Correlation of tumor‐infiltrating immune cells of melanoma with overall survival by immunogenomic analysis

xloma.fota13 shared this article with you from Inoreader Correlation of tumor‐infiltrating immune cells of melanoma with overall survival by immunogenomic analysis Via Cancer Medicine Immunotherapy has shown excellent responses in melanoma, while the reaction is low. However, the molecular mechanisms of tumor infiltrated immune cells have not been explored. In this study, we found that higher ESTIMATE and immune scores were associated with a clinical‐stage in melanoma patients and also filtered the crosstalks between cells that immune cells. Our work revealed the immune cellular and molecular characteristics of melanoma, providing a method for selecting targets promoting immunotherapy efficacy. Abstract Aims Different types of tumor‐infiltrating immune cells not only augment but also dampen antitumor immunity in the microenvironment of melanoma. Therefore, it is critical to provide an overview of tumor‐infiltrating immune cells in melanoma and explore a novel strategy for immunotherapies. Methods We analyzed the immune states of different stages in melanoma patients by the immune, stromal, and estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE) scores. Immune cell types were identified by the estimating relative subsets of RNA transcripts (CIBERSORTx) algorithm in 471 melanoma and 324 healthy tissues. Moreover, we performed a gene set variation analysis (GSVA) to determine the differentially regulated pathways in the tumor microenvironment. Results In melanoma cohorts, we found that ESTIMATE and immune scores were involved in survival or tumor clinical stage. Among the 22 immune cells, CD8+ T cells, M2 macrophages, and regulatory T cells (Tregs) showed significant differences using the CIBERSORTx algorithm. Furthermore, GSVA identified the immune cell‐related pathways; the primary immunodeficiency pathway, intestinal immune network for IgA, and TGF‐β pathways were identified as participants of the crosstalk in CD8+ T cells, Tregs, and M2 macrophages in the melanoma microenvironment. Conclusion These results reveal the cellular and molecular characteristics of immune cells in melanoma, providing a method for selecting targets of immunotherapies and promoting the efficacy of therapies for the treatment of melanoma. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The immune phenotype of tongue squamous cell carcinoma predicts early relapse and poor prognosis

xloma.fota13 shared this article with you from Inoreader The immune phenotype of tongue squamous cell carcinoma predicts early relapse and poor prognosis Via Cancer Medicine In patients with squamous cell carcinoma of the oral tongue (OTSCC), current tumor node metastasis staging system fails to identify at‐risk patients associated with early relapse and poor prognosis despite complete surgical resection. Given the importance of tumor‐infiltrating lymphocytes in the development of cancers, here we investigated the prognostic significance of the immune phenotype in OTSCC. Abstract Background In patients with squamous cell carcinoma of the oral tongue (OTSCC), current tumor node metastasis staging system fails to identify at‐risk patients associated with early relapse and poor prognosis despite complete surgical resection. Given the importance of tumor‐infiltrating lymphocytes (TILs) in the development of cancers, here we investigated the prognostic significance of the immune phenotype in OTSCC. Methods Hematoxylin‐eosin stained sections of OTSCCs from 211 patients were evaluated. Cancers were classified as (a) immune‐inflamed when TILs were found next to tumor cell nests; (b) immune‐excluded when TILs were found in the stroma, outside the tumor; and (c) immune‐desert for tumors lacking lymphocyte infiltrate. The prognostic significance of these immune phenotypes classes was investigated. Data were further validated on an independent cohort from The Cancer Genome Atlas database. Results Immune‐desert phenotype was the least represented group of OTSCCs in our cohort (11.8%) and served as an independent prognostic factor. Patients with immune‐desert tumors exhibited worse disease‐specific survival (HR = 2.673; [CI: 95% 1.497‐4.773]; P = .001), overall survival (HR = 2.591; [CI: 95% 1.468‐4.572]; P = .001), and disease‐free survival (HR = 2.313; [CI: 95% 1.118‐4.786]; P = .024) at multivariate analysis. Conclusions We identified a specific subgroup of OTSCCs with poor prognosis. Tumor‐infiltrating lymphocytes density and localization could serve as an integrative parameter to the current staging system and inform the selection of most appropriate treatments. In particular, the tumor immune phenotype could improve the stratification of patients with more aggressive disease. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Associations between genetic variants of KIF5B, FMN1, and MGAT3 in the cadherin pathway and pancreatic cancer risk

xloma.fota13 shared this article with you from Inoreader Associations between genetic variants of KIF5B, FMN1, and MGAT3 in the cadherin pathway and pancreatic cancer risk Via Cancer Medicine We assessed associations between genetic variants in 109 cadherin‐related genes and pancreatic cancer risk by using genotyping data from two available genome‐wide association study datasets for 8477 cases and 6946 controls of European ancestry. We identified three novel PanC risk‐associated SNPs, KIF5B rs211304 C > G, FMN1 rs117648907 C > T and MGAT3 rs34943118 T > C. We also demonstrated potential functions of these risk loci, especially for the SNP rs211304 and rs34943118, to be associated with mRNA expression levels of KIF5B and MGAT3, respectively. Abstract Because the cadherin‐mediated signaling pathway promotes cancer progression, we assessed associations between genetic variants in 109 cadherin‐related genes and risk of pancreatic cancer (PanC) by using genotyping data from publically available genome‐wide association studies (GWAS) datasets comprising 15,423 individuals of European ancestry. After initial single‐locus analyses and subsequent meta‐analysis with multiple testing correction for 29,963 single‐nucleotide polymorphisms (SNPs), 11 SNPs remained statistically significant (p < 0.05). In the stepwise logistic regression analysis, three independent PanC risk‐associated SNPs (KIF5B rs211304 C > G, FMN1 rs117648907 C > T, and MGAT3 rs34943118 T > C) remained statistically significant (p < 0.05), with odds ratios of 0.89 (95% confidence interval = 0.82–0.95 and p = 6.93 ×&nbs p;10−4), 1.33 (1.13–1.56 and 2.11 × 10−4), and 1.11 (1.05–1.17 and 8.10 × 10−5), respectively. Combined analysis of unfavorable genotypes of these three independent SNPs showed an upward trend in the genotype‐risk association (p trend < 0.001). Expression quantitative trait loci analyses indicated that the rs211304 G and rs34943118 C alleles were associated with increased mRNA expression levels of KIF5B and MGAT3, respectively (all p < 0.05). Additional bioinformatics prediction suggested that these three SNPs may affect enhancer histone marks that likely have an epigenetic effect on the genes. Our findings provide biological clues for these PanC risk‐associated SNPs in cadherin‐related genes in European ancestry populations, possibly by regulating the expression of the affected genes. However, our findings need to be validated in additional population, molecular and mechanistic investigations. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The prognostic role of C‐reactive protein in patients with head and neck squamous cell carcinoma: A meta‐analysis

xloma.fota13 shared this article with you from Inoreader The prognostic role of C‐reactive protein in patients with head and neck squamous cell carcinoma: A meta‐analysis Via Cancer Medicine Our meta‐analysis demonstrated that an elevated pretreatment of CRP indicates poor prognosis in HNSCC. Therefore, CRP is an indicator of the prognosis of patients with HNSCC and can be recommended for assessing prognoses in clinical work. Abstract Background The prognostic role of the C‐reactive protein (CRP) in head and neck squamous cell carcinoma (HNSCC) has not been well investigated. This meta‐analysis aimed to evaluate the prognostic relevance of elevated CRP levels in patients with HNSCC. Methods A relevant literature search was performed in PubMed, Web of Science, and Embase up to September 1, 2020. The pooled odds ratio and hazard ratio (HR) with 95% confidence interval (CI) were applied to evaluate the difference in overall survival (OS), progress‐free survival (PFS), and cancer‐specific survival (CSS) between patients with high CRP and those without. The pooled odds ratio (OR) with 95% CI were used to assess the association between CRP and clinicopathological features. Results A total of 17 studies, including 4449 patients, were included. Pooled results showed that an elevated CRP was associated with worse OS (HR = 1.48, 95% CI: 1.24‐1.77), CSS (HR = 1.85, 95% CI: 1.38‐2.46), and PFS (HR = 1.73, 95% CI: 1.38‐2.17). Male patients, lymph node metastases, and higher tumor stage were related to elevated CRP level (OR = 1.67, 95% CI: 1.34‐2.09; OR = 2.40, 95% CI: 1.44‐3.99; OR = 1.39, 95% CI: 1.12‐1.74). Conclusion Our meta‐analysis demonstrated that an elevated pretreatment of CRP indicates poor prognosis in HNSCC. Therefore, CRP is an indicator of the prognosis of patients with HNSCC and can be recommended for assessing prognoses in clinical work. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

MiR‐362 suppresses cervical cancer progression via directly targeting BAP31 and activating TGFβ/Smad pathway

xloma.fota13 shared this article with you from Inoreader MiR‐362 suppresses cervical cancer progression via directly targeting BAP31 and activating TGFβ/Smad pathway Via Cancer Medicine Through in vivo and in vitro experiments, our findings demonstrated that miR‐362 works as an anti‐oncomiR that inhibits proliferation and promotes apoptosis in cervical cancer cells via BAP31 and TGFβ/Smad pathway. Overexpression of miR‐362 might be a potential therapeutic strategy for cervical cancer. Abstract BAP31 (B‐cell receptor‐associated protein 31) is an important regulator of intracellular signal transduction and highly expressed in several cancer tissues or testicular tissues. Our previous study had revealed that elevated BAP31 plays a crucial role in the progress and metastasis of cervical cancer. Even so, the precise mechanism of abnormal BAP31 elevation in cervical cancer has not been fully elucidated. We revealed that the expression of BAP31 was mainly regulated by microRNA‐362 (miR‐362), which was markedly downregulated in cervical cancer tissues and negatively correlated with clinical tumor staging. Overexpression of miR‐362 inhibited cervical cancer cell proliferation and increased the proportion of apoptotic cells. Furthermore, miR‐362 reduced the tumor sizes and prolonged mice survival time in xenograft nude mice model. Finally, we demonstrated that the BAP31/SPTBN1 complex regulated tumor progression through the Smad 2/3 pathway under the control of miR‐ 362. Collectively, our findings demonstrated that miR‐362 could work as an anti‐oncomiR that inhibits proliferation and promotes apoptosis in cervical cancer cells via BAP31 and TGFβ/Smad pathway. Overexpression of miR‐362 might be a potential therapeutic strategy for cervical cancer. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clinical characteristics and management of immune checkpoint inhibitor‐related pneumonitis: A single‐institution retrospective study

xloma.fota13 shared this article with you from Inoreader Clinical characteristics and management of immune checkpoint inhibitor‐related pneumonitis: A single‐institution retrospective study Via Cancer Medicine This study revealed for the first time the clinical characteristics, diagnosis, and treatment of CIPs in Chinese cancer patients. The recommended starting dose of 1–2 mg/kg GCS is feasible, but the duration of GCS ≥30 mg/day should be controlled, as acquired infections during the GCS treatment rather than refractory CIP could be the main cause of CIP‐related deaths. Abstract Introduction The increasing application of immune checkpoint inhibitors (ICIs) will cause more checkpoint inhibitor‐related pneumonitis (CIP), which is a common cause of ICI‐related death. The clinical management of CIP needs further optimization. Methods Patients who were managed at Peking Union Medical College Hospital (PUMCH) between February 2017 and December 2019 with a diagnosis of CIP were retrospectively analyzed. Clinical data including clinical manifestations, radiologic data, laboratory and bronchoscopy results, treatments, and outcomes were collected and analyzed. The Mann–Whitney test was used to compare patients with and without co‐infections. Results In total, 48 CIP cases in 42 patients were analyzed. The median time from the first dose of ICI to the onset of CIP was 1.9 months (range: 0.1–13.7). Grade 3–4 (G3–4) accounted for 30 cases (71.4%). The most common symptoms were cough (88.1%) and dyspnea (78.6%). The median starting dose of equivalent prednisone (EP) was 55 mg (range: 30–200) for all patients. The median total duration of glucocorticosteroids (GCS) treatment was 42.5 days (range: 15−89). Three patients (7.14%) died because of infection. A higher starting dose and longer duration of GCS (≥30 mg/day; p = 0.001) were associated with opportunistic infection. Chest computed tomography (CT) showed diverse and asymmetrical lesions. Twelve patients were re‐challenged, and six patients developed recurrent CIP. Conclusions The clinical and imaging manifestations of CIP are various, and differential diagnosis of exclusion is essential. GCS at 1–2 mg/kg is feasible to treat CIP, but the duration of GCS ≥30 mg/day should be used with caution, given the high risk of acquired infections. Re‐challenges of ICI are feasible, but the recurrence of CIP needs to be closely monitored. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Disagreement between patient‐ and physician‐reported outcomes on symptomatic adverse events as poor prognosis in patients treated with first‐line cetuximab plus chemotherapy for unresectable metastatic colorectal cancer: Results of Phase II QUACK trial

xloma.fota13 shared this article with you from Inoreader Disagreement between patient‐ and physician‐reported outcomes on symptomatic adverse events as poor prognosis in patients treated with first‐line cetuximab plus chemotherapy for unresectable metastatic colorectal cancer: Results of Phase II QUACK trial Via Cancer Medicine The routine use of PROs could be complementary to physician‐reported outcomes to ensure the accurate assessment of symptomatic AEs and facilitate patient‐centered healthcare in clinical practice. Abstract The status and prognostic value of the disagreement between physician and patient assessments of symptomatic adverse events (AEs) remain unclear for patients with metastatic colorectal cancer treated with first‐line cetuximab plus chemotherapy. Paired data on patient‐reported outcomes using the EORTC QLQ‐C30 and physician‐reported outcomes using the NCI‐CTCAE for eight symptomatic AEs (fatigue, pain, insomnia, dyspnea, constipation, appetite loss, nausea/vomiting, and diarrhea) were collected from a prospective trial assessing the relationships between treatment efficacy, AEs, and quality of life. The overall agreement rates between patient and physician reporting at 4 weeks ranged from 40.2% to 76.5% for 129 patients. The level of agreement based on Cohen's κ statistics was slight to poor for dyspnea, pain, fatigue, and insomnia, while it was moderate to fair for the remaining AEs. No clinicopathological characteristics of disagreement were found. The underreporti ng by physicians ranged from 12.5% (nausea/vomiting) to 56.7% (fatigue). The 2‐year overall survival (OS) rate was more favorable for patients with high agreement than for those with low agreement (71.2% vs. 46.5%, p = .016), and the agreement status was an independent factor of OS (HR, 2.31; 95% CI, 1.13–4.71; p = .022). For patients who were reported as asymptomatic by the physician, the presence of patient‐reported symptoms resulted in a trend toward poor prognostic outcomes for appetite loss, dyspnea, diarrhea, and constipation. These findings provide the clinical importance of the monitoring of patient‐reported symptoms that can be complementary to physician‐reported data to ensure more accurate clinical outcomes. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.