Cancer-testis gene PIWIL1 promotes cell proliferation, migration, and invasion in lung adenocarcinoma

Abstract

Piwi-like RNA-mediated gene silencing 1 (PIWIL1) has been identified as a novel extremely highly expressed cancer-testis (CT) gene in lung adenocarcinoma. However, the exact function and mechanism of PIWIL1 in lung adenocarcinoma remains unclear. Herein, we sought to investigate the role of PIWIL1 in the occurrence and development of lung adenocarcinoma. We examined the expression pattern of PIWIL1 in The Cancer Genome Atlas (TCGA) lung adenocarcinoma samples, and validated it by Real-Time PCR (RT-PCR) in additional 21 paired lung adenocarcinoma tissues and 16 normal tissues. Subsequently, we explored the biological function of PIWIL1 in A549 and H1299 cell lines by gain and loss-of-function analyses. Using TCGA lung adenocarcinoma data, we further performed coexpression and Gene Ontology (GO) analyses, and analyzed the association of DNA methylation levels in PIWIL1 promoter region with its expression. Finally, we evaluated its expression in different mutation status of significantly mutated genes (SMGs) in TCGA lung adenocarcinoma data. We observed that PIWIL1 was expressed in testis and lung adenocarcinoma but not in other normal tissues, and its high expression was associated with shortened survival of lung cancer patients. Overexpression of PIWIL1 could facilitate the proliferation, invasion and migration of lung adenocarcinoma cells and vice versa. GO analysis revealed that PIWIL1 upregulated genes were enriched in embryonic development, cell proliferation and regulation of transcription. Moreover, promoter DNA hypomethylation of PIWIL1 could contribute to its aberrant expression in tumors. Interestingly, PIWIL1 expression was significantly higher in patients without hepatocyte growth factor (HGF) or serine/threonine kinase 11 (STK11) mutation (P = 0.006 and 0.005, respectively). PIWIL1 is an epidriver gene in lung adenocarcinoma, indicating a potential target for further therapy.

PIWIL1 is a novel extremely highly expressed cancer-testis gene in lung adenocarcinoma. PIWIL1 could promote the ability of proliferation, invasion, and migration in lung adenocarcinoma. The expression status of PIWIL1 is regulated by methylation in promoter region.

http://ift.tt/2hYzpXg

Prognostic value of PD-L1 expression in combination with CD8+ TILs density in patients with surgically resected non-small cell lung cancer

Abstract

To investigate the prognostic value of PD-L1 expression combined with CD8⁺ TILs density in patients with resected NSCLC and correlations with clinicopathological features. We retrospectively enrolled 178 patients with resected NSCLC from 2011 to 2015. All surgical primary and 58 matched metastatic lymph node specimens were tested for PD-L1, CD8⁺ TILs, and oncogenic alterations. PD-L1⁺ was detected in 71 (39.9%) and CD8^high TILs in 74 (41.6%) cases. Smoking, SqCC, and EGFR⁻ were associated with both PD-L1⁺ and CD8^high TILs. Patients with CD8^high TILs had longer OS (P = 0.012). PD-L1⁻ was significantly associated with longer OS in patients with oncogenic alterations (P = 0.047). By multivariate analysis, CD8^high TILs (HR = 0.411; 95% CI, 0.177–0.954; P = 0.038), rather than PD-L1, was the independent predictive factor for OS. The longest and shortest OS were achieved in patients with PD-L1⁺/CD8^high and PD-L1⁺/CD8^low, respectively (P = 0.025). Inconsistent PD-L1 expression levels were observed in 23 of 58 (39.7%) patients with primary and matched metastatic lymph node specimens. Of them, CD8^high TILs was significantly associated with longer OS in patients with metastatic lymph nodes and/or consistent PD-L1 expression (P = 0.017 and 0.049, respectively). The combination of PD-L1 and CD8⁺ TILs density, instead of PD-L1 alone, suggested impressive prognostic values in NSCLC patients. Less than half of patients with resected NSCLC experienced inconsistent PD-L1 expression between primary and metastatic lesions. The level of PD-L1 expression in advanced NSCLC needs to be evaluated more comprehensively.

Combination of PD-L1 and CD8⁺ TILs density may suggest impressive prognostic value in NSCLC patients instead of PD-L1 alone. Less than half of patients with resected NSCLC experienced inconsistent PD-L1 expression between primary and metastatic lesions, and significance of PD-L1 expression in a single-biopsy specimen in advanced NSCLC may be overestimated in clinical practice.

http://ift.tt/2jRngUs

Patient satisfaction with information on oral anticancer agent use

Abstract

Adequate information on oral anticancer agent (OACA) use is an essential element of optimal cancer care. The present study aimed to get insight into the experiences of patients with information on OACA treatment and their characteristics regarding information dissatisfaction. Patients of four Dutch university hospitals using OACA participated in this observational study and completed the Satisfaction with Information about Medicines Scale (SIMS), EORTC Quality of Life Questionnaire-C30, Brief Illness Perception Questionnaire, and Beliefs about Medicines Questionnaire-Specific. Logistic regression analyses were used to determine factors associated with dissatisfaction with information. Patients (n = 208) using capecitabine (35%), lenalidomide (15%), imatinib (14%), temozolomide (12%), sunitinib (11%), thalidomide (5%), dasatinib (4%), erlotinib (2%), and nilotinib (2%) participated. Information on the following SIMS-items was inadequate: how OACA elicit their effect, how long it takes before treatment works, how to conclude that treatment is effective, the risk of side effects and its management, interference with sex life, drowsiness, interference with other medication and alcohol and what to do in case of a missed dose. Younger age, hematological malignancy, dyspnoea, positive perception of consequences of the cancer, low perception of treatment control, and indifferent attitude towards OACA were associated with dissatisfaction with information. In conclusion, a considerable number of patients would have appreciated receiving more information on specific issues relating to the consequences of OACA treatment such as the effects and side effects of OACA and the interference of treatment with various aspects of their daily life. Oncologists, hematologists, lung-oncologists and pharmacists may reconsider the provision of information on OACA treatment.

This observational study showed that a substantial number of cancer patients perceived a lack of information on oral anticancer agent (OACA) treatment. Particularly information on the following subjects should be improved: self-monitoring of treatment effectiveness, side effects and their management, interference of treatment with sex life, interference of treatment with other medicines and alcohol use, and what to do in case of missed doses. Healthcare providers may reconsider the provision of information on OACA treatment.

http://ift.tt/2hYzcDs

Cancer-testis gene PIWIL1 promotes cell proliferation, migration, and invasion in lung adenocarcinoma

Abstract

Piwi-like RNA-mediated gene silencing 1 (PIWIL1) has been identified as a novel extremely highly expressed cancer-testis (CT) gene in lung adenocarcinoma. However, the exact function and mechanism of PIWIL1 in lung adenocarcinoma remains unclear. Herein, we sought to investigate the role of PIWIL1 in the occurrence and development of lung adenocarcinoma. We examined the expression pattern of PIWIL1 in The Cancer Genome Atlas (TCGA) lung adenocarcinoma samples, and validated it by Real-Time PCR (RT-PCR) in additional 21 paired lung adenocarcinoma tissues and 16 normal tissues. Subsequently, we explored the biological function of PIWIL1 in A549 and H1299 cell lines by gain and loss-of-function analyses. Using TCGA lung adenocarcinoma data, we further performed coexpression and Gene Ontology (GO) analyses, and analyzed the association of DNA methylation levels in PIWIL1 promoter region with its expression. Finally, we evaluated its expression in different mutation status of significantly mutated genes (SMGs) in TCGA lung adenocarcinoma data. We observed that PIWIL1 was expressed in testis and lung adenocarcinoma but not in other normal tissues, and its high expression was associated with shortened survival of lung cancer patients. Overexpression of PIWIL1 could facilitate the proliferation, invasion and migration of lung adenocarcinoma cells and vice versa. GO analysis revealed that PIWIL1 upregulated genes were enriched in embryonic development, cell proliferation and regulation of transcription. Moreover, promoter DNA hypomethylation of PIWIL1 could contribute to its aberrant expression in tumors. Interestingly, PIWIL1 expression was significantly higher in patients without hepatocyte growth factor (HGF) or serine/threonine kinase 11 (STK11) mutation (P = 0.006 and 0.005, respectively). PIWIL1 is an epidriver gene in lung adenocarcinoma, indicating a potential target for further therapy.

PIWIL1 is a novel extremely highly expressed cancer-testis gene in lung adenocarcinoma. PIWIL1 could promote the ability of proliferation, invasion, and migration in lung adenocarcinoma. The expression status of PIWIL1 is regulated by methylation in promoter region.

from Cancer via ola Kala on Inoreader http://ift.tt/2hYzpXg
via IFTTT

Prognostic value of PD-L1 expression in combination with CD8+ TILs density in patients with surgically resected non-small cell lung cancer

Abstract

To investigate the prognostic value of PD-L1 expression combined with CD8⁺ TILs density in patients with resected NSCLC and correlations with clinicopathological features. We retrospectively enrolled 178 patients with resected NSCLC from 2011 to 2015. All surgical primary and 58 matched metastatic lymph node specimens were tested for PD-L1, CD8⁺ TILs, and oncogenic alterations. PD-L1⁺ was detected in 71 (39.9%) and CD8^high TILs in 74 (41.6%) cases. Smoking, SqCC, and EGFR⁻ were associated with both PD-L1⁺ and CD8^high TILs. Patients with CD8^high TILs had longer OS (P = 0.012). PD-L1⁻ was significantly associated with longer OS in patients with oncogenic alterations (P = 0.047). By multivariate analysis, CD8^high TILs (HR = 0.411; 95% CI, 0.177–0.954; P = 0.038), rather than PD-L1, was the independent predictive factor for OS. The longest and shortest OS were achieved in patients with PD-L1⁺/CD8^high and PD-L1⁺/CD8^low, respectively (P = 0.025). Inconsistent PD-L1 expression levels were observed in 23 of 58 (39.7%) patients with primary and matched metastatic lymph node specimens. Of them, CD8^high TILs was significantly associated with longer OS in patients with metastatic lymph nodes and/or consistent PD-L1 expression (P = 0.017 and 0.049, respectively). The combination of PD-L1 and CD8⁺ TILs density, instead of PD-L1 alone, suggested impressive prognostic values in NSCLC patients. Less than half of patients with resected NSCLC experienced inconsistent PD-L1 expression between primary and metastatic lesions. The level of PD-L1 expression in advanced NSCLC needs to be evaluated more comprehensively.

Combination of PD-L1 and CD8⁺ TILs density may suggest impressive prognostic value in NSCLC patients instead of PD-L1 alone. Less than half of patients with resected NSCLC experienced inconsistent PD-L1 expression between primary and metastatic lesions, and significance of PD-L1 expression in a single-biopsy specimen in advanced NSCLC may be overestimated in clinical practice.

from Cancer via ola Kala on Inoreader http://ift.tt/2jRngUs
via IFTTT

Patient satisfaction with information on oral anticancer agent use

Abstract

Adequate information on oral anticancer agent (OACA) use is an essential element of optimal cancer care. The present study aimed to get insight into the experiences of patients with information on OACA treatment and their characteristics regarding information dissatisfaction. Patients of four Dutch university hospitals using OACA participated in this observational study and completed the Satisfaction with Information about Medicines Scale (SIMS), EORTC Quality of Life Questionnaire-C30, Brief Illness Perception Questionnaire, and Beliefs about Medicines Questionnaire-Specific. Logistic regression analyses were used to determine factors associated with dissatisfaction with information. Patients (n = 208) using capecitabine (35%), lenalidomide (15%), imatinib (14%), temozolomide (12%), sunitinib (11%), thalidomide (5%), dasatinib (4%), erlotinib (2%), and nilotinib (2%) participated. Information on the following SIMS-items was inadequate: how OACA elicit their effect, how long it takes before treatment works, how to conclude that treatment is effective, the risk of side effects and its management, interference with sex life, drowsiness, interference with other medication and alcohol and what to do in case of a missed dose. Younger age, hematological malignancy, dyspnoea, positive perception of consequences of the cancer, low perception of treatment control, and indifferent attitude towards OACA were associated with dissatisfaction with information. In conclusion, a considerable number of patients would have appreciated receiving more information on specific issues relating to the consequences of OACA treatment such as the effects and side effects of OACA and the interference of treatment with various aspects of their daily life. Oncologists, hematologists, lung-oncologists and pharmacists may reconsider the provision of information on OACA treatment.

This observational study showed that a substantial number of cancer patients perceived a lack of information on oral anticancer agent (OACA) treatment. Particularly information on the following subjects should be improved: self-monitoring of treatment effectiveness, side effects and their management, interference of treatment with sex life, interference of treatment with other medicines and alcohol use, and what to do in case of missed doses. Healthcare providers may reconsider the provision of information on OACA treatment.

from Cancer via ola Kala on Inoreader http://ift.tt/2hYzcDs
via IFTTT

Genomic risk prediction of aromatase inhibitor-related arthralgia in patients with breast cancer using a novel machine-learning algorithm

Abstract

Many breast cancer (BC) patients treated with aromatase inhibitors (AIs) develop aromatase inhibitor-related arthralgia (AIA). Candidate gene studies to identify AIA risk are limited in scope. We evaluated the potential of a novel analytic algorithm (NAA) to predict AIA using germline single nucleotide polymorphisms (SNP) data obtained before treatment initiation. Systematic chart review of 700 AI-treated patients with stage I-III BC identified asymptomatic patients (n = 39) and those with clinically significant AIA resulting in AI termination or therapy switch (n = 123). Germline DNA was obtained and SNP genotyping performed using the Affymetrix UK BioBank Axiom Array to yield 695,277 SNPs. SNP clusters that most closely defined AIA risk were discovered using an NAA that sequentially combined statistical filtering and a machine-learning algorithm. NCBI PhenGenI and Ensemble databases defined gene attribution of the most discriminating SNPs. Phenotype, pathway, and ontologic analyses assessed functional and mechanistic validity. Demographics were similar in cases and controls. A cluster of 70 SNPs, correlating to 57 genes, was identified. This SNP group predicted AIA occurrence with a maximum accuracy of 75.93%. Strong associations with arthralgia, breast cancer, and estrogen phenotypes were seen in 19/57 genes (33%) and were functionally consistent. Using a NAA, we identified a 70 SNP cluster that predicted AIA risk with fair accuracy. Phenotype, functional, and pathway analysis of attributed genes was consistent with clinical phenotypes. This study is the first to link a specific SNP/gene cluster to AIA risk independent of candidate gene bias.

Aromatase inhibitor-related arthralgias (AIA) are common and may lead to therapy noncompliance. Whereas traditional gene studies to identify arthralgia risk have been limited in scope, we employed a novel analytic algorithm to link a specific SNP/gene cluster to AIA risk independent of candidate gene bias.

http://ift.tt/2A57Wb3