Correlation Between Adjuvant Chemotherapy Regimen, Recurrence Pattern and Prognosis of Cholangiocarcinoma After Radical Surgery.

BACKGROUND AND PURPOSE: About 70% of patients with radical surgery Cholangiocarcinoma (CCA) have recurrence and metastasis. There are few studies on the relationship between CCA adjuvant chemotherapy (mono or combined therapy), recurrence pattern (local, regional, distant recurrence) and prognosis [(Disease free survival, DFS), (Overall survival, OS)] after radical surgery. This study focuses on the correlation between CCA adjuvant chemotherapy, recurrence pattern and prognosis. METHODS: The study involved retrospective analysis of data: preoperative hematology, clinical pathology, adjuvant chemotherapy regimens, recurrence pattern, DFS and OS, of 207 patients with CCA. Chi-square test was used to analyze the correlation between related factors and postoperative recurrence. Survival curves were plotted by Kaplan-Meier method, P-values were calculated by Log-rank for univariate analysis, multivariate COX regression method for multivariate analysis. RESULTS: Using chi-square test, there were correlations between high carbohydrate antigen 19-9 level(CA19-9≥35), vascular invasion, single-agent adjuvant chemotherapy and postoperative recurrences (p=0.04, p=0.04, p=0.02), COX multivariate regression analysis showed that adjuvant chemotherapy (single vs. doublet drug regimen) was an independent prognostic factor for DFS (11.0 vs. 24.6 months, HR=2.88, P=0.01), whereas recurrence pattern (local vs. distant; regional vs. distant) was an independent prognostic factor for OS (31.2 months vs. 20.4 months, HR=0.58, p=0.01; 32.0 months vs. 20.4 months, HR=0.51, p=0.01). CONCLUSION: Adjuvant chemotherapy regimen was an independent prognostic factor of DFS, whereas recurrence patterns were independent prognostic factors for OS. adjuvant chemotherapy with doublet drug regimen was correlated with longer DFS, and different recurrence modes affect OS.

Cell-free DNA methylation markers for differential diagnosis of hepatocellular carcinoma.

BACKGROUND: Aberrant DNA methylation may offer opportunities in revolutionizing cancer screening and diagnosis. We sought to identify a non-invasive DNA methylation-based screening approach using cell-free DNA (cfDNA) for early detection of hepatocellular carcinoma (HCC). METHODS: Differentially, DNA methylation blocks were determined by comparing methylation profiles of biopsy-proven HCC, liver cirrhosis, and normal tissue samples with high throughput DNA bisulfite sequencing. A multi-layer HCC screening model was subsequently constructed based on tissue-derived differentially methylated blocks (DMBs). This model was tested in a cohort consisting of 120 HCC, 92 liver cirrhotic, and 290 healthy plasma samples including 65 hepatitis B surface antigen-seropositive (HBsAg+) samples, independently validated in a cohort consisting of 67 HCC, 111 liver cirrhotic, and 242 healthy plasma samples including 56 HBsAg+ samples. RESULTS: Based on methylation profiling of tissue samples, 2321 DMBs were identified, which were subsequently used to construct a cfDNA-based HCC screening model, achieved a sensitivity of 86% and specificity of 98% in the training cohort and a sensitivity of 84% and specificity of 96% in the independent validation cohort. This model obtained a sensitivity of 76% in 37 early-stage HCC (Barcelona clinical liver cancer [BCLC] stage 0-A) patients. The screening model can effectively discriminate HCC patients from non-HCC controls, including liver cirrhotic patients, asymptomatic HBsAg+ and healthy individuals, achieving an AUC of 0.957(95% CI 0.939-0.975), whereas serum α-fetoprotein (AFP) only achieved an AUC of 0.803 (95% CI 0.758-0.847). Besides detecting patients with early-stage HCC from non-HCC controls, this model showed high capacity for distinguishing early-stage HCC from a high risk population (AUC=0.934; 95% CI 0.905-0.963), also significantly outperforming AFP. Furthermore, our model also showed superior performance in distinguishing HCC with normal AFP (< 20ng ml-1) from high risk population (AUC=0.93; 95% CI 0.892-0.969). CONCLUSIONS: We have developed a sensitive blood-based non-invasive HCC screening model which can effectively distinguish early-stage HCC patients from high risk population and demonstrated its performance through an independent validation cohort. TRIAL REGISTRATION: The study was approved by the ethic committee of The Second Xiangya Hospital of Central South University (KYLL2018072) and Chongqing University Cancer Hospital (2019167). The study is registered at ClinicalTrials.gov(# NCT04383353 ).

Individualized comprehensive treatment for lung adenocarcinoma with multiple skin and bilateral breast metastasis: A case report. / å¤šæ¬¡çš®è‚¤å’ŒåŒä¾§ä¹³è ºè½¬ç§»çš„è‚ºè ºç™Œä¸ªä½“åŒ–ç»¼åˆæ²»ç–—1例.

Lung adenocarcinoma is a malignant tumor that is prone to distant metastasis. Common metastatic sites are brain, adrenal gland, liver, bone, and so on. Skin soft tissue metastasis is unusual, and breast metastasis is even rarer. This case is a middle-aged female patient who had experienced multi-line treatments for upper limbs, abdominal skin, and bilateral breast tissue metastases.The patient's multiple metastases were susceptible to radiation therapy.Reviewing the entire treatment process of this patient can find that the rational use of individualized comprehensive treatment methods and appropriate timing of genetic testing are very important for patients with lung adenocarcinoma to prolong their survival time and improve their quality of life.

Clinical and prognostic features of 512 cases of cholangiocarcinoma. / 512例胆管细胞癌的临床及预后特点.

OBJECTIVES: Cholangiocarcinoma (CCA) is an aggressive malignant tumor with a poor overall prognosis. Given that CCA is often diagnosed at the late stage, the current treatments are less effective for most local advanced patients leading to high CCA mortality. This study aims to explore the clinical characteristics and prognostic factors affecting the occurrence and development of CCA and to provide potential methods for early diagnosis and clinical treatment of CCA. METHODS: We retrospectively analyzed the medical records of 512 patients with CCA who had been diagnosed by pathology and had completely clinical data in the Second Xiangya Hospital of Central South University in the past 16 years. The clinical features and prognosis related factors that affect the occurrence and development of CCA were investigated. Survival curves were plotted by the Kaplan-Meier method. P-values were calculated by log-rank for univariate analysis, and multivariate Cox regression was used to analyze multivariate analysis of meaningful variables. RESULTS: The incidence of CCA among ≤60 years old people was higher than of that >60 years old one (61.13% vs 38.87%), and was greater in men than women (52.5% vs 47.5%). Carbohydrate antigen 19-9 (CA19-9) level ≥35 µg/L accounted for 66.21%. The single tumor accounted for 86.91%, and patients in pathological stage III and IV accounted for 49.22% and 17.58%, respectively. Univariate analysis showed that ALB, ALP, CA19-9, and other factors were relevant to the prognosis. The results of multivariate analysis showed that ALP, CA19-9, tmaximum tumor diameter, and other factors were significant prognostic predictors. CONCLUSIONS: The incidence of CCA is higher in ≤60 years old people, and the stage is later at the initial diagnosis. CA19-9 level is a sensitive laboratory indicator. ALP, CA19-9, maximum tumor diameter, merged tumor, cirrhosis, and TNM stage are independent prognostic factors for CCA.

Long non-coding RNA NKILA inhibited angiogenesis of breast cancer through NF-κB/IL-6 signaling pathway.

OBJECTIVE: The relationship between NF-κB Interacting lncRNA (NKILA) and angiogenesis in breast cancer has never been studied. Our study aimed to investigate effect of NKILA on proliferation, migration, apoptosis, as well as angiogenesis in breast cancer. METHODS: NKILA was over-expressed in MDA-MB-231 cells by transfection of pcDNA3.1-NKILA vector. Cell viability, apoptosis and migration were measured by MTT, flow cytometry and wound healing assays, respectively. Angiogenesis of human umbilical vein endothelial cells (HUVEC) was measured using tube formation assay. The expression levels of NKILA, IL-6, VEGFA, VEGFR, apoptosis and epithelial-mesenchymal transition (EMT) and NF-κB/IL-6 signaling-related markers were determined using qRT-PCR or Western blotting. RESULTS: Cell viability and migration of MDA-MB-231 cells were significantly inhibited, while cell apoptosis was obviously promoted by overexpression of NKILA. Overexpression of NKILA could also inhibit the phosphorylation of IκBα and the nuclear transposition of p65, as well as induce cell apoptosis-related proteins and inhibit epithelial-mesenchymal transition-related proteins. Cell viability and migration of HUVEC were also significantly inhibited when treated with supernatant of cells overexpressed NKILA or treated with BAY11-7028. Exogenous IL-6 significantly increased the cell viability and migration of HUVEC, and overexpression of NKILA could reverse these effects induced by IL-6. Overexpression of NKILA significantly inhibited the protein levels of IL-6 and VEGFA in supernatant, as well as VEGFR in HUVEC, thus inhibited the angiogenesis of HUVEC. NKILA also reversed the above effects on protein levels of IL-6 and VEGFA in supernatant and angiogenesis induced by exogenous IL-6. CONCLUSION: Overexpression of NKILA could inhibit cell proliferation, migration and promote apoptosis of breast cancer cells. It could also inhibit cell proliferation, migration and angiogenesis of HUVEC through inhibiting IL-6 secretion via NF-κB signaling pathway.

Sp1-induced upregulation of the long noncoding RNA TINCR inhibits cell migration and invasion by regulating miR-107/miR-1286 in lung adenocarcinoma.

Long non-coding RNA tissue differentiation-inducing non-protein coding (TINCR) is associated with the carcinogenesis of several cancers. However, little is known about the function and mechanism of TINCR in lung adenocarcinoma (LUAD). Here, we aimed to analyze expression of TINCR and elucidate its mechanistic involvement in the progression of LUAD. The expression of TINCR was investigated according to Gene Expression Profiling Interactive Analysis at first and then detected in 29 LUAD tissues and paired adjacent normal tissues using qRT-PCR. Results indicated that TINCR was evidently downregulated in LUAD. The association between TINCR and clinicopathological parameters was analyzed by Pearson's chi-square test, suggesting TINCR was closely correlated with TNM stage and lymph mode metastasis. Subsequently, the function role of TINCR was examined by gain- and loss-of-function studies in LUAD (A549 and NCI-H292) cells. As analyzed by the scratch wound-healing and transwell assays, results revealed that TINCR suppressed the migration and invasion of A549 and NCI-H292 cells. However, TINCR exerted no effects on the cell proliferation as determined by CCK8 assay. Furthermore, we reported that loss of Sp1 could inhibit TINCR expression. Expressions of miR-107/miR-1286 were detected by qRT-PCR assay in A549 and NCI-H292 cells after TINCR knockdown or overexpression. In addition, the direct binding ability of the predicted miR-107 or miR-1286 binding site on TINCR was validated by luciferase activity assay. Results indicated TINCR could constrain the expression of miR-107/miR-1286, and was a target of them in LUAD cells. Bioinformatics analyses showed that BTRC and RAB14 was the potential target gene of miR-107 and miR-1286, respectively. These data revealed a possible regulatory mechanism in which upregulation of TINCR induced by Sp1 could constrain the migration and invasion through regulating miR-107 or miR-1286 in LUAD cells. Conjointly, our findings provide a valuable insight into the regulatory mechanism of TINCR in LUAD, supportive to its potential of therapeutic target for LUAD patients.

Identification of plasma exosomes long non-coding RNA HAGLR and circulating tumor cells as potential prognosis biomarkers in non-small cell lung cancer.

BACKGROUND: The main purpose of this study was to identify the correlation between the expression of long non-coding RNA (lncRNA) HAGLR in plasma exosomes and the detection rate of circulating tumor cells (CTCs) in patients with non-small cell lung cancer (NSCLC). METHODS: LncRNA HAGLR expression was detected in plasma exosomes of 40 patients with NSCLC and 8 healthy subjects using qRT-PCR. CTCs were enriched and separated using CTC-BIOPSY® abnormal cell separator. The correlations between lncRNA HAGLR expression in plasma exosomes and CTCs of patients with NSCLC and clinical pathological parameters were also analyzed. Bioinformatics analyses indicated HAGLR was evidently down-regulated in NSCLC tissues when compared to normal controls. The relationship between differential expression of HAGLR with different stages of NSCLC and clinical prognosis were elucidated using corresponding statistical methods. RESULTS: HAGLR was significantly decreased in NSCLC, and there was obvious correlation with overall survival (P<0.05). CTCs were detected in peripheral blood of patients with NSCLC with the positive rate of 70.0%. In lung squamous cell carcinoma (LUSC), compared with the high expression group of HAGLR, the low expression group had a better overall survival (P<0.05). At the same time, the high expression of HAGLR was positively correlated with the high detection rate of CTCs (P<0.05), suggesting that the disease may have a later tumor stage, and poor prognosis. CONCLUSIONS: lncRNA HAGLR and CTCs could be used as potential biomarkers for NSCLC metastasis risk prediction.