentiation level of gastric cancer (P < 0.001). Functional experiments revealed that BAG2 knockdown in gastric cancer cells inhibited the proliferation, invasion and migration of cells through AKT/mTOR and extracellular regulated kinase (ERK) pathways. Proteomic analysis identified that BAG2 may be involved in the regulation of mitogen-activated protein kinase (MAPK) pathway. In addition, immunoprecipitation showed that BAG2 could bind to ERK1/2. Luciferase reporter assay and Western blot verified that BAG2 was down-regulated by miR186. Taken together, our findings may reveal the basic function of BAG2 and uncover a potential therapeutic target for gastric cancer.