scholarly journals Clinical Relevance of PD-L1 Expression and CD8+ T Cells’ Infiltration in Patients With Lung Invasive Mucinous Adenocarcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoling Xu ◽  
Na Li ◽  
Ding Wang ◽  
Wei Chen ◽  
Yun Fan
Keyword(s):  
Mucinous Adenocarcinoma ◽  
Target Therapy ◽  
Tumor Infiltrating Lymphocytes ◽  
Egfr Mutations ◽  
Chi Square ◽  
Genetic Characteristics ◽  
Kaplan Meier ◽  
Chi Square Test ◽  
Cox Proportional Hazard Regression ◽  
Invasive Mucinous Adenocarcinoma

BackgroundInvasive mucinous adenocarcinoma (IMA) of the lung is a rare and distinct subtype of adenocarcinoma. At present, people have no idea whether IMA patients can benefit from immunotherapy and target therapy; thus there is an urgent need to clarify the immune microenvironment and genetic characteristics of this cohort.MethodsA total of 31 IMA patients matched with 27 non-mucinous adenocarcinoma (non-IMA) patients were enrolled in this study, and clinical data was collected. The expression of PD-L1, CD8+ tumor-infiltrating lymphocytes (TILs) and ALK was determined by immunohistochemistry. Polymerase Chain Reaction was used to determine the mutations of EGFR. The Chi-square test, Kaplan–Meier method and Cox proportional hazard regression model were used to explore the correlations between these clinicopathological variables, survival and identify risk factors.ResultsOf the patients with IMA 9.7% (3/31) revealed positive PD-L1 expression and 35.5% (11/31) showed CD8+ TIL infiltration, which were markedly lower than that of non-IMA group [PD-L1: 48.1% (13/27); CD8: 81.5% (22/27)]. Moreover, five (16.1%) patients in IMA group and 10 (37.0%) patients in non-IMA group had EGFR mutations, and nine (29.0%) patients in IMA group and zero (0.0%) patient in non-IMA group had ALK rearrangements. Additionally, we observed that IMA patients with CD8+ TIL infiltration had a worse prognosis than CD8-negative group (P = 0.024). Multivariate analyses showed that CD8 was an independent prognostic factor for patient’s survival (HR = 5.60, 95% CI: 1.35–23.22, P = 0.017).ConclusionPatients with IMA have down-regulated expression of PD-L1 and less CD8+ TIL infiltration in tumor microenvironment. Besides, a lower frequency of EGFR mutations was detected in patients with IMA than non-IMA patients while a higher rate of ALK rearrangements was found. Our results provide important reference for therapy of lung IMA.

Genetic Alterations in Chinese Resected Lung Cancer with Invasive Mucinous Adenocarcinoma: Genomic Profiling and Prognostic Value Analysis

2021 ◽  
Author(s):  
James D. Klingensmith
Keyword(s):  
Mucinous Adenocarcinoma ◽  
Pi3k Pathway ◽  
Genetic Alterations ◽  
Egfr Mutations ◽  
Driver Mutations ◽  
Genetic Profile ◽  
Kras Mutations ◽  
Genetic Characteristics ◽  
Value Analysis ◽  
Invasive Mucinous Adenocarcinoma

Lung invasive mucinous adenocarcinoma (IMA) is a unique histological subtype with different clinical and pathological characteristics. Despite prior genomic investigations on lung IMA, little is known about the genetic features and prognosis-related biomarkers in Chinese surgically resected lung IMA. IMA showed a distinct genetic profile, with more diversified driver mutations and co-occurrence of tumor drivers/suppressors than non-IMA. From non-IMA to mixed-IMA to pure-IMA, the frequency of EGFR (72.0 percent vs. 40.0 percent vs. 23.1 percent, p=0.002) and ALK (undetected vs. 20.0 percent vs. 26.9%, p=0.015) changes exhibited a trend of steady decline and rise, respectively. KRAS mutations were more common in pure-IMA than in mixed-IMA, however the difference was statistically insignificant (23.1 percent vs. 4.0 percent, p=0.10). Pure-IMA had a lower rate of TP53 mutation than mixed-IMA and non-IMA (23.1 percent vs. 52.0 percent vs. 56.0 percent, p=0.03). Furthermore, IMA had fewer arm-level amplifications (p=0.04) and more arm-level deletions (p=0.004) than non-IMA, with a steady drop in amplification and rise in deletion frequency from non-IMA to mixed-IMA to pure-IMA, respectively. Patients with EGFR mutations (mDFS=30.3 vs. 16.0 months, HR=0.19, P=0.027) and PI3K pathway mutations (mDFS=36.0 vs. 16.0 months, HR=0.12, P=0.023) had longer DFS than patients with poorly differentiated tumors (mDFS=14.1 vs. 28.0 months, HR=3.75, p=0.037) or KRAS mutations (mDFS=13 KRAS mutations, PI3K pathway changes, and tumor differentiation status were all shown to be independent predictors with statistically significant effects on IMA patients' clinical outcomes in multivariate analysis. Our research shed light on the genomics of Chinese lung IMA that had been surgically removed. In IMA patients with stage III illness, we also discovered many genetic characteristics that might be used as indicators for postoperative recurrence.

scholarly journals Incidence and Predictors of Antiretroviral Treatment Modification in HIV-Infected Adults: A Brazilian Historical Cohort from 2001 to 2010

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Letícia Penna Braga ◽  
Cássia Cristina Pinto Mendicino ◽  
Edna Afonso Reis ◽  
Ricardo Andrade Carmo ◽  
Cristiane Menezes de Pádua
Keyword(s):  
Chi Square ◽  
Naive Patient ◽  
Historical Cohort ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Treatment Naïve ◽  
Chi Square Test ◽  
Belo Horizonte ◽  
Cox Proportional Hazard Regression

This study estimated the incidence of and time to first antiretroviral therapy (ART) modification. This longitudinal analysis comprised a sample of 236 patients from three HIV/AIDS referral centers in Belo Horizonte, Brazil—part of a major historical cohort. Inclusion criteria were as follows: having been treatment-naive patient ≥18 years old who initiated ART between 2001 and 2005 in these three referral centers. The main endpoint was time to first ART modification. Patients were followed up for five years, covering the period 2001–2010, during which time Pearson’s chi-square test was performed to compare ART modification between groups. Kaplan-Meier inverse survival curves were employed to describe the probability of ART modification and Cox proportional hazard regression was used to estimate the adjusted hazard ratio (aHR) of ART modification. Among 247 patients from the major cohort, 236 were eligible. Median follow-up time was 37.2 months and the contribution in person-months was 7,615.4 months. A total of 108 (45.8%) patients had their ART regimen modified at least once (incidence rate: 1.42 per 100 person-months). Adverse drug reactions were the main reason for ART modification. Women (aHR = 1.62; p=0.022) and patients on protease inhibitor- (PI-) based regimens (aHR = 2.70; p<0.001) were at higher risk of ART modification.

scholarly journals Ανοσοϊστοχημική μελέτη της έκφρασης της κινάσης ERK2 και των πρωτεϊνών των μεταγραφικών παραγόντων ETS-1 και φωσφορυλιωμένης STAT-1 σε διηθητικά καρκινώματα του μαστού

2014 ◽  
Author(s):  
Πέτρος Ραφαηλίδης
Keyword(s):  
Proportional Hazard ◽  
Chi Square ◽  
Mitogen Activated Protein Kinases ◽  
Extracellular Signal Regulated Kinase ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Chi Square Test ◽  
Cox Proportional Hazard Regression

ΕΙΣΑΓΩΓΗ. Η ΕRK2 κινάση (Extracellular signal-regulated kinase 2) ανήκει στο σύστημα των κινασών ΜAPK (Mitogen Activated Protein Kinases). Οι ΜAPK βρίσκονται ενδοκυττάρια στο κυτταρόπλασμα και ενεργοποιούνται μετά από διέγερση υποδοχέων (υποδοχέων τύπου τυροσινικής κινάσης, υποδοχέων που συνδέονται με G-πρωτεΐνη, ιντεγκρινών και διαύλων ασβεστίου) από εξωγενή ερεθίσματα. Μετά την ενεργοποίηση τους προκαλούν φωσφορυλίωση διαφόρων ουσιών, είτε στον πυρήνα είτε στο κυτταρόπλασμα, και ρυθμίζουν έτσι κυτταρικές δραστηριότητες όπως γονιδιακή έκφραση, μίτωση, κίνηση, μεταβολισμό και προγραμματισμένο κυτταρικό θάνατο και έχουν εμπλακεί στην παθογένεση του καρκίνου. Στους στόχους της κινάσης ΕRK2 μέσω της μεταγραφής των αντίστοιχων γονιδίων ανήκει η ETS-1 πρωτεΐνη και η φωσφορυλιωμένη πρωτεΐνη STAT-1 (pSTAT-1). Η ETS-1 πρωτεΐνη ανήκει στην οικογένεια των ΕΤS μεταγραφικών παραγόντων η οποία παίζει κύριο ρυθμιστικό ρόλο στην ανάπτυξη και ογκογένεση. Οι ETS πρωτεΐνες προσδένονται στους υποκινητές των γονιδίων στόχων τους και ενεργοποιούν την μεταγραφή τους. Η pSTAT-1 είναι το πρώτο μέλος της οικογένειας των STAT μεταγραφικών παραγόντων. Πρόσφατες μελέτες έχουν υποδείξει ότι επάγει την απόπτωση και αναστέλλει τον κυτταρικό πολλαπλασιασμό σε πειραματικά μοντέλα καρκίνου του μαστού. Η προγνωστική σημασία της ανοσοϊστοχημικής έκφρασης της ERK2 κινάσης και των ETS-1 και pSTAT-1 σε ασθενείς με καρκίνο του μαστού παραμένει αδιευκρίνιστη. Σκοπός της διδακτορικής αυτής διατριβής ήταν η διερεύνηση της έκφρασης της ERK2 κινάσης και της έκφρασης των πρωτεϊνών ETS-1 και pSTAT-1 σε ασθενείς με καρκίνο του μαστού. ΜΕΘΟΔΟΙ. Ανοσοϊστοχημική μέθοδος τριών βημάτων εφαρμόσθηκε σε τομές παραφίνης από 151 ασθενείς με διηθητικό καρκίνο μαστού με στόχο την εντόπιση της ERK2 κινάσης, της ETS-1 πρωτεΐνης και της pSTAT-1 και τη συσχέτιση τους με τις προγνωστικές κλινικοπαθολογοανατομικές παραμέτρους την επιβίωση των ασθενών. Δεν υπήρχε επαρκές υλικό για αξιολόγηση της έκφρασης της ETS-1 πρωτεΐνης σε 2 ασθενείς. Τα αποτελέσματα αξιολογήθηκαν με μονοπαραγοντική (Pearson’s-chi-square test) και πολυπαραγοντική στατιστική ανάλυση (μοντέλο λογιστικής παλινδρόμησης ή Cox proportional hazard regression model). Οι καμπύλες επιβίωσης προέκυψαν με δοκιμασία Kaplan-Meier και log rank στατιστική ανάλυση. ΑΠΟΤΕΛΕΣΜΑΤΑ. Η ERK2 ανιχνεύθηκε ανοσοϊστοχημικά στο κυτταρόπλασμα και τον πυρήνα των καρκινικών κυττάρων σε 37.7% και 19.2% των ασθενών αντιστοίχως. Η πυρηνική εντόπιση της ERK2 συσχετίσθηκε αντιστρόφως με τους ER (p=0.053) στην μονοπαραγοντική ανάλυση και στην πολυπαραγοντική ανάλυση (p=0.039), ενώ η κυτταροπλασματική ERK2 εκφραζόταν συχνότερα σε λοβιακά παρά πορογενή καρκινώματα (p=0.026) στην πολυπαραγοντική ανάλυση. Η πυρηνική έκφραση της ERK2 βρέθηκε να είναι ανεξάρτητος προγνωστικός παράγοντας μικρότερης ολικής επιβίωσης των ασθενών (p=0.04), ενώ η κυτταροπλασματική έκφραση της ERK2 είχε ανεξάρτητη ευνοϊκή επίδραση στην ελεύθερη νόσου επιβίωση και στην ολική επιβίωση (p<0.0001 και p=0.002, αντίστοιχα).Η ETS-1 πρωτεΐνη ανιχνεύθηκε σε 77.9% στο κυτταρόπλασμα και στο 46.3% στον πυρήνα των καρκινικών κυττάρων. Η κυτταροπλασματική έκφραση της ETS-1 συσχετιζόταν αντίστροφα με τον πυρηνικό και ιστολογικό βαθμό κακοηθείας (p= 0.004 και p=0.033, αντίστοιχα) στην μονοπαγοντική ανάλυση. Η έκφραση της ETS-1 πρωτεΐνης στο στρώμα παρουσίαζε αρνητική συσχέτιση με τους οιστρογονικούς υποδοχείς (p=0.003) στην μονοπαγοντική ανάλυση. Η μονοπαραγοντική ανάλυση έδειξε ότι η πυρηνική εντόπιση της ETS-1 σχετίζεται με μικρότερη ολική επιβίωση των μετα-εμμηνοπαυσιακών ασθενών (p =0.032).Η pSTAT-1 πρωτεΐνη ανιχνεύτηκε στο κυτταρόπλασμα και στον πυρήνα των καρκινικών κυττάρων σε ποσοστό 11,6% και 8,6%, αντίστοιχα. Στην ομάδα των προ-εμμηνοπαυσιακών ασθενών η κυτταροπλασματική pSTAT-1 συσχετίσθηκε παράλληλα με το στάδιο της νόσου (p=0.014) και την έκφραση των ER (p=0.008). Η κυτταροπλασματική pSTAT-1 είχε δυσμενή επίδραση στο διάστημα της ολικής επιβίωσης (p=0.048) στην ομάδα των προ-εμμηνοπαυσιακών ασθενών, ενώ προ-εμμηνοπαυσιακές ασθενείς με φαινότυπο ταυτόχρονης θετικής έκφρασης pSTAT-1/ ER ή PR παρουσίασαν μικρότερο διάστημα ελεύθερης νόσου επιβίωσης (p=0.012). Στην ομάδα των μετα-εμμηνοπαυσιακών ασθενών δεν παρατηρήθηκε καμία συσχέτιση με τις κλινικοπαθολογοαναντομικές παραμέτρους αλλά υπήρχε ευνοϊκή επίδραση στην ελεύθερη νόσου επιβίωση των ασθενών με το φαινότυπο ταυτόχρονης θετικής έκφρασης pSTAT-1/ ER ή PR (p=0.034). ΣΥΜΠΕΡΑΣΜΑΤΑ. Συπερασματικά η διατριβή αυτή συνολικά αναδεικνύει ότι το μονοπάτι της κινάσης ERK2 και των πρωτεϊνών ETS-1 και pSTAT-1 έχει έναν διακριτό ρόλο όσον αφορά την πρόγνωση σε γυναίκες με διηθητικό καρκίνο του μαστού. Συγκεκριμμένα, τα ευρήματα της διατριβής υποστηρίζουν τη σημασία της διαμερισματοποίησης της ERK2, όπως αυτή αποκαλύπτεται από την ανοσοϊστοχημική ανίχνευση της στο κυτταρόπλασμα και τον πυρήνα των καρκινικών κυττάρων του μαστού. Η πυρηνική εντόπιση της ERK2 σχετίζεται με μικρότερη ολική επιβίωση και η κυτταροπλασματική έκφραση της ERK2 με καλύτερη πρόγνωση των ασθενών. Η πυρηνική έκφραση της ETS-1 πρωτεΐνης σχετίζεται με μειωμένη ολική επιβίωση των μετα-εμμηνοπαυσιακών γυναικών. Όσον αφορά την έκφραση της pSTAT-1 η κυτταροπλασματική εντόπιση της σχετίσθηκε με μικρότερη ολική επιβίωση στις προ-εμμηνοπαυσιακές γυναίκες. Η πυρηνική έκφραση των πρωτεϊνών ERK2 και ETS-1 η δε κυτταροπλασματική της pSTAT-1 στα καρκινικά κύτταρα συσχετίσθηκε με δυσμενή πρόγνωση των ασθενών και ως εκ τούτου μπορούν να θεωρηθούν ως προγνωστικοί παράγοντες. Το γεγονός της έκφρασης της ERK2 και της ETS-1 στους πυρήνες των καρκινικών κυττάρων της δε pSTAT-1 στο κυτταρόπλασμα υποδηλώνουν σε συνδυασμό με το ανωτέρω εύρημα ότι η ενεργοποίηση γίνεται στους πυρήνες και το κυτταρόπλασμα αντίστοιχα. Αξίζει να αναφερθεί ότι τα ανωτέρω ευρήματα σχολιάζονται για πρώτη φορά στη διεθνή βιβλιογραφία. Περισσότερες μελέτες είναι απαραίτητες προς την πλήρη διαλεύκανση της σημασίας του μονοπατιού της ERK2 και των πρωτεϊνών ETS-1 και pSTAT-1 στον διηθητικό καρκίνο του μαστού και την αναζήτηση πιθανών θεραπευτικών παρεμβάσεων σε αυτό.

scholarly journals The role of phosphoprotein phosphatases catalytic subunit genes in pancreatic cancer

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Junjie Hang ◽  
Steven Yuk-Fai Lau ◽  
Ruohan Yin ◽  
Lina Zhu ◽  
Siyuan Zhou ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Prognostic Value ◽  
Chi Square ◽  
Catalytic Subunits ◽  
Beneficial Effects ◽  
Phosphoprotein Phosphatases ◽  
Kaplan Meier ◽  
Chi Square Test ◽  
Independent Cohort

Abstract Compelling evidence suggests that phosphoprotein phosphatases (PPPs) are involved in a large spectrum of physiological and pathological processes, but little is known about their roles in pancreatic cancer. We investigated the expression level, prognostic value, and potential function of PPPs with data from Oncomine, GEPIA, THPA, and TCGA databases and an independent cohort of patients with pancreatic cancer. Among all the PPP catalytic subunits (PPPcs), the transcription levels of PPP1CA, PPP1CB, PPP3CA, PPP3CB, and PPP4C were higher in pancreatic cancer than in normal pancreas (P&lt;0.01, fold change &gt; 2). Kaplan–Meier analysis showed that high transcription levels of PPP1CA, PPP1CB, PPP2CA, PPP2CB, PPP3CA, and PPP4C correlated with poorer survival. In contrast, patients with high levels of PPP3CB, PPP3CC, PPP5C, PPP6C, and PPEF2 had much better prognoses. Data from THPA and patients with pancreatic cancer enrolled in our hospital also confirmed the prognostic value of PPP1CA, PPP1CB, PPP2CA, PPP2CB, PPP3CA, PPP3CB, and PPP6C at the protein level. In addition, the Pearson Chi-square test showed that PPP3CB level was significantly correlated with T and N stages. GO and KEGG analyses showed that the genes and pathways related to the pathogenesis and progression of pancreatic cancer were greatly affected by alterations in PPPcs. Results of the present study suggest that PPP1CA, PPP1CB, PPP2CA, PPP2CB, and PPP3CA have deleterious effects but PPP3CB, PPP5C, and PPP6C have beneficial effects on pancreatic cancer.

scholarly journals Prognostic Significance of NBEAL2 in Liver hepatocellular carcinoma

2021 ◽  
Author(s):  
Yanghui Wen ◽  
Hui Su ◽  
Wuke Wang ◽  
Feng Ren ◽  
Haitao Jiang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
The Cancer Genome Atlas ◽  
Clinicopathological Parameters ◽  
Chi Square ◽  
Kaplan Meier ◽  
Chi Square Test ◽  
Liver Hepatocellular Carcinoma ◽  
The Relationship

Abstract Background: NBEAL2 is a member of the BEACH domain–containing protein (BDCP) family and little is known about the relationship between NBEAL2 and malignancy.Methods: We downloaded the Gene expression profiles and clinical data of Liver hepatocellular carcinoma(LIHC) form the Cancer Genome Atlas (TCGA) dataset. The expression difference of NBEAL2 in LIHC tissues and adjacent nontumor tissues was analyzed by R software. The relationship between NBEAL2 expression and clinicopathological parameters was evaluate by Chi-square test. The effect of NBEAL2 expression on survival were assessed by Kaplan–Meier survival analysis and Cox proportional hazards regression model. GSEA was used to explore the potential molecular mechanism of NBEAL2 in LIHC.Results: Up-regulation of NBEAL2 expression was detected in the LIHC tissue compared with adjacent nontumor tissues(P < 0.001). The chi-square test showed that no significant correlation between the expression level of NBEAL2 and various clinicopathological parameters (including T, N and M classifications) were detected. The Kaplan–Meier curves suggested that lower NBEAL2 expression was related with poor prognosis. The results of Multivariate analysis revealed that a lower expression of NBEAL2 in LIHC was an independent risk of poor overall survival (HR, 8.873; 95% CI, 1.159-67.936; P = 0.035). GSEA suggested that multiple tumor-related metabolic pathways were evidently enriched in samples with the low-NBEAL2 expression phenotype. Conlusion: NBEAL2 might act as an tumor suppressor gene in the progression of LIHC but the precise role of NBELA2 in LIHC needs further vertification.

CIP4 Expression is Associated With The Prognosis in Colorectal Cancer

2020 ◽  
Author(s):  
Keqian Zhang ◽  
Tianqi Mao ◽  
Zhicheng He ◽  
Xiaojiao Wu ◽  
Yu Peng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Lymphatic Invasion ◽  
Chi Square ◽  
Interacting Protein ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Chi Square Test ◽  
Student’S T

Abstract Background: This study was conducted to detect the expression of Cdc42 interacting protein 4 (CIP4) in patients with colorectal cancer (CRC), and explore the role of CIP4 in prognosis of CRC patients.Methods: The expression of CIP4 mRNA was determined by quantitative real-time PCR (qRT-CPR) and compared by student’s t-test between groups. Relationships of clinical characteristics and CIP4 expression were analyzed by Chi-square test. Kaplan-Meier curves were used to estimate the overall survival of CRC patients. And Cox regression analysis was conducted to identify the prognostic biomarkers for CRC patients.Results: The qRT-PCR results showed that CRC tissues were detected with significantly high CIP4 mRNA expression compared with adjacent normal controls (P<0.0001). The overexpression of CIP4 in CRC tissues was influenced by distant metastasis (P=0.021), lymphatic invasion (P=0.012) and TNM stage (P=0.006). But, other clinical factors including age, gender, differentiation and tumor site were proved to have no obvious effects on CIP4 expression (all, P>0.05). The survival curves showed that patients with high CIP4 expression generally lived shorter than those with low CIP4 expression (P<0.001). In addition, the multivariate analysis revealed that differentiation (P=0.044, HR=1.631, 95%CI=1.013-2.626) and CIP4 expression (P=0.000, HR=5.283, 95%CI=3.138-8.893) were of great prognostic significance for CRC patients.Conclusion: Taken together, up-regulation of CIP4 in CRC tissues represented poor prognosis for patients.

scholarly journals Microsurgical rhizotomy for trigeminal neuralgia in MS patients: technique, patient satisfaction, and clinical outcomes

2019 ◽  
Vol 130 (6) ◽  
pp. 1877-1888
Author(s):  
Mark G. Bigder ◽  
Sandeep Krishnan ◽  
E. Francis Cook ◽  
Anthony M. Kaufmann
Keyword(s):  
Trigeminal Neuralgia ◽  
Treatment Failure ◽  
Rank Test ◽  
Control Group ◽  
Chi Square ◽  
Time To Treatment ◽  
Pain Scores ◽  
Kaplan Meier ◽  
Time To Treatment Failure ◽  
Chi Square Test

OBJECTIVEPatients with multiple sclerosis (MS)–associated trigeminal neuralgia (TN) have higher recurrence and retreatment rates than non-MS patients. The optimal management strategy and role for microsurgical rhizotomy (MSR) for MS-TN remains to be determined. The aim of this study was to report time to treatment failure (TTF) and pain scores following MSR compared to percutaneous and Gamma Knife procedures.METHODSTime to treatment failure was analyzed after MSR (n = 14) versus prior procedures (n = 53) among MS-TN patients. Kaplan-Meier curves and log-rank test were utilized to compare TTF after MSR versus prior procedures using the same cohort of patients as their own control group. Subsequent analysis compared TTF after MSR to TTF after 93 other procedures among a second cohort of 18 MS-TN patients not undergoing MSR. BNI pain scores were compared between MSR and other procedures among the MS-TN cohort using a chi-square test.RESULTSTTF was significantly longer after MSR than after other procedures in the MSR cohort (median TTF 79 vs 10 months, respectively, p < 0.0001). Similarly, TTF was longer after MSR than after prior procedures in the non-MSR cohort (median TTF 79 vs 13 months, respectively, p < 0.001). MSR resulted in a higher proportion of excellent pain scores when compared to other procedures in the non-MSR cohort (77% vs 29%, p < 0.001). Probability of treatment survival was higher after MSR than after other procedures at all time points (3, 6, 12, 24, 36, and 48 months). There were no deaths or major complications after MSR.CONCLUSIONSTTF was significantly longer following MSR compared to prior procedures in MS-TN patients. Additionally, a higher proportion of patients achieved excellent BNI pain scores after MSR.

Is there a correlation between clinic-pathological features, MSI, PD-L1 and survival outcomes in resected gastric cancer? Looking for optimal biomarkers.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15566-e15566
Author(s):  
Margherita Ratti ◽  
Nicola Valeri ◽  
Jens Claus Hahne ◽  
Andrea Lampis ◽  
Michele Ghidini ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Rank Test ◽  
Survival Outcomes ◽  
Pathological Features ◽  
Chi Square ◽  
Tissue Samples ◽  
Prognostic Effect ◽  
Kaplan Meier ◽  
Chi Square Test ◽  
Msi Analysis

e15566 Background: Identification of prognostic biomarkers for gastric cancer (GC) patient selection is compelling to improve survival outcomes. Microsatellite instability (MSI) is related with a positive prognostic effect in GC, whereas perioperative chemotherapy resulted detrimental in this subgroup. In metastatic GC, immunotherapy with anti-PD1/PD-L1 drugs has shown promising results. Nevertheless, in early stages, data on the relation between MSI, clinic-pathological features, PD-L1 expression and overall survival (OS) remains sparse, especially in Western population. In our study, the prognostic role of MSI, clinic-pathological features and PD-L1 expression in a cohort of Italian GC patients was examined. Methods: CP data of 148 consecutive stage I-III GC pts resected in Cremona Institute between 2010 and 2014 (mostly chemo and/or radio-naive) were collected. MSI analysis was performed on tissue samples for all cases by polymerase chain reaction. PDL-1 expression, evaluated by immunohistochemistry, was assessed in MSI group. Differences between subgroups were evaluated with Chi-square test; Kaplan-Meier method and Long Rank test were used to calculate OS. Results: Female sex (p=0.012), earlier TNM stages (p=0.011) and limited nodal involvement (p=0.29) significantly correlated with MSI status. MSI is significantly associated with better prognosis, exhibiting an advantage of 28.6 months in OS compared with microsatellite stable subgroup (p<0.001). Most MSI patients expressed PD-L1. MSI patients without PD-L1 expression showed higher percentage of clinical features correlated with better prognosis compared with PD-L1 expressing MSI patients and MSS subgroup. Conclusions: MSI is an independent prognostic biomarker in GC and identifies a subset of patients with better OS and specific clinic-pathological features, including high percentage of PD-L1 expression. MSI could represent a promising biomarker to select patients for chemotherapy versus immunotherapy in non-metastatic disease.

Predictors of immunotherapy (IO) response in hepatocellular carcinoma (HCC).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 555-555
Author(s):  
Samantha Ann Armstrong ◽  
Bhavana Pendurthi Singh ◽  
Monika Kulasekaran ◽  
Petra Prins ◽  
Aiwu Ruth He
Keyword(s):  
Progression Free Survival ◽  
Viral Etiology ◽  
Chi Square ◽  
Steroid Use ◽  
Kaplan Meier ◽  
Best Response ◽  
Chi Square Test ◽  
Grade 3 ◽  
Student’S T ◽  
Multifocal Disease

555 Background: Despite advances in understanding the molecular pathways of HCC, therapeutic options are limited and patient survival is dismal. IO is a promising HCC treatment. There are currently no indicators to identify which patients (pts) will have a prolonged response. Methods: In this single-institutional retrospective analysis, pts received one of five IO containing regimens with nivolumab, pembrolizumab, atezolizumab plus bevacizumab, durvalumab or cemiplimab until disease progression (PD) or unacceptable toxicity. Relevant factors including: stage, viral etiology, vascular invasion (VI), tumor thrombus (TT), multifocal disease, toxicity grade, steroid use for IO mediated toxicities and derived Neutrophil-to Lymphocyte ratio (dNLR), were correlated to clinical outcome: progression free survival (PFS), overall survival (OS), response rate (RR), using Pearson’s chi-square test or student's t-test . Responses were assessed using RECIST v 1.1 criteria for stable disease (SD), partial response (PR) and PD were correlated with best response and PFS. OS was calculated by the Kaplan-Meier method. Results: Cohort demographics (n = 76) were: 72% male; 38% African American, 30% Caucasian and 16% Asian; 29% of pts had HBV, 41% had HCV, 1% had both HBV/HCV and 13% had no viral etiology (n = 64). The majority of pts were stage III (43%) or IV (38%). At the start of IO, 32% had VI, 32% had TT and 80% had multifocal or metastatic disease. 65% of pts experienced IO toxicity, with 24.3% at grade 3 or higher, and 34% requiring steroids. Best response to IO was SD in 65.7% of pts, PR in 25.7% and PD in 8.6%. Median OS was 13m (95% CI 7.9-18.1) from the start of IO and median PFS (n = 65) was 14m (95% CI 6.8-21.2). Median OS and PFS were significantly improved in pts with PR compared to PD (45 vs 8m, p < 0.0005, PFS 15 vs 3m p = 0.007). Both OS and PFS showed benefits for SD of ≥2 months compared to those with PD (11 vs 8m, p < .0005, PFS 5 vs 3m p = .007). VI, TT, stage, viral etiology, toxicity grade or dNLR did not correlate with OS, PFS and RR, however need of steroid treatment trended toward worse outcome. Conclusions: PR and SD are independent predictors for prolonged PFS and OS in HCC pts receiving IO therapy. Absence of steroid use for toxicity trended toward improved IO response.

scholarly journals MicroRNA-124 alone might represent an indicator signifying cholangiocarcinoma prognosis

2020 ◽  
Author(s):  
Ning Wang ◽  
Yanni Li ◽  
Yanfang Zheng ◽  
Huoming Chen ◽  
Xiaolong Wen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Prognostic Biomarker ◽  
Prognostic Indicator ◽  
Rank Test ◽  
Chi Square ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Chi Square Test ◽  
Polymerase Chain

Abstract Background: Previous studies have demonstrated that microRNAs (miRNAs) played a crucial role in various diseases, including cancers. The aim of the study was to evaluate the clinical significance of miR-124 in patients with cholangiocarcinoma (CCA).Methods: The expression pattern of miR-124 was detected in CCA tissues using quantitative reserve transcription polymerase chain reaction (qRT-PCR). The correlation of miR-124 expression with clinicopathological features and overall survival of patients were explored using chi-square test, Kaplan-Meier methods and Cox regression analyses.Results: The miR-124 expression level was strong down-regulated in CCA tissues compared with normal para-cancerous tissues (P<0.001). Moreover, aberrant miR-124 expression was significantly associated with differentiation (P=0.045) and lymph node metastasis (P=0.040). In addition, Kaplan-Meier method and log-rank test revealed that patients with low miR-124 expression has a poorer overall survival compared with those with high miR-124 expression (P=0.002). Furthermore, multivariate analysis confirmed that miR-124 expression (P=0.006; HR=2.006; 95%CI: 1.224-3.289) was an independent prognostic indicator in CCA.Conclusions: Collectively, our results defined miR-124 expression plays important roles in CCA patients. MiR-124 expression might used as a valuable prognostic biomarker for patients with CCA.

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