Expression and clinical significance of hypoxia-induced long non-coding RNA TCONS_I2_00001955 in breast cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been found to play important roles in occurrence, development, and metastasis of various tumors. We aimed to screen long non-coding RNAs (lncRNAs) that promote invasion and metastasis of breast cancer cells under hypoxia, and investigate the relationship between lncRNA expression and clinicopathological features and prognosis in invasive breast cancer. METHODS: LncRNA microarray was used to screen the differentially expressed lncRNAs in MCF7, MDA-MB-231, and SKBR3 breast cancer cell lines cultured under normoxia and hypoxia, respectively. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to verify the microarray results. CCK8 and Transwell experiments were performed to identify the lncRNA that promote proliferation, migration, and invasion of breast cancer cells. Expression of the lncRNA and HIF-1α in invasive breast cancer was detected by RNAscope and immunohistochemistry, respectively. Correlation between the lncRNA expression and baseline characteristics was analyzed. Prognostic value of the lncRNA was evaluated using univariate and multivariate Cox regression. RESULTS: Expression of lncRNA TCONS_I2_00001955 in all the three breast cancer cells was increased under hypoxia. Overexpression of TCONS_I2_00001955 significantly enhanced proliferation, migration, and invasion of SKBR3 cells. Positive expression of TCONS_I2_00001955 was associated with recurrence, metastasis, and high expression of HIF-1α (P < 0.05), and it was an independent risk factor for poor disease-free survival of breast cancer. CONCLUSION: Hypoxia-induced lncRNA TCONS_I2_00001955 was associated with aggressive feature and poor prognosis of breast cancer.

A Myeloid Signature-Based Nomogram Predicts the Postoperative Recurrence of Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is the second most common cancer in liver, with a high recurrence rate after surgery. Recently, we identified a CD11b-CD169-based myeloid response score (MRS), which showed remarkable prognostic potential in hepatocellular carcinoma (HCC). Here, we aimed to verify the prognostic value of the MRS in iCCA and establish an MRS-based nomogram to predict the postoperative prognosis of iCCA patients. From April 2005 to March 2017, a total of 84 patients from the Third Affiliated Hospital of Sun Yat-sen University were enrolled. Preoperative clinical information and surgical specimens of enrolled patients were collected. Among these, tissues from 75 patients passed the clinical data quality control and the staining quality control. The protein expression of CD11b and CD169 in iCCA samples were detected by immunohistochemistry (IHC). Kaplan-Meier analysis and receiver operating characteristic (ROC) curves revealed that the MRS had a high discriminatory ability for predicting the time to recurrence (TTR) of iCCA patients after surgery. Three independent risk factors selected by a Cox proportional hazards regression analysis, namely, the MRS, the tumor size and the status of vascular invasion, were included to construct a nomogram to predict the recurrence of iCCA after resection surgery. ROC curves, calibration analysis and decision curve analysis (DCA) suggested that this nomogram had notable discriminatory power, stability and clinical usefulness in predicting the postoperative recurrence. Together, we explored the prognostic value of the MRS in iCCA, and constructed an MRS-based nomogram which may help to predict postoperative recurrence and aid clinical decisions for iCCA patients.

Expression pattern of cancer-associated fibroblast and its clinical relevance in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and lack of effective treatment, characterized by dense desmoplastic stroma rich in cancer-associated fibroblasts (CAFs), which have been indicated to facilitate tumor progression in several types of human cancer. However, the clinical relevance of CAFs in ICC has not been fully characterized. Here, we evaluated the histological phenotype of CAFs and immunohistochemical expressions of α-SMA, FSP-1, and PDGFRß in 71 ICC cases, and found that immature CAF phenotype was significantly associated with lymph node metastasis (P=.045), advanced TNM stage (P=.025) and poor 5-year overall survival (OS) (38.5% versus 78.6%, P=.015). In addition, α-SMA, FSP-1, and PDGFRß were positively expressed in stromal fibroblasts in 63.4% (45/71), 84.5% (60/71), and 78.9% (56/71) of patients, respectively. Positive expression of α-SMA was correlated with poor differentiation (P=.032); FSP-1 expression in stromal fibroblasts was linked with lymph node metastasis (P=.022) and immature phenotype (P=.048). What's more, positive expression of FSP-1 in cancer cells was observed in 22.5% (16/71) of cases and was correlated with worse 5-year OS (36.4% versus 76.7%, P=.014). Importantly, in multivariate analysis, histological CAF phenotype was an independent prognostic factor for OS in ICC. Our findings demonstrated histological categorization of CAFs was a useful predictor for prognosis, providing new evidence that CAFs play a crucial role in tumor progression and can serve as potential therapeutic targets in ICC.