Xiuxiu Hu

Platelet‐to‐lymphocyte ratio could be a promising prognostic biomarker for survival of colorectal cancer: a systematic review and meta‐analysis

Inflammation is one of the most important causes leading to colorectal carcinogenesis, and inflammatory biomarkers such as the platelet‐to‐lymphocyte ratio (PLR) might predict survival in colorectal cancer (CRC). However, the prognostic value of PLR in CRC patients remains controversial. The prognostic value of PLR was comprehensively analyzed in 12 articles including 3541 CRC patients (10 for overall survival (OS), seven for disease‐free survival (DFS), three for recurrence‐free survival (RFS), and three for cancer‐specific survival (CSS)) in this study. The overall pooled hazard ratios (HRs) of PLR for OS, DFS, and CSS were significant at 1.29 (95% confidence interval, CI = 1.13–1.47, PH = 0.149), 1.43 (95% CI = 1.03–1.97, PH = 0.025), and 1.26 (95% CI = 1.04–1.52, PH = 0.223), respectively. However, there was no evidence of significance for RFS (HR = 1.29, 95% CI = 0.98–1.70, PH = 0.231) in our study. Stratified analyses indicated elevated PLR was a predictor of poor OS (metastatic patients) and DFS (Caucasian population) and was also significantly associated with OS in univariate analysis (HR = 1.35, 95% CI = 1.14–1.60, PH = 0.532) and those only treated surgically (HR = 1.37, 95% CI = 1.10–1.70, PH = 1.080). However, our findings indicated that elevated PLR is a promising prognostic biomarker for colorectal cancer, especially in metastatic Caucasian CRC patients.

MicroRNA expression profiles predict progression and clinical outcome in lung adenocarcinoma

Lung cancer is one of the leading causes of cancer death worldwide. Accumulating evidence has indicated that microRNAs (miRNAs) can be proposed as promising diagnostic and prognostic markers for various cancers. The current study analyzed the miRNA expression profiles of 418 lung adenocarcinoma (LUAD) cases obtained from The Cancer Genome Atlas dataset, with the aim to investigate the relationship of miRNAs with progression and prognosis of LUAD. A total of 185 miRNAs were found to be differentially expressed between LUAD tumor tissues and adjacent normal tissues. Among them, 13, 10, 0, and 10 miRNAs were discovered to be associated with pathologic T, N, M, and Stage, respectively. Interestingly, mir-200 family (mir-200a, mir-200b, and mir-429) was shown to play a critical role in the progression of LUAD. In the multivariate Cox regression analysis, mir-1468 (P=0.009), mir-212 (P=0.026), mir-3653 (P=0.012), and mir-31 (P=0.002) were significantly correlated with recurrence-free survival. With regard to overall survival, mir-551b (P=0.011), mir-3653 (P=0.016), and mir-31 (P=0.001) were proven as independent prognostic markers. In summary, this study identified the cancer-specific miRNAs that may predict the progression and prognosis of LUAD.

Combination of preoperative NLR, PLR and CEA could increase the diagnostic efficacy for I-III stage CRC.

Inflammation plays an important role in the development and progression of CRC. The members of inflammatory biomarkers, preoperative NLR and PLR, have been proved by numerous studies to be promising prognostic biomarkers for CRC. However, the diagnostic value of the two biomarkers in CRC remains unknown, and no study reported the combined diagnostic efficacy of NLR, PLR and CEA.

Association between SNPs in Long Non-coding RNAs and the Risk of Female Breast Cancer in a Chinese Population

Long non-coding RNAs (LncRNAs) have been reported to be involved in tumorigenesis and tumor progression. Single nucleotide polymorphisms (SNPs) in the lncRNAs also play a vital role in carcinogenesis. The aim of this study was to assess the relationships between the four selected tagSNPs (rs944289, rs3787016, rs1456315, rs7463708) in the lncRNAs and the risk of female breast cancer in a Chinese population. A case-control study was carried out involving in a total of 439 breast cancer patients and 439 age-matched healthy controls. The genotyping was performed with Sequenom MassARRAY and the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) in tumor tissues was measured by the immunohistochemistry (IHC) assay. We found that rs3787016 TT genotype (adjusted odds ratio (OR) = 1.62, 95% confidence interval (CI) = 1.09-2.41, P = 0.018) was associated with an increased risk of female breast cancer, especially among the patients with premenopausal status (adjusted OR = 2.55, 95% CI = 1.30-4.97, P = 0.006). Moreover, a statistically significant increased risk of the rs3787016 TT genotype was observed among the patients with advanced tumor stage (Ⅲ and Ⅳ), poor histological grade (G3-G4), positive lymph node involvement, positive expression of ER and PR and negative expression of HER-2; rs7463708 GT and GT/GG genotype were associated with decreased risk of breast cancer in the subgroup of patients with postmenopausal status (GT versus (vs.) TT: adjusted OR = 0.67, 95% CI = 0.46-0.99, P = 0.043; GT/GG vs. TT: adjusted OR = 0.68, 95% CI = 0.47-0.98, P = 0.041) and tumor late-stage (GT vs. TT: adjusted OR = 0.65, 95% CI = 0.43-0.97, P = 0.037; GT/GG vs. TT: adjusted OR = 0.65, 95% CI = 0.44-0.96, P = 0.029). In short, rs3787016 TT genotype was associated with increased breast cancer risk and clinicopathologic features of the tumor, especially among premenopausal women.

A nomogram based on serum bilirubin and albumin levels predicts survival in gastric cancer patients

Decreases in serum bilirubin and albumin levels are associated with poorer prognoses in some types of cancer. Here, we examined the predictive value of serum bilirubin and albumin levels in 778 gastric cancer patients from a single hospital in China who were divided among prospective training and retrospective validation cohorts. X-tile software was used to identify optimal cutoff values for separating training cohort patients into higher and lower overall survival (OS) groups, based on total bilirubin (TBIL) and albumin levels. In univariate analysis, tumor grade and TNM stage were associated with OS. After adjusting for tumor grade and TNM stage, TBIL and albumin levels were still clearly associated with OS. These results were confirmed in the 299 patients in the validation cohort. A nomogram based on TBIL and albumin levels was more accurate than the TNM staging system for predicting prognosis in both cohorts. These results suggest that serum TBIL and albumin levels are independent predictors of OS in gastric cancer patients, and that an index that combines TBIL and albumin levels with the TNM staging system might have more predictive value than any of these measures alone.

The Predictive and Prognostic Role of Stromal Tumor-infiltrating Lymphocytes in HER2-positive Breast Cancer with Trastuzumab-based Treatment: a Meta-analysis and Systematic Review

Background Tumor-infiltrating lymphocytes (TILs) are white blood cells that have left the bloodstream and migrated into a tumor, involving in the prognosis of breast cancer (BC) patients. Published studies reported the value of TILs in patients with HER2-positive receiving trastuzumab-based treatment. However, the results obtained remain controversial. Here, we conducted this study to explore the predictive and prognostic role of TILs for HER2-positive BC patients receiving trastuzumab therapies. Method To identify the related published studies, a comprehensive literature search dating up to July 2017 was performed in the databases of PubMed, PMC, Web of Science and China National Knowledge Infrastructure (CNKI) according to predefined selection criteria. The pathologic complete response (pCR) and survival outcome of patients were measured by odds ratio (OR) and hazard ratio (HR) with corresponding 95% confidence interval (95% CI), respectively. The association between TILs and trastuzumab benefit was analyzed by using STATA version 11.0. Result Eleven eligible studies comprising 3228 patients were identified in the present study. The pooled results showed that high level of TILs was associated with a significantly improved pCR rate (OR = 1.32; 95% CI = 1.10-1.60) and longer survival (HR = 0.97; 95% CI = 0.96-0.99), particularly in the subgroups of retrospective study design and 10% INC cut-off value. Moreover, stratified analysis revealed that elevated TILs was a predictor of higher pCR rate in the Asian population and improved survival in the subgroups of Caucasian population and multivariate analysis. Conclusion This meta-analysis indicated that the level of stromal TILs was an independent predictive and prognostic marker for better outcome in HER2-positive BC patients receiving trastuzumab-based treatment. High level of TILs was significantly associated with trastuzumab benefit.

microRNA-485-5p Functions as a Tumor Suppressor in Colorectal Cancer Cells by Targeting CD147

Colorectal cancer(CRC) is a prevalent malignancy in the world. There is growing evidence that microRNAs (miRNAs) as crucial modulator are in connection with many tumor-related diseases including CRC. Though miR-485-5p has been reported as an anti-oncogene in certain cancers, it remains unclear in CRC. In this research, we found that miR-485-5p was at lower level expression in CRC tissues and cell lines compared to the paired paracancerous tissues and the normal colon epithelial cell line FHC, correspondingly. Furthermore, Experimental up-regulation miR-485-5p in DLD-1 and SW480 cells with mimic could inhibit the ability of proliferation, migration, invasion of CRC cell lines and facilitate cells apoptosis. Also, we confirmed that CD147 existed typically negative regulation by miR-485-5p through binding a conserved sequence specifically within the CD147 3′-untranslated region (3′UTR) and reintroduction of CD147 could rescue the phenotypic changes caused by miR-485-5p. The findings provide evidence to demonstrate the role of miR-485-5p/CD147 interaction in CRC and indicate that miR-485-5p might be exploited therapeutically in CRC.

The long noncoding RNA SNHG1 regulates colorectal cancer cell growth through interactions with EZH2 and miR-154-5p

BackgroundMounting evidence demonstrates that long noncoding RNAs (lncRNAs) have critical roles during the initiation and progression of cancers. In this study, we report that the small nucleolar RNA host gene 1 (SNHG1) is involved in colorectal cancer progression.MethodsWe analyzed RNA sequencing data to explore abnormally expressed lncRNAs in colorectal cancer. The effects of SNHG1 on colorectal cancer were investigated through in vitro and in vivo assays (i.e., CCK-8 assay, colony formation assay, flow cytometry assay, EdU assay, xenograft model, immunohistochemistry, and western blot). The mechanism of SNHG1 action was explored through bioinformatics, RNA fluorescence in situ hybridization, luciferase reporter assay, RNA pull-down assay, chromatin immunoprecipitation assay and RNA immunoprecipitation assay.ResultsOur analysis revealed that SNHG1 was upregulated in human colorectal cancer tissues, and high SNHG1 expression was associated with reduced patient survival. We also found that high SNHG1 expression was partly induced by SP1. Moreover, SNHG1 knockdown significantly repressed colorectal cancer cells growth both in vitro and in vivo. Mechanistic investigations demonstrated that SNHG1 could directly interact with Polycomb Repressive Complex 2 (PRC2) and modulate the histone methylation of promoter of Kruppel like factor 2 (KLF2) and Cyclin dependent kinase inhibitor 2B (CDKN2B) in the nucleus. In the cytoplasm, SNHG1 acted as a sponge for miR-154-5p, reducing its ability to repress Cyclin D2 (CCND2) expression.ConclusionsTaken together, the results of our studies illuminate how SNHG1 formed a regulatory network to confer an oncogenic function in colorectal cancer and suggest that SNHG1 may serve as a potential target for colorectal cancer diagnosis and treatment.

MiR-490-3p Functions As a Tumor Suppressor by Inhibiting Oncogene VDAC1 Expression in Colorectal Cancer

Colorectal cancer (CRC) is one of the most common cancers worldwide, usually with poor prognosis because many CRC patients are diagnosed at an advanced stage. Therefore, novel potential diagnostic and prognostic biomarkers are urgently needed. MicroRNAs have been reported to regulate a variety of biological processes, such as cell proliferation, differentiation and apoptosis. Accumulating studies have demonstrated that miR-490-3p could regulate the development and progression of multiple cancers, but its clinical significance and molecular mechanism in CRC are still elusive. Here, we try to further elucidate the regulatory mechanism of miR-490-3p in CRC. In the present study, miR-490-3p expression level observably down-regulated in CRC tissues and cell lines, and miR-490-3p expression in CRC tissues was significantly associated with TNM stage, histological grade, tumor size and overall survival (OS). In addition, we observed miR-490-3p expression was also decreased in CRC plasmas and could act as a promising diagnostic biomarker for screening CRC. Further studies in vitro demonstrated Voltage Dependent Anion Channel 1 (VDAC1) which highly expressed in CRC tissues and cell lines is a direct target of miR-490-3p, and miR-490-3p could markedly inhibit CRC cells proliferation, metastasis, invasion and anti-apoptosis through suppressing VDAC1/AMPK/mTOR pathway. These results indicated that miR-490-3p functions as a tumor suppressor in CRC, and may be a novel potential diagnostic and prognostic biomarker for CRC.

SP1-induced lncRNA-ZFAS1 contributes to colorectal cancer progression via the miR-150-5p/VEGFA axis

Increasing long non-coding RNAs (lncRNAs) have been reported to play key roles in the development and progression of various malignancies. ZNFX1 antisense RNA1 (ZFAS1) has been reported to be aberrant expression and suggested as a tumor suppressor or oncogene in many cancers. However, the biological role and underlying molecular mechanism of ZFAS1, especially the miRNA sponge role of which in CRC remain largely unknown. We found that ZFAS1 expression was higher in CRC tissues, where it was associated with poor overall survival (OS), we also showed that ZFAS1 upregulation was induced by nuclear transcription factor SP1. Moreover, ZFAS1 and VEGFA are both targets of miR-150-5p, while ZFAS1 binds to miR-150-5p in an AGO2-dependent manner. Additionally, ZFAS1 upregulation markedly promoted as well as ZFAS1 knockdown significantly suppressed CRC cell proliferation, migration, invasion and angiogenesis, and the inhibitory effect caused by ZFAS1 knockdown could be reversed by antagomiR-150-5p. Lastly, we demonstrated that ZFAS1 knockdown inhibited EMT process and inactivated VEGFA/VEGFR2 and downstream Akt/mTOR signaling pathway in CRC. Our data demonstrated that SP1-induced ZFAS1 contributed to CRC progression by upregulating VEGFA via competitively binding to miR-150-5p, which acts as a tumor suppressor by targeting VEGFA in CRC.