Survival impact of gastrectomy and chemotherapy on gastric signet ring-cell carcinoma with different metastatic lesions: A population-based study.

BACKGROUND: A comprehensive understanding of gastric signet ring cell carcinoma (SRCC) is limited. The aim of our study was to analyze metastatic patterns of gastric SRCC and evaluate impacts of gastrectomy and chemotherapy for metastatic gastric SRCC. METHODS: We obtained data of gastric cancer patients between 2010 and 2017 in the Surveillance, Epidemiology, and End Results database. Chi-square tests were used to compare data significance. Kaplan-Meier, Cox proportional hazards regression and Fine-Gray competing risk analysis were used to analyze the difference in the overall survival (OS) and cancer-specific survival (CSS). Propensity-score matching was used to adjust numerical difference. RESULTS: Among 36,459 eligible gastric cancer patients, 6264 (17.2 %) were SRCC patients. Bone metastasis was more common in SRCC patients than in non-SRCC patients. The multivariate analysis showed that chemotherapy (HR = 0.30, 95 %CI = 0.27-0.33, p < 0.01) and gastrectomy (HR = 0.51, 95 %CI = 0.45-0.59, p < 0.01) were protective prognostic factors in certain stage Ⅳ SRCC patients. For the effect of gastrectomy, survival benefits could be found in patients with liver metastasis. The gastrectomy was not associated with improved OS in patients with lung or multiple metastases. In subgroup analysis, SRCC patients with metastasis who received gastrectomy and chemotherapy (HR = 0.17, p < 0.01; HR = 0.03, p < 0.01) had a better OS and CSS than those who had chemotherapy only (HR = 0.30, p < 0.01; HR = 0.18, p < 0.01). CONCLUSION: Our study analyzed the unique metastatic patterns of gastric SRCC and recommended chemotherapy as the first choice in metastatic SRCC. For patients with liver metastasis, gastrectomy plus chemotherapy can be considered.

The combination of preoperative fibrinogen-to-albumin ratio and postoperative TNM stage (FAR-TNM) predicts the survival in gastric cancer patients after gastrectomy.

OBJECTIVE: There are many factors that affect the survival of patients with gastric cancer, such as TNM stage, the patient's nutritional status, inflammation, and so on. In this study, the prognostic significance of preoperative fibrinogen-to-albumin ratio (FAR) and postoperative TNM staging in patients with gastric cancer was retrospectively studied. METHODS: A total of 265 patients (surgery dates from January 2007 to December 2013) were included in this retrospective study. All the patients were confirmed by pathology after operation. Categorical variables were compared using the χ2 test. Kaplan-Meier and log-rank tests were used for survival analysis. Cox proportional hazard models were used to assess prognostic factors. Nomogram was applied to predict the prognosis of overall survival (OS). RESULTS: The higher the FAR value, the more lymph node metastasis, the later the TNM stage, and the shorter the survival time. We established a new scoring system, the FAR-TNM score, which combined FAR and TNM stage. The FAR-TNM score was significantly related to tumor location, tumor size, Bormann types, differentiation, operative type, vascular invasion, nerve invasion, depth of invasion, lymphatic metastasis, and advanced TNM stage. Multivariate Cox regression analysis demonstrated that tumor location, TNM stage, adjuvant chemotherapy, and FAR-TNM score were independent prognostic elements for OS in patients with GC. CONCLUSIONS: The FAR-TNM score was a valuable independent prognostic indicator for GC patients after surgery, which can help clinicians to assist the treatment and long-term management of patients with gastric cancer.

Prognostic significance of platelet-to-lymphocyte ratio (PLR) in patients with breast cancer treated with neoadjuvant chemotherapy: a meta-analysis.

OBJECTIVE: Platelet-to-lymphocyte ratio (PLR), known as a key systemic inflammatory parameter, has been proved to be associated with response to neoadjuvant therapy in breast cancer (BC); however, the results remain controversial. This meta-analysis was carried out to evaluate the prognostic values of PLR in patients with BC treated with neoadjuvant chemotherapy (NACT). DESIGN: Meta-analysis. DATA SOURCES: Relevant literature published on the following databases: PubMed, Embase, Web of Science databases and the Cochrane Library. ELIGIBILITY CRITERIA: All studies involving patients with BC treated with NACT and peripheral blood pretreatment PLR recorded were included. DATA EXTRACTION AND SYNTHESIS: Two researchers independently extracted and evaluated HR/OR and its 95% CI of survival outcomes, pathological complete response (pCR) rate and clinicopathological parameters. RESULTS: The last search was updated to 31 December 2022. A total of 22 studies with 5533 patients with BC treated with NACT were enrolled in the final meta-analysis. Our results demonstrate that elevated PLR value appears to correlate with low pCR rate (HR 0.77, 95% CI 0.67 to 0.88, p<0.001, I2=75.80%, Ph<0.001) and poor prognosis, including overall survival (OS) (HR 1.90, 95% CI 1.39 to 2.59, p<0.001; I2=7.40%, Ph=0.365) and disease-free survival (HR 1.97, 95% CI 1.56 to 2.50, p<0.001; I2=0.0%, Ph=0.460). Furthermore, PLR level was associated with age (OR 0.86, 95% CI 0.79 to 0.93, p<0.001, I2=40.60%, Ph=0.096), menopausal status (OR 0.83, 95% CI 0.76 to 0.90, p<0.001, I2=50.80%, Ph=0.087) and T stage (OR 1.05, 95% CI 1.00 to 1.11, p=0.035; I2=70.30%, Ph=0.005) of patients with BC. CONCLUSIONS: This meta-analysis demonstrated that high PLR was significantly related to the low pCR rate, poor OS and disease-free survival (DFS) of patients with BC treated with NACT. Therefore, PLR can be used as a potential predictor biomarker for the efficacy of NACT in BC.

Over-Expression of ARID3B Suppresses Tumor Progression and Predicts Better Prognosis in Patients With Gastric Cancer.

BACKGROUND: ARID3B (AT-rich interaction domain 3B) has been demonstrated to be associated with the progression and patient prognosis of several human tumors. We conducted the present study to investigate the biological behavior and clinical relevance of ARID3B in gastric cancer (GC). METHODS: Detection of the expression level in GC tissues and cell lines were performed by Western blot and immunohistochemistry. We also retrospectively analyzed the correlation of ARID3B with clinicopathological characteristics and patient prognosis in gastric cancer. The biological functions of ARID3B in GC cells were further explored by transwell migration assays, wound healing assays and cell proliferation assay. RESULTS: The present study suggested that the expression of ARID3B was significantly lower in GC tissues than in adjacent normal tissues. IHC staining in tissues of 406 GC patients from training and validation sets verified that ARID3B over-expression correlated with clinicopathological features, such as degree of differentiation and clinical stage. Meanwhile, ARID3B was proved to be an independent prognostic factor for GC prognosis. Furthermore, over-expression of ARID3B suppressed proliferation in GC cells according CCK8 assay. We found that over-expression of ARID3B inhibited GC cell migration by transwell assay and wound healing assay. Furthermore, EMT markers were detected in ARID3B over-expression GC cells, which showed that ARID3B may inhibit metastasis of GC cells. CONCLUSION: Our results firstly revealed that the expression level of ARID3B was closely correlated with clinicopathological features and may serve as an independent prognostic factor for GC patients. More importantly, ARID3B could suppress GC progression, including cell proliferation, migration and metastasis.

A pan-cancer analysis of the oncogenic role of dual-specificity tyrosine (Y)-phosphorylation- regulated kinase 2 (DYRK2) in human tumors.

Although there have been studies correlating DYRK2 with a number of human cancers, there has been no pan-cancer analysis. Therefore, through the TCGA database, we conducted a related study on the expression of DYRK2 in cancers.The expression of DYRK2 is obviously increased in some cancers, while the opposite is true in others, and there is a clear association between its expression and the prognosis of cancer patients.The mutation of DYRK2 is also significantly correlated with patients' prognosis in certain human tumors. In addition, phosphorylation and methylation levels of DYRK2 are different between tumor tissues and adjacent normal tissues in various tumors. In the tumour microenvironment, the expression of DYRK2 correlates with cancer-associated fibroblast infiltration, such as BLCA or HNSC. In order to fully understand the role of DYRK2 in different tumors, we conducted a pan-cancer analysis.

Cancer-associated fibroblast-released extracellular vesicles carrying miR-199a-5p induces the progression of​ gastric cancer through regulation of FKBP5-mediated AKT1/mTORC1 signaling pathway.

Accumulating evidence has unfolded the significance of extracellular vesicles (EVs) in diseases and cancers. Here, we attempted to discuss the role of cancer-associated fibroblasts (CAFs)-derived EVs containing miR-199a-5p in gastric tumorigenesis. Upregulated miR-199a-5p was first identified in cancer cells. Then, we selected CAFs for isolation of EVs which were co-cultured with AGS cells. We observed successful delivery of miR-199a-5p via CAF-derived EVs. Besides, miR-199a-5p promoted malignant properties of AGS cells. Moreover, miR-199a-5p downregulated FKBP5, leading to upregulated phosphorylation level of AKT1, which promoted the malignant phenotypes of AGS cells by activating mammalian target of rapamycin complex 1(mTORC1). Exosomal miR-199a-5p from CAFs promoted gastric tumorigenesis in vivo. Our findings point toward the critical role of CAFs-derived EVs carrying miR-199a-5p in gastric cancer progression.

Clinical Significance of Serum Biomarkers in Stage IV Non-Small-Cell Lung Cancer Treated with PD-1 Inhibitors: LIPI Score, NLR, dNLR, LMR, and PAB.

Background: To assess the prognostic value of pretreatment serum biomarkers in stage IV non-small-cell lung cancer (NSCLC) patients treated with PD-1 (programmed cell death protein 1) inhibitors and their value as a predictor of benefit. Methods: We performed a retrospective study including patients with stage IV NSCLC who were treated with anti-PD-1 drugs in first or advanced lines of therapy in the Affiliated Tumor Hospital of Nantong University. Serum biomarkers such as NLR, dNLR, LMR, PAB, ALB, and LIPI scores were calculated and analyzed in detail. Results: A total of 85 patients with stage IV NSCLC treated with PD-1 inhibitors in the first or advanced lines of therapy were included in this subject. According to the tumor response of PD-1-based treatment, ORR was 42.4% (36/85) and DCR was 68.2% (58/85). The median OS and PFS were 20.0 months and 7.0 months, respectively. The ROC curves showed that the serum biomarkers of NLR, dNLR, LDH, LMR, PAB, and ALB were significantly associated with overall survival and helped to determine the cut-off value. The multivariate Cox proportional hazard analyses for stage IV NSCLC patients treated with PD-1 inhibitors indicated that dNLR (P < 0.001) and ALB (P = 0.033) were independent prognostic indicators of PFS, while liver metastasis (P = 0.01), NLR (P = 0.01), dNLR (P = 0.001), and LMR (P = 0.006) were independent prognostic indicators of OS. Moreover, patients of the good LIPI group showed prolonged PFS and OS than those with intermediate/poor LIPI score (P < 0.001 and P = 0.006, respectively). Conclusions: Pretreatment dNLR is an independent prognostic indicator of both PFS and OS in stage IV NSCLC patients treated with PD-1 inhibitors. Pretreatment LIPI, combining dNLR > 3 and LDH>ULN, was correlated with worse outcome for stage IV NSCLC patients treated with ICI. High NLR, high dNLR, low LMR, and low ALB at baseline might be useful as an early predictive biomarker of benefit.

Prognostic Value of the Combination of HB (hemoglobin) and CEA in Resectable Gastric Cancer.

Objective: In order to investigate the prognostic value of a novel biomarker combining serum carcinoembryonic antigen (CEA) and hemoglobin (HB) levels in patients with resectable gastric cancer. Introduction: This retrospective study assessed the relationship between CEA, hemoglobin levels, a novel combined prognostic biomarker (HB-CEA) and clinicopathological features of gastric cancer. Their prognostic values in gastric cancer were also analyzed. Materials and Methods: This retrospective study evaluated the CEA, hemoglobin levels and clinicopathological features of patients with resectable gastric cancer. Kaplan-Meier curves, univariate and multivariate Cox proportional models were used to determine the prognostic significance of these factors for overall survival (OS) in the training and validation sets (n=353 and n=388, respectively). Based on optimal cutoff values of CEA and hemoglobin (3.395 ng/mL and 125.5 g/L, respectively), patients were stratified into three groups: HB-CEA=0, 1, and 2 (CEA <3.395 ng/mL and HB ≥125.5 g/L; CEA ≥3.395 ng/mL or HB <125.5 g/L; and CEA ≥3.395 ng/mL and HB <125.5 g/L, respectively). Results: The area under the curve was larger for HB-CEA than for either HB or CEA alone (training set: 0.677, 0.650, and 0.629; validation set: 0.670, 0.605, and 0.605, respectively). HB-CEA was strongly associated with age, tumor size, differentiation, pathological TNM stage (pTNM), depth of tumor invasion, lymph node metastasis, and survival status (all p<0.05). A higher HB-CEA score correlated with poor survival (Kaplan-Meier curves, all p<0.05). Multivariate analysis showed that HB-CEA was an independent prognostic factor for OS (p<0.05). Conclusion: Preoperative HB-CEA, as a potential novel hematological biomarker, can predict the progression of gastric cancer and the prognosis of patients, and is of great value in guiding clinical practice. Therefore, patients with a higher HB-CEA score should receive more extensive follow-up for early detection and intervention of tumor progression.

Monitoring early dynamic changes of plasma cell-free DNA and pretreatment pre-albumin to predict chemotherapy effectiveness and survival outcomes in advanced non-small cell lung cancer.

Background: This study aimed to determine whether plasma cell-free DNA (cfDNA) and pretreatment parameters provide useful therapeutic response and prognostic information for advanced non-small cell lung cancer (NSCLC) patients. Methods: A total of 114 patients with advanced NSCLC who underwent systemic chemotherapy were included in this study. Detection of plasma cfDNA concentration and blood parameters before and at the sixth week after treatment was performed. The prognostic value of cfDNA dynamic changes and laboratory parameters was determined via a receiver operating characteristic (ROC) curve, and then analyzed by comparing with the therapeutic efficacy and progression-free survival (PFS). Based on the ROC curve, it revealed a pretreatment pre-albumin (PA) concentration of 21.7 mg/dL was the cut-off value. The Cox proportional hazards regression model was used to evaluate the predictive factors for treatment response and PFS via univariate and multivariate analyses. Results: Patients with cfDNA reduction ≥20% at the sixth week after treatment reported a significantly better disease control rate (DCR) and prolonged PFS (median PFS: 10.0 vs. 4.0 months, P<0.001). The median PFS of low PA group (PA <21.7 mg/dL) was 6.0 months, while the median PFS of high PA group (PA ≥21.7 mg/dL) was 8.0 months. The combined assessment of cfDNA and pretreatment pre-albumin was associated with significantly better survival outcomes compared with the remaining population (P<0.001). Multivariate analysis for DCR indicated that cfDNA reduction ≥20% was an independent factor (OR =0.419, P=0.001). In addition, multivariate analysis identified 6 significant factors associated with PFS: cfDNA reduction of ≥20%, age <65 years, Eastern Cooperative Oncology Group (ECOG) score ≥2, driver gene mutation, chemotherapy combined regimen, and treatment response of complete response (CR) and partial response (PR). The nomogram could predict the 2-year PFS probability of advanced NSCLC patients after treatment, and the C-index was 0.817. Conclusions: Monitoring cfDNA changes and pretreatment pre-albumin level in advanced NSCLC patients receiving treatment is an accurate predictor of tumor response and PFS. Combined assessment of cfDNA and pretreatment pre-albumin is helpful for predicting survival outcomes. These findings may assist in identifying high-risk patients and guiding treatment strategies.

Downregulation of promoter methylation gene PRDM5 contributes to the development of tumor proliferation and predicts poor prognosis in gastric cancer.

Background: Epigenetic aberrations of tumor suppressor genes (TSGs), particularly DNA methylation, are frequently involved in the pathogenesis of gastric cancer (GC). Previous studies have shown that PRDM5 is methylated and silenced in GC. However, the role of PRDM5 in GC progression has not been explored. Methods: The expression and epigenetic alterations of PRDM5 in GC were analyzed in public datasets. The mRNA and protein expression of PRDM5 in fresh tissues were detected by semi-quantitative PCR and Western blot. And expression of PRDM5 in gastric paracarcinoma and carcinoma tissues from 162 patients was detected by immunohistochemistry (IHC) and assessed the association with different clinicopathological features. The prognostic value of PRDM5 in GC patients was evaluated using Kaplan-Meier plotter. We also studied promoter region methylation of PRDM5 in GC by methylation-specific PCR (MSP). The effects of PRDM5 on cell proliferation and migration were conducted by functional experiments in vitro. Results: The expression of PRDM5 was downregulated in GC, and that was associated with poor survival and tumor progression. And PRDM5 expression was found to be an independent prognostic factor for GC. We also found that the methylation of PRDM5 promoter was closely related to the histopathological types and the progression of tumors through the public relations database. In vitro, ectopical expression of PRDM5 inhibited the growth of tumor cells, while knockdown of PRDM5 increased the proliferation and migration of tumor cells. Conclusion: These results suggest that PRDM5 may be a novel TSG methylated in GC that plays important roles in GC development. And we found PRDM5 as a potential survival biomarker for GC, especially in well differentiated GC. PRDM5 expression was significantly correlated with tumor stage and histological type.

Enhanced expression of FGF19 predicts poor prognosis in patients with non-small cell lung cancer.

BACKGROUND: Lung cancer is one of the most common cancers and a leading cause of cancer-related death worldwide. Although many treatment options exist for lung cancer, some patients still suffer postoperative recurrence, and a consequent reduction of overall survival (OS). Our study aimed to investigate the correlation of FGF19 expression with the clinicopathological features and survival outcomes of non-small cell lung cancer (NSCLC) patients. METHODS: Bioinformatics analysis was conducted using the data from The Cancer Genome Atlas (TCGA) database to distinguish between the FGF19 levels of tumor and normal tissue and to determine their correlation with the OS. A total of 187 NSCLC patients who underwent radical resection of lung cancer were enrolled, and tissues were collected to determine FGF19 expression by immunohistochemistry (IHC) assay. Clinicopathological features including the survival date were collected for detailed research. RESULTS: According to the analysis based on the TCGA database, we found that the NSCLC tissues exhibited enhanced FGF19 messenger RNA (mRNA) expression and that the FGF19 mRNA levels correlated with shorter OS in NSCLC patients. IHC staining indicated that 88 (47.1%) patients had high FGF19 expression and 99 (52.9%) patients had low FGF19 expression. Meanwhile, survival data showed that high FGF19 expression was correlated with reduced OS (P<0.001). Moreover, both the univariate analysis and the forward stepwise multivariate Cox regression revealed that high FGF19 expression was an independent prognostic factor for decreased OS (P=0.001). CONCLUSIONS: The expression of FGF19 is significantly upregulated in NSCLC, and the overexpression of FGF19 is correlated with poor OS, especially in lung adenocarcinoma (LUAD) cases. FGF19 might serve as a potential biomarker for predicting poor OS in NSCLC patients.

The Role of miR-4256/HOXC8 Signaling Axis in the Gastric Cancer Progression: Evidence From lncRNA-miRNA-mRNA Network Analysis.

Gastric cancer is a deadly human malignancy and the molecular mechanisms underlying gastric cancer pathophysiology are very complicated. Thus, further investigations are warranted to decipher the underlying molecular mechanisms. With the development of high-throughput screening and bioinformatics, gene expression profiles with large scale have been performed in gastric cancer. In the present study, we mined The Cancer Genome Atlas (TCGA) database and analyzed the gene expression profiles between gastric cancer tissues and normal gastric tissues. A series of differentially expressed lncRNAs, miRNAs and mRNAs between gastric cancer tissues and normal gastric tissues were identified. Based on the differentially expressed genes, we constructed miRNA-mRNA network, lncRNA-mRNA network and transcriptional factors-mRNA-miRNA-lncRNA network. Furthermore, the Kaplan survival analysis showed that high expression levels of EVX1, GBX2, GCM1, HOXC8, HOXC9, HOXC10, HOXC11, HOXC12 and HOXC13 were all significantly correlated with shorter overall survival of the patients with gastric cancer. On the other hand, low expression level of HOXA13 was associated with shorter overall survival of patients with gastric cancer. Among these hub genes, we performed the in vitro functional studies of HOXC8 in the gastric cancer cells. Knockdown of HOXC8 and overexpression of miR-4256 both significantly repressed the gastric cancer cell proliferation and migration, and miR-4256 repressed the expression of HOXC8 via targeting its 3' untranslated region in gastric cancer cells. Collectively, our results revealed that a complex interaction networks of differentially expressed genes in gastric cancer, and further functional studies indicated that miR-4256/HOXC8 may be an important axis in regulating gastric cancer progression.

Prognostic Value of the Pretreatment Systemic Immune-Inflammation Index in Patients with Colorectal Cancer.

BACKGROUND: Multiple studies have reported the significance of the systemic immune-inflammation index (SII) in the prognosis of colorectal cancer (CRC), but no consensus has yet been reached. The purpose of this study was to systematically assess the prognostic value of SII in patients with CRC. MATERIALS AND METHODS: We performed a systematic literature search in PubMed, Embase, and the Cochrane Library for eligible studies. The correlation between pretreatment SII and overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) in CRC patients was evaluated by combining the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Twelve studies involving 3919 patients were included. Comprehensive analysis results showed that high SII indicated poor OS in CRC patients (HR = 1.777, 95% CI: 1.328-2.376). Compared with patients with low SII values, patients with high SII had lower PFS (HR = 1.658, 95% CI: 1.189-2.311). Subgroup analysis further verified the above results. CONCLUSIONS: SII may be a noninvasive and powerful tool for predicting survival outcomes in CRC patients. However, more well-designed studies are needed to validate our findings.

Prognostic and clinicopathological significance of pretreatment mean platelet volume in cancer: a meta-analysis.

OBJECTIVE: Our study aimed to evaluate the prognostic and clinicopathological significance of pretreatment mean platelet volume (MPV) on cancer by using meta-analysis of published studies. DESIGN: Meta-analysis. DATA SOURCES: Relevant studies available before 22 December 2019 were identified by searching MEDLINE, EMBASE. ELIGIBILITY CRITERIA: All published studies that assessed the prognostic and clinicopathological significance of pretreatment MPV on cancer were included. DATA EXTRACTION AND SYNTHESIS: Studies were identified and extracted by two reviewers independently. The HR/OR and its 95% CIs of survival outcomes and clinicopathological parameters were calculated. RESULTS: A total of 38 eligible studies (41 subsets) with 9894 patients with cancer were included in the final meta-analysis. MPV level was not significantly associated with both overall survival (HR 0.98, 95% CI 0.84 to 1.14) and disease-free survival (HR 1.22, 95% CI 0.86 to 1.73) of patients with cancer. Neither advanced nor mixed-stage tumour patients showed significant association between MPV and overall survival (HR 1.36, 95% CI 0.96 to 1.94, HR 0.90, 95% CI 0.74 to 1.09). However, high MPV had the strongest relationship with poor overall survival (HR 2.01; 95% CI 1.08 to 3.41) in gastric cancer, followed by pancreatic cancer (HR 1.54; 95% CI 1.31 to 1.82). Whereas in the subgroup using receiver operating characteristic curve method to define cut-off values, low MPV was significantly related to poor overall survival (HR 0.78, 95% CI 0.64 to 0.95). In addition, MPV had no significant association with age (OR 0.96, 95% CI 0.90 to 1.02), sex (OR 1.04, 95% CI 1.00 to 1.09), depth of cancer invasion (OR 0.90, 95% CI 0.77 to 1.04) and tumour stage (OR 0.91, 95% CI 0.78 to 1.07). CONCLUSIONS: Pretreatment MPV level is of no clearly prognostic significance in cancers and no significant association with clinicopathological parameters of patients with cancers.

Combining the Fibrinogen-to-Pre-Albumin Ratio and Prognostic Nutritional Index (FPR-PNI) Predicts the Survival in Elderly Gastric Cancer Patients After Gastrectomy.

BACKGROUND: Inflammation and nutrition are important causes contributing to the progression and poor survival of gastric cancer (GC). The objective of this study is to investigate the prognostic significance of the preoperative fibrinogen-to-pre-albumin ratio (FPR) and the prognostic nutritional index (PNI) in GC patients who have undergone gastrectomy. METHODS: A total of 274 patients with resected pathological GC from January 2007 to December 2013 were enrolled in this retrospective study. Survival analysis was performed using Kaplan-Meier and log rank tests. Univariate and multivariate analyses were established to identify independent prognostic factors of 5-year survival. A predictive nomogram was used to predict prognosis of overall survival (OS), and its accuracy was determined by Harrell's concordance index (C index). RESULTS: A high preoperative FPR-PNI score was significantly correlated with age, bigger tumor size, more lymphatic metastases and advanced TNM stage. Univariate analysis revealed that the GC patients with high FPR, low PNI and high FPR-PNI scores had shorter survival time. Multivariate analysis showed that FPR-PNI was an independent prognostic factor for OS in GC patients, especially in elderly patients. In the sub-analysis by age, the FPR-PNI score could significantly increase the accuracy of prognosis compared with the FPR and PNI alone in elderly GC patients. CONCLUSION: The preoperative FPR-PNI score is an effective independent prognostic index for GC patients after surgery, especially in elderly patients.

Clinicopathological and prognostic significance of platelet-lymphocyte ratio (PLR) in gastric cancer: an updated meta-analysis.

BACKGROUND: Pre-treatment PLR (platelet-lymphocyte ratio) was reported to be associated with the prognosis in gastric cancer (GC), but the results remain inconclusive. This meta-analysis aimed to investigate the prognostic potential of the pre-treatment PLR in gastric cancer. METHODS: We performed a systematic literature search in PubMed, Embase, and the Cochrane Library to identify eligible publications. The hazard ratio (HR)/odds ratio (OR) and its 95% confidence (CI) of survival outcomes and clinicopathological parameters were calculated. RESULTS: A total of 49 studies (51 cohorts), collecting data from 28,929 GC patients, were included in the final analysis. The pooled results demonstrated that the elevated pre-treatment PLR was significantly associated with poor overall survival (OS) (HR 1.37, 95% CI 1.26-1.49, p < 0.001; I2 = 79.90%, Ph < 0.001) and disease-free survival (DFS) (HR 1.52, 95% CI 1.22-1.90, p < 0.001, I2 = 88.6%, Ph < 0.001). Furthermore, the patients with the elevated PLR had a higher risk of lymph node metastasis (OR = 1.17, 95% CI 1.02-1.33, p = 0.023), serosal invasion (T3+T4) (OR = 1.34, 95% CI 1.10-1.64, p = 0.003), and increased advanced stage (III+IV) (OR = 1.20, 95% CI 1.06-1.37, p = 0.004). CONCLUSIONS: An elevated pre-treatment PLR was a prognostic factor for poor OS and DFS and associated with poor clinicopathological parameters in GC patients.

Long noncoding RNA ANRIL promotes the malignant progression of cholangiocarcinoma by epigenetically repressing ERRFI1 expression.

Long noncoding RNAs (lncRNAs) have recently been verified to have significant regulatory functions in many types of human cancers. The lncRNA ANRIL is transcribed from the INK4b-ARF-INK4a gene cluster in the opposite direction. Whether ANRIL can act as an oncogenic molecule in cholangiocarcinoma (CCA) remains unknown. Our data show that ANRIL knockdown greatly inhibited CCA cell proliferation and migration in vitro and in vivo. According to the results of RNA sequencing analysis, ANRIL knockdown dramatically altered target genes associated with the cell cycle, cell proliferation, and apoptosis. By binding to a component of the epigenetic modification complex enhancer of zeste homolog 2 (EZH2), ANRIL could maintain lysine residue 27 of histone 3 (H3K27me3) levels in the promoter of ERBB receptor feedback inhibitor 1 (ERRFI1), which is a tumor suppressor gene in CCA. In this way, ERRFI1 expression was suppressed in CCA cells. These data verified the key role of the epigenetic regulation of ANRIL in CCA oncogenesis and indicate its potential as a target for CCA intervention.

Comprehensive analysis of differentially expressed lncRNAs as diagnostic and prognostic markers for colorectal cancer.

Colorectal cancer (CRC) is the third most common type of cancer worldwide. Recent studies had revealed the important roles of long non-coding RNAs (lncRNAs) in a variety of human cancers, including CRC. However, the molecular mechanisms associated with CRC remain largely undetermined. In the current study, the GSE21510 dataset was analyzed to identify differentially expressed mRNAs and lncRNAs in CRC samples. The Database for Annotation, Visualization and Integrated Discovery was used to perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway bioinformatics analysis. Furthermore, protein-protein interaction networks were constructed to reveal interactions among differentially expressed proteins. Kaplan-Meier analysis was subsequently performed to determine the association between key lncRNA expression and the overall survival of patients with CRC. A total of 107 upregulated lncRNAs and 43 downregulated lncRNAs were identified in CRC. A lncRNA mediated co-expression network was also constructed in CRC. Bioinformatics analysis indicated that lncRNAs were associated with a series of biological processes, including 'xenobiotic glucuronidation', 'rRNA processing', 'sister chromatid cohesion', 'cell proliferation', 'mitotic nuclear division' and 'cell cycle regulation'. Furthermore, a higher expression of small nucleolar RNA host gene 17, tetratricopeptide repeat domain 2B-antisense RNA (AS) 1, erythrocyte membrane protein band 4.1 like 4A-AS2, deleted in lymphocytic leukemia 2, and a lower expression of muscle blind like splicing regulator 1-AS1 and LOC389332 were associated with shorter overall survival time in CRC samples. The present study provides useful information that can be used in the identification of novel biomarkers for CRC.

Low expression of PDHA1 predicts poor prognosis in gastric cancer.

PDH E1 component subunit alpha (PDHA1) has been reported to be biologically significant in several human tumors. The aim of this study was to investigate the expression of PDHA1 in gastric cancer (GC) and its relationship with clinicopathological characteristics and prognosis. Oncomine analysis of neoplastic vs. normal tissue showed that the mRNA levels of PDHA1 were significantly underexpressed in different types of GC across three analyses. Underexpression of PDHA1 was found in intestinal-type GC (P = 0.009), diffuse-type GC (P = 0.036), and mixed-type GC (P = 0.025). Immunohistochemical staining of the 174 GC tissue microarray showed that PDHA1 staining is much stronger in normal mucosa than in GC samples (P = 0.040). Furthermore, PDHA1 expression levels were found to be significantly lower in 69.05% (87/126) of poorly differentiated GCs as compared to the well or moderately differentiated ones (P = 0.037). Intriguingly, PDHA1 expression was significantly correlated with depth of invasion (P < 0.001), lymph node metastasis (P < 0.001), TNM stage (P < 0.001), and nerve invasion (P = 0.006). However, it was not correlated with gender, age, Lauren classification, and lymphovascular invasion (P > 0.05 for all). Kaplan-Meier analysis revealed that low tumor expression of PDHA1 was significantly correlated with a poorer overall survival in patients with GC (5-year overall survival rates for patients with low vs high PDHA1 expression = 49.8% vs 72.7%, hazard ratio of death from GC = 2.594, 95% CI = 1.527 to 4.408, P < 0.001). Multivariate analysis showed that PDHA1 (P = 0.025) was an independent predictor of overall survival. These findings are of potential clinical utility and merit further validation.

Endoplasmic reticulum chaperone glucose-regulated protein 78 in gastric cancer: An emerging biomarker.

The endoplasmic reticulum (ER) is the principal organelle responsible for the synthesis, initial post-translational modification, folding, export and secretion of proteins. It is also responsible for the maintenance of cellular homeostasis. In response to cellular stress conditions including glucose deprivation, hypoxia and changes in calcium homeostasis, ER stress machinery is activated and triggers the unfolded protein response, resulting in the restoration of homeostasis or activation of cell death. Glucose-regulated protein 78 (GRP78), a molecular chaperone, may be induced by ER stress at the transcriptional and translational level. A number of studies have demonstrated that GRP78 serves an important role in tumor cell proliferation, metastasis, angiogenesis and drug-resistance. The present review systematically describes the association between GRP78 expression and gastric cancer pathogenesis, and emphasizes that GRP78 is a novel diagnostic and therapeutic biomarker of gastric cancer.