International Journal of Biological Markers最新文献

Background: Irradiation, which affects cytokine secretion, is used to treat cancer patients. Cytokine levels have correlations to disease parameters, serving as biomarkers for patients. We aim to explore the effect of irradiation on cytokine production both in vitro (using lymphocytes from healthy donors) and in vivo (using serum levels of head and neck cancer patients following irradiation) and correlating them to mucositis severity/need for percutaneous endoscopic gastroscopy (PEG) tube installation.

Methods: Cytokine production by cultured lymphocytes from healthy donors, in vitro, following irradiation of 5 or 10 Gy. In addition, blood from 23 patients with head and neck cancers, irradiated by 60-72G in vivo, were assessed for inflammatory cytokines (tumor necrosis factor (TNF)α, interleukin (IL)-6, IL-8, IL-18), the anti-inflammatory cytokine IL-10, and the general marker sIL-2R. Following radiation, selected patients who were developing mucositis were treated by PEG tube installation. Changes in cytokine levels were studied as predictive biomarkers of response to therapy/PEG tube installation. Cytokine production levels were measured using ELISAs kits.

Results: Irradiation decreased the levels of all tested cytokines, most notably IL-6 and IL-8, proportional to irradiation dose. In patients, increases in cytokine levels, correlated with mucositis severity and potentially the need for PEG tube installation.

Conclusions: Irradiation decreased the levels of all cytokines of healthy lymphocytes in a dose-dependent manner, especially those of IL-6 and IL-8. This study shows a correlation between high and increasing levels of inflammatory cytokines, sIL-2R, plus radiation toxicity and the need for PEG. The reduction of cytokine levels after radiotherapy predicts that PEG will not be required. Thus, our study shows that cytokine changes are predictive biomarkers in head and neck cancer patients.

The association of platelet-to-lymphocyte ratio (PLR) with the clinicopathological features and prognosis in patients with breast cancer was evaluated. Related studies were searched from PubMed, Embase, Cochrane Library, and Web of Science up to July 1, 2021. Then, basic characteristic and prognostic data were extracted from the included studies. We synthesized and compared primary outcomes such as overall survival. Subgroups analyses in pathology, geographical area, follow-up time, and sample size were conducted. The pooled hazard ratio (HR), odds ratio (OR), and 95% confidence interval (CI) served as measures to assess the relationship of PLR with prognosis and clinicopathological features of breast cancer patients. After literature retrieval and selection, 20 studies with 7484 patients were included in this meta-analysis. High PLR was significantly related to poor overall survival (HR = 1.88; 95% CI 1.61, 2.19; P < 0.001) in breast cancer patients. Also, high PLR was associated with lymph node metastasis (LNM) (OR = 1.82; 95% CI 1.32, 2.52; P < 0.001), advanced tumor-node-metastasis (TNM) stage (OR = 1.89; 95% CI 1.25, 2.87; P = 0.003), and distant metastasis (OR = 1.76; 95% CI 1.14, 2.72; P = 0.01) in breast cancer. The stability and reliability of results in this meta-analysis were confirmed by sensitivity analysis. Elevated PLR is related to a poor prognosis and a higher risk of LNM, advanced TNM stage, and distant metastasis in breast cancer patients. Therefore, PLR can be identified as a biomarker with potential prognostic value in breast cancer.

Purpose: There are conflicting opinions on whether miR-486 could be used for cancer diagnosis and prognosis. Therefore, this present study investigated the potential effect of miR-486 on lung cancer diagnosis and prognosis.

Methods: We researched PubMed, Embase, Wanfang and Chinese National Knowledge Infrastructure databases to select relevant publications. Specificity and sensitivity were obtained for the pooled and subgroup diagnostic meta-analysis while the hazard ratio was for prognostic meta-analysis. Publication analyses and sensitivity analyses were conducted to investigate possible sources of heterogeneity.

Results: The overall sensitivity and specificity with 95% confidence intervals were 0.8 (0.8-0.9) and 0.9 (0.9-0.9). Results of subgroup analysis showed that high diagnostic efficacy might be obtained by miR-486 combined with other microRNAs (area under the curve (AUC): 0.9 (0.9-1.0)) to distinguish lung cancer patients from healthy controls (AUC: 1.0 (0.9-1.0)), especially for lung adenocarcinoma (AUC: 1.0 (1.0-1.0)) in the Asian population (AUC: 0.9 (0.9-1.0)). For prognosis prediction of miR-486 in overall non-small cell lung cancer, the overall hazard ratio with 95% confidence interval was 1.15 (0.85-1.54) for high versus low expression of miR-486, which indicated that a high miR-486 level was not related to the high risk of poor outcome. However, for the subgroup of progression-free survival and patients with chemotherapy, the hazard ratio was 0.41 (0.21-0.77), indicating that the higher miR-486 level would decrease the risk of poor progression-free survival for lung cancer patients with chemotherapy.

Conclusion: This study suggested circulating miR-486 combined with other microRNAs could be used as ideal biomarkers in early diagnosis and prognosis prediction for lung cancer, especially for lung adenocarcinoma in the Asian population.

Background: Invasive ductal carcinoma (IDC) is the most common type of breast cancer so its early detection can lead to a significant decrease in mortality rate. However, prognostic factors for IDC are not adequate and we need novel markers for the treatment of different individuals. Although positron emission tomography and magnetic resonance imaging techniques are available, they are based on morphological features that do not provide any clue for molecular events accompanying cancer progression. In recent years, "omics" approaches have been extensively developed to propose novel molecular signatures of cancers as putative biomarkers, especially in biofluids. Therefore, a mass spectrometry-based metabolomics investigation was performed to find some putative metabolite markers of IDC and potential metabolites with prognostic value related to the estrogen receptor, progesterone receptor, lymphovascular invasion, and human epidermal growth factor receptor 2.

Methods: An untargeted metabolomics study of IDC patients was performed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The multivariate principal component analysis by XCMS online built a model that could separate the study groups and define the significantly altered m/z parameters. The most important biological pathways were also identified by pathway enrichment analysis.

Results: The results showed that the significantly altered metabolites in IDC serum samples mostly belonged to amino acids and lipids. The most important involved pathways included arginine and proline metabolism, glycerophospholipid metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis.

Conclusions: Significantly altered metabolites in IDC serum samples compared to healthy controls could lead to the development of metabolite-based potential biomarkers after confirmation with other methods and in large cohorts.

Overall survival of non-small cell lung cancer (NSCLC) patients remains disappointingly low. The estrogen receptor (ER) was considered a promising therapeutic target for NSCLC. Numerous studies have linked expression of ERβ to lung cancer outcome. However, results are conflicting regarding the association of ERβ with surviving lung cancer. The aim of this meta-analysis was to evaluate the prognostic aspect of ERβ expression on survival among NSCLC patients. We performed a final analysis of prognostic value of overexpression ERβ on 3500 patients from 18 evaluable studies (from January 1, 2000 to May 1, 2021). The reference category is specified as low ERβ expression levels. Summarized hazard ratios were calculated. Our study showed that the pooled hazard ratios of ERβ overexpression for overall survival in NSCLC was 0.81 (95% confidence interval (CI): 0.64-1.02, P = 0.07) by univariate analysis and 1.06 (95% CI: 0.83-1.36, P = 0.63) by multivariate analysis. Pooled hazard ratio by univariate analysis in Asian studies was 0.73 (95%CI: 0.59-0.89, P = 0.002). Pooled hazard ratio by univariate analysis was 0.75 (95% CI: 0.61-0.93, P = 0.009) from seven studies reported for nuclear ERβ. No significant results were found in subgroups by multivariate analysis. No significant results were found in studies outside Asia or in studies reported for cytoplasmic ERβ. Our results suggested that expression of ERβ might not be a direct prognostic factor for NSCLC patients. More detailed prospective studies are needed to identify direct prognostic factors in these patients.

Introduction: Head and neck squamous cell carcinomas (HNSCCs) are cancers with generally poor prognosis. Outcomes have not improved in decades, with more than half of the patients presenting with lymph node metastases at the time of diagnosis. A unique subtype of HNSCC, cancer of unknown primary of the head and neck (HNCUP) is associated with a poor outcome. Increased expression of the D2-40 gene (podoplanin) has been described for several human malignancies and has been associated with increased metastatic potential of cancer cells.

Methods: In order to examine the role of podoplanin in lymph node metastasis of HNSCC generally and HNCUP specifically, we evaluated the prognostic impact of podoplanin expression in HNSCC- (n = 68) and HNCUP-associated lymph node metastases (n = 30). The expression of podoplanin was analyzed by immunohistochemical staining of lymph node tissue samples and correlated with clinical and histopathological data.

Results: We found a non-significant tendency towards a higher podoplanin expression in HNCUP compared to HNSCC lymph node metastases and a significant correlation between a high podoplanin expression and advanced node-stage classification. Podoplanin expression had no significant impact on overall survival for both groups and did not correlate with human papillomavirus tumor status.

Conclusion: Taken together, our results suggest that upregulation of podoplanin may be associated with a stimulation of lymphatic metastasis in head and neck cancer.

Breast cancer is one of the most threatening malignant tumors in women worldwide; hence, investigators are continually performing novel research in this field. However, an accurate prediction of its prognosis and postoperative recovery remains difficult. The severity of breast cancer is patient-specific and affected by several health factors; thus, unknown mechanisms may affect its progression. This article analyzes existing literature on breast cancer, ranging from the discovery of ghrelin to its present use, and aims to provide a reference for future research into breast cancer mechanisms and treatment-plan improvement. Various parts of ghrelin have been associated with breast cancer by direct or indirect evidence. The ghrelin system may encompass the direction of expanding breast cancer treatment methods and prognostic indicators. Therefore, we compiled almost all studies on the relationship between the ghrelin system and breast cancer, including unacylated ghrelin, its GHRL gene, ghrelin O-acyltransferase, the receptor growth hormone secretagogue receptor, and several splice variants of ghrelin to lay the foundation for future research.

Background: Fidgetin-like 1 (FIGNL1) participates in tumor resistance by playing the function of homologous recombination repair(HRR). However, the role of FIGNL1 in non-small cell lung cancer (NSCLC) is still unclear. This study aims to understand the expression of FIGNL1 in NSCLC and preliminarily explore its relationship with cisplatin resistance.

Methods: FIGNL1 messenger RNA (mRNA) was analyzed in 1018 NSCLC tissues and 111 adjacent tissues using The Cancer Genome Atlas program. FIGNL1mRNA in cisplatin-resistant and cisplatin-sensitive cell lines was analyzed by the Gene Expression Omnibus project. FIGNL1 protein was detected in 58 NSCLC tissues and 58 adjacent tissues by immunohistochemistry. The relationship between FIGNL1, clinical pathological characteristics and disease-free survival was retrospectively analyzed. Gene ontology was used to analyze the biological process mainly involving FIGNL1, and STRING online constructed its protein interaction network and screened the key genes (hub genes).

Results: The Cancer Genome Atlas showed that FIGNL1mRNA was higher in 1018 NSCLC tissues than in 111 adjacent tissues (P < 0.05). In the dataset "GSE157692," FIGNL1mRNA was higher in cisplatin-resistant cell lines (P = 3.80e-05). The hub genes in FIGNL1 and HRR directions are RAD51 and CCDC36. Immunohistochemistry showed that the FIGNL1 protein in 58 NSCLC tissues was higher than that in 58 adjacent tissues (P < 0.01). FIGNL1 is associated with gender, histopathological type, and nerve invasion in NSCLC. The disease-free survival in NSCLC patients with high FIGNL1 expression was shorter (P = 0.032).

Conclusion: FIGNL1 is associated with poor prognosis in NSCLC, and cisplatin resistance may be involved. These observations provide a clinical basis for exploring FIGNL1 as a potential biomarker for cisplatin resistance in NSCLC.

Background: Peripheral neutrophil-lymphocyte ratio (NLR), reflecting immune-inflammation status, shows great potential for tumor progression and outcome. Pre-treatment NLR does not fully reflect the immune-inflammatory response to treatment. This study aimed to introduce the NLR trend as a new indicator and to investigate its prognostic value in patients with nasopharyngeal carcinoma receiving radiotherapy.

Methods: This retrospective study evaluated patients with nasopharyngeal carcinoma treated with radiotherapy. The NLR trend value was calculated from the fitted line gradient via the NLRs before, during (at least once), and after each patient's first radiotherapy. The Kaplan-Meier curve and log-rank test were used to calculate and compare survival outcomes of different pretreatment NLRs and NLR trends for progression-free survival, locoregional recurrence-free survival (LRFS), and overall survival at 3 and 5 years. Multivariate Cox regression analyses were performed to assess the association between the NLR trend plus 3- and 5-year overall survival.

Results: The study included 528 patients. A lower NLR trend predicted worse progression-free survival, LRFS, plus 3- and 5-year overall survival. Multivariate Cox regression analysis showed that the NLR trend independently predicted 3- and 5-year overall survival. Sub-group analysis showed that the prognosis of patients with a low pretreatment NLR and a high NLR trend were superior to those of other groups.

Conclusion: The NLR trend independently predicted the prognosis of patients with nasopharyngeal carcinoma receiving radiotherapy. The NLR trend and the pretreatment NLR combination is more precise than pretreatment NLR in predicting prognosis. A high NLR trend may be evidence of a positive immune response to radiotherapy in patients with nasopharyngeal carcinoma.

Background: A whole-exome or targeted cancer genes panel by next-generation sequencing has been used widely in assisting individualized treatment decisions. Currently, multiple algorithms are developed to estimate DNA copy numbers based on sequencing data, which makes a comprehensive global glance at chromosomal integrity possible. We aim to classify gastric cancers based on chromosomal integrity to guide personalized therapy.

Methods: We investigated copy number variations (CNV) across the entire genome of 124 gastric carcinomas via exome or targeted sequencing. Chromosomal integrity was classified as chromosomal stability (CS), chromosomal instability (CIN) and intermediate state (CIN/CS) based on CNV results. Chromosomal integrity was correlated to molecular features and clinical characteristics.

Results: According the states of chromosomal integrity, gastric carcinomas can be stratified into two cohorts: CS and CIN. Our results showed a significant relationship between CIN status and TP53 mutation, but not RB1, phosphatase and tensin homolog (PTEN), or other reported DNA damage repair genes. The mutation frequency of the TP53 gene had great relevance. Our study initially revealed clinical significance of chromosomal integrity that CIN patients were prone to HER2-positive and mucinous adenocarcinoma, while CS patients were a diffuse subtype and poorly differentiated but had longer overall survival.

Conclusions: We classified gastric carcinomas into two states of chromosomal integrity with clinical implications. The dichotomy is applicable to clinical transformation. We proposed that classifying gastric cancers based on chromosomal integrity would enable us to achieve personalized therapy for patients and may be beneficial to patient stratification in future clinical trials.