Construction of immune scores to predict patient prognosis and response of anti-PD1 treatment in stage III-IV melanoma

2020 ◽  
Author(s):  
Wei Li ◽  
Haitao Xiao ◽  
Xuewen Xu ◽  
Yange Zhang
Keyword(s):  
Overall Survival ◽  
Targeted Therapy ◽  
Immune Cell ◽  
Comprehensive Evaluation ◽  
Multivariable Analysis ◽  
Therapy Response ◽  
The Cancer Genome Atlas ◽  
Stage Iii ◽  
Lasso Regression ◽  
Significant Difference

Abstract Background: Tumor-infiltrating immune cells were demonstrated to be associated with patient survival and responses of targeted therapy. However, in melanoma, there is no reliable and individualized prognostic signatures based on comprehensive evaluation of the immune profile inferred from bulk tumor transcriptomes. In this study, we aimed to develop immunoscores associated with prognosis and responses of anti-PD1 targeted therapy in stage III-IV melanoma.Methods: The immunoscore and immunoscore-based prognostic nomogram were constructed based on the melanoma cohort from the Cancer Genome Atlas (TCGA), and validated in the population from the Gene Expression Omnibus (GEO). Besides, in another cohort obtained from the GEO database, we developed an immunoscore for predicting responses of anti-PD1 therapy. Twenty-two types of immune cell fraction were estimated using CIBERSORT. The least absolute shrinkage and selection operator (Lasso) regression model was utilized to develop individualized immunoscores.Results: With the Lasso regression, an immunoscore was constructed consisting of nine types of immune cell subtypes. In both of the training (192 cases) and validation (227 cases) cohorts, significant difference was observed between immunoscore-low and immunoscore-high groups in overall survival (OS). Multivariable analysis demonstrated that the immunoscore was an independent prognostic factor (P < 0.001) for OS. The prognostic value of the immunoscore was also confirmed by the ROC curves. Nomogram integrating immunotype and other clinical characteristics also showed good discrimination, calibration and usability in both of the training and validation cohorts. Finally, in another GEO cohort (218 cases), an immunoscore was constructed based on nine immune cell types for predicting anti-PD1 therapy response. Conclusion: The proposed immunoscores represent promising models for estimating overall survival and anti-PD1 treatment response in patients with stage III-IV melanoma.

scholarly journals Comprehensive Analysis of m6A Regulators Characterized by the Immune Cell Infiltration in Head and Neck Squamous Cell Carcinoma to Aid Immunotherapy and Chemotherapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhiqiang Yang ◽  
Xiaoping Ming ◽  
Shuo Huang ◽  
Minlan Yang ◽  
Xuhong Zhou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Immune Cell ◽  
Comprehensive Evaluation ◽  
Principal Component ◽  
Response To Therapy ◽  
The Cancer Genome Atlas ◽  
Mutation Burden ◽  
Number Variation ◽  
Clinical Benefits ◽  
Cancer Genome Atlas

BackgroundN6-Methyladenosine (m6A), which is a prevalent regulator of mRNA expression, has gathered increasing study interests. Though the role of m6A as being important in many biological processes (such as growth and proliferation of cancers) has been well documented, its potential role in tumor immune microenvironment (TIME) has rarely been analyzed.MethodsWe downloaded RNA expression, single nucleotide polymorphism (SNP), and copy number variation (CNV) data from The Cancer Genome Atlas (TCGA). We then curated 21 m6A regulators and clustered patients into three m6A subtypes and m6A-related gene subtypes and compared them based on overall survival (OS). The combination of CIBERSORT as well as ssGSEA quantified the infiltration levels of immune cells and immune-related functions. The m6A scores were determined by using principal component analysis (PCA) algorithm. Furthermore, we evaluate the correlation of m6A regulators with immune and response to therapy.ResultsThree m6A clusters were identified based on the TCGA-HNSCC cohort, and there were significant associations among them in overall outcomes and caner-related pathways. We found that three m6A clusters were consistent with three phenotypes: immune-inflamed, immune-dessert, and immune-excluded. HNSCC patients were divided into high– and low–m6A score groups based on the cutoff of m6A score. Patients with lower m6A score had better overall survival outcome. Further analysis indicated that patients with higher m6A score presented higher tumor mutation burden (TMB). In addition, patients in low–m6A score subgroup had high chemotherapeutics sensitivity. GEO cohort confirmed patients with low m6A score demonstrated significant overall survival advantages and clinical benefits. Low m6A score carry an increased neoantigen load, eliciting a response to immunotherapy, and its value in predicting survival outcomes of immunotherapy was also confirmed in three anti-PD-1 cohorts.ConclusionsOur study demonstrated that m6A regulators are closely related to TIME and the m6A score was an effective prognostic biomarker and predictive indicator for immunotherapy and chemotherapeutics. Comprehensive evaluation of m6A regulators in tumors will extend our understanding of TIME and effectively guide increasing study investigations on immunotherapy and chemotherapy strategies for HNSCC.

scholarly journals Identification of the angiogenesis related genes for predicting prognosis of patients with gastric cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sheng Zheng ◽  
Zizhen Zhang ◽  
Ning Ding ◽  
Jiawei Sun ◽  
Yifeng Lin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
High Efficiency ◽  
Cox Regression ◽  
Risk Group ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Lasso Regression ◽  
Sequencing Data ◽  
Cox Regression Analysis

Abstract Introduction Angiogenesis is a key factor in promoting tumor growth, invasion and metastasis. In this study we aimed to investigate the prognostic value of angiogenesis-related genes (ARGs) in gastric cancer (GC). Methods mRNA sequencing data with clinical information of GC were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The differentially expressed ARGs between normal and tumor tissues were analyzed by limma package, and then prognosis‑associated genes were screened using Cox regression analysis. Nine angiogenesis genes were identified as crucially related to the overall survival (OS) of patients through least absolute shrinkage and selection operator (LASSO) regression. The prognostic model and corresponding nomograms were establish based on 9 ARGs and verified in in both TCGA and GEO GC cohorts respectively. Results Eighty-five differentially expressed ARGs and their enriched pathways were confirmed. Significant enrichment analysis revealed that ARGs-related signaling pathway genes were highly related to tumor angiogenesis development. Kaplan–Meier analysis revealed that patients in the high-risk group had worse OS rates compared with the low-risk group in training cohort and validation cohort. In addition, RS had a good prognostic effect on GC patients with different clinical features, especially those with advanced GC. Besides, the calibration curves verified fine concordance between the nomogram prediction model and actual observation. Conclusions We developed a nine gene signature related to the angiogenesis that can predict overall survival for GC. It’s assumed to be a valuable prognosis model with high efficiency, providing new perspectives in targeted therapy.

Should All Cases of High-Grade Serous Ovarian, Tubal, and Primary Peritoneal Carcinomas Be Reclassified as Tubo-Ovarian Serous Carcinoma?

2015 ◽  
Vol 25 (7) ◽  
pp. 1201-1207 ◽  
Author(s):  
Esther Louise Moss ◽  
Tim Evans ◽  
Philippa Pearmain ◽  
Sarah Askew ◽  
Kavita Singh ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clear Cell ◽  
Stage Iii ◽  
Serous Carcinoma ◽  
Low Grade ◽  
Type I ◽  
High Grade ◽  
Type Ii ◽  
Ovarian Serous Carcinoma ◽  
Significant Difference

IntroductionThe dualistic theory of ovarian carcinogenesis proposes that epithelial “ovarian” cancer is not one entity with several histological subtypes but a collection of different diseases arising from cells of different origin, some of which may not originate in the ovarian surface epithelium.MethodsAll cases referred to the Pan-Birmingham Gynaecological Cancer Centre with an ovarian, tubal, or primary peritoneal cancer between April 2006 and April 2012 were identified from the West Midlands Cancer Registry. Tumors were classified into type I (low-grade endometrioid, clear cell, mucinous, and low-grade serous) and type II (high-grade serous, high-grade endometrioid, carcinosarcoma, and undifferentiated) cancers.ResultsOvarian (83.5%), tubal (4.3%), or primary peritoneal carcinoma (12.2%) were diagnosed in a total of 583 woman. The ovarian tumors were type I in 134 cases (27.5%), type II in 325 cases (66.7%), and contained elements of both type I and type II tumors in 28 cases (5.7%). Most tubal and primary peritoneal cases, however, were type II tumors: 24 (96.0%) and 64 (90.1%), respectively. Only 16 (5.8%) of the ovarian high-grade serous carcinomas were stage I at diagnosis, whereas 240 (86.6%) were stage III+. Overall survival varied between the subtypes when matched for stage. Stage III low-grade serous and high-grade serous carcinomas had a significantly better survival compared to clear cell and mucinous cases,P= 0.0134. There was no significant difference in overall survival between the high-grade serous ovarian, tubal, or peritoneal carcinomas when matched for stage (stage III,P= 0.3758; stage IV,P= 0.4820).ConclusionsType II tumors are more common than type I and account for most tubal and peritoneal cancers. High-grade serous carcinomas, whether classified as ovarian/tubal/peritoneal, seem to behave as one disease entity with no significant difference in survival outcomes, therefore supporting the proposition of a separate classification of “tubo-ovarian serous carcinoma”.

Analysis of 12 Genes in 268 Cases with CMML Identifies ASXL1 Mutations As the Most Important Genetic Alteration Associated with Adverse Outcome

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3491-3491
Author(s):  
Susanne Schnittger ◽  
Manja Meggendorfer ◽  
Vera Grossmann ◽  
Tamara Alpermann ◽  
Christiane Eder ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adverse Outcome ◽  
Multivariable Analysis ◽  
Melting Curve ◽  
Gene Mutations ◽  
Prognostic Impact ◽  
Mutant Genotype ◽  
Cox Regression Analysis ◽  
Significant Difference ◽  
Equity Ownership

Abstract Abstract 3491 Introduction: Chronic myeloid monocytic leukemia (CMML) has been associated with a high number of somatic mutations in diverse genes and various mutant genotype combinations were observed. The patterns of marker combinations and prognostic impact of single markers are poorly understood. Aims: Comprehensive analysis of the genetic marker profile in a large CMML cohort and evaluation of potential prognostic implications. Patients and Methods: In total, 268 cases with CMML (CMML-1 n=191, CMML-2 n=77) were included. The cohort comprised 186 males and 82 females with a median age of 73.0 yrs (range: 21.9 – 93.3 yrs). In 262 cases cytogenetic data was available: 185 cases (70.6%) had a normal karyotype and 77 (29.4%) showed aberrant karyotypes. Data on mutations were available in all patients for SRSF2, U2AF1, JAK2 V617F, and in subcohorts for: ASXL1 (n=255), CBL (n=267), EZH2 (n=205), KIT D816 (n=263), KRAS (n=260), NRAS (n=266), RUNX1 (n=267), SF3B1 (n=240), and TET2 (n=157). Mutations were analyzed by a combination of amplicon deep-sequencing (Roche 454, Branford, CT), direct Sanger sequencing, real time PCR or melting curve analyses. Analysis for overall survival was restricted to 185 cases with evaluable clinical data (median follow-up: 427 days, median OS: 51%). Results: In total 633 mutations were detected in 268 patients (median: 2 per patient, range 0–7). In CMML-1 the mean number of mutations was equal to CMML-2 (2.38 vs. 2.55, p=n.s.). In detail, the most frequent mutations were detected in TET2 (61.1%; 96/157), followed by SRSF2 (47.8%; 128/268), ASXL1 (44.7%; 144/255), RUNX1 (22.8%; 61/267), CBL (19.1%; 51/267), NRAS (15.4%; 41/266), KRAS (10.8%; 28/260), EZH2 (9.3%; 19/205), JAK2 (6.7%; 18/268), U2AF1 (5.2%; 14/268), SF3B1 (5.0%; 12/240), and KIT (4.2%; 11/263). Impact on survival was tested for all 12 gene mutations. A significant difference in overall survival (OS) was observed only for ASXL1 mut vs ASXL1 wt patients (median OS: 19.4 months vs not reached; p=0.003). None of the other gene mutations showed a significant impact on OS. In a next step mutations from the RAS pathway (NRAS, KRAS, CBL) were combined into one group (n=85) and were analyzed in comparison to all others (n=90). However, no impact on OS was detected. Next, patients with at least one mutation in a gene from the splicing machinery (U2AF1, SRSF2, SF3B1) (n=109) were combined and tested vs all other patients (n=57), however, no prognostic relevance was found. In addition, no difference in outcome was observed between CMML-1 and CMML-2 patients. Of note, the adverse impact of ASXL1 mut was restricted to the CMML-2 subcohort (25 mut, 31 wt, median OS: 17.3 months vs n.r.; p=0.001), whereas there was no effect in CMML-1 pts (59 mut and 54 wt). We also evaluated the cytogenetic risk score introduced by Such et al. (Haematologica 2011) and were not able to find differences in survival (neither pairwise between the respective subgroups, nor overall). However, we were able to show prognostic impact of ASXL1 mut within the cytogenetic risk groups suggested by Such: within the favorable subgroup ASXL1 mut patients (n=56) had worse outcome than ASXL1 wt (n=65) (median 19.4 months vs n.r.; p=0.027). This was true also for the adverse subgroup showing a trend to worse outcome for ASXL1 mut vs ASXL1 wt (n=16 vs n=9; median 17.3 months vs n.r.; p=0.057). No difference was seen between the 9 ASXL1 mut and 8 ASXL1 wt patients within the intermediate risk group. In the univariable cox regression analysis taking age, gender, type dysplastic vs proliferative, CMML-1 vs CMML-2, WBC, hemoglobin (Hb), Such score and ASXL1 mut into account, the following parameters were found to be relevant for outcome: age (p=0.001, HR 1.74 per decade), WBC (p=0.044, HR 1.08 per 10×109/L), Hb (p<0.001, HR 0.70, ASXL1 mut (p=0.004, HR 2.38). These parameters entered the multivariable analysis and age (p=0.005, HR: 1.61 per 10 yrs of increase), Hb (p<0.001 HR 0.704) and mutated ASXL1 status (p=0.009, HR 2.30) were independent prognostic parameters for OS. Conclusion: 1) CMML-1 as well as CMML-2 are genetically complex diseases each showing a high number of mutations. 2) One of the most frequently mutated genes in both subgroups is ASXL1. 3) ASXL1 is the only one out of 12 genes which is independently associated with adverse outcome. Disclosures: Schnittger: MLL Munich Leukemia Laboratory: Equity Ownership. Meggendorfer:MLL Munich Leukemia Laboratory: Employment. Grossmann:MLL Munich Leukemia Laboratory: Employment. Alpermann:MLL Munich Leukemia Laboratory: Employment. Eder:MLL Munich Leukemia Laboratory: Employment. Kohlmann:MLL Munich Leukemia Laboratory: Employment. Kern:MLL Munich Leukemia Laboratory: Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership.

Prognosis and comorbidities in stage III and IV endometrial cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16553-e16553
Author(s):  
K. Wright ◽  
E. Munro ◽  
M. del Carmen ◽  
A. K. Goodman
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Stage Iv ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Stage Iii ◽  
Rank Test ◽  
Laboratory Values ◽  
Significant Difference ◽  
Baseline Creatinine

e16553 Background: While endometrial cancer may be associated with many comorbid conditions, none have been characterized as changing overall prognosis. The aim of this study was to identify medical conditions or laboratory values, that may serve as prognostic factors in stage III and IV endometrial cancer. Methods: A retrospective chart review identified 112 women with stage III or IV endometrial cancer between years 1993–1998. Information about medical comorbidities and presenting lab values were collected using electronic medical records. Progression free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier survival method and the log rank test. Results: The average age was 64.9 yrs. 79 women (70.5%) had stage III disease and 33 women (29.5%) had stage IV disease. For those with a baseline creatinine <1.2 (n = 91), the PFS and OS were not significantly different from those with a baseline creatinine ≥1.2 (n = 17; p = 0.554 and p = 0.487, respectively). There was a non-significant trend toward worse PFS for the 41 patients with hypertension (HTN) compared to the 62 without (48.0 and 61.2 months, p = 0.191). The overall survival was significantly worse for those with HTN (38.7 months vs. 56.0 months p = 0.046). For those with known coronary artery disease, no significant difference in PFS or OS was found (p = 0.792 and p = 0.312 respectively). Those with diabetes (n = 15) did not have a significantly different PFS compared to those who did not (n = 88; p = 0.728). The OS was worse at 20.1 months for those with diabetes compared to 54.3 months for those without (p = 0.001). Baseline albumin had a significant effect on both PFS and OS. Those with an albumin <3.5 (n = 54) had a PFS of 46.2 months compared to 94.0 months for those with an albumin ≥3.5 (n = 23; p = 0.007), and the OS for those with low albumin was 44.8 months compared to 83.4 months for those with the higher albumin (p = 0.005). Conclusions: These results suggest that past medical history and some baseline laboratory values may be important in considering prognosis. In particular, patients with a history of HTN or diabetes have a worse overall survival. Those with a baseline albumin of <3.5 have a worse PFS and OS. No significant financial relationships to disclose.

Brain metastases in patients treated with targeted therapy for metastatic renal cell carcinoma (mRCC).

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 326-326
Author(s):  
H. Alharbi ◽  
T. K. Choueiri ◽  
C. K. Kollmannsberger ◽  
S. North ◽  
M. J. MacKenzie ◽  
...  
Keyword(s):  
Overall Survival ◽  
Targeted Therapy ◽  
Brain Metastases ◽  
Treatment Time ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Local Treatment ◽  
Multivariable Analysis ◽  
First Line ◽  
The Brain

326 Background: Patients with brain metastases from advanced RCC treated in the targeted therapy era are not well characterized. Methods: Data from patients with mRCC treated with targeted therapy were collected through the International mRCC Database Consortium from 6 centers. Results: One hundred six out of 705 (15%) patients with mRCC had brain metastases. Forty-seven patients had brain metastases at the start of first-line anti-VEGF therapy and the rest developed metastases during follow-up. Of the patients with brain metastases, 6%, 68%, and 26% were in the favorable, intermediate and poor prognosis groups, respectively, per the Heng et al JCO 2009 criteria. Ninety percent had cerebral metastases, 17% had cerebellar metastases, 40% had a Karnofsky performance status (KPS) <80%, and 81% had symptoms of brain metastases. The median largest size and number of brain metastases was 1.8 cm (range 0.2–6.6) and 1 (range 1–20), respectively. Patients were treated with first-line sunitinib (n=77), sorafenib (n=23), bevacizumab (n=5), and temsirolimus (n=1). Local disease treatment included whole brain radiotherapy (81%), stereotactic radiosurgery (25%), and neurosurgery (25%). The brain metastases of 59 patients were evaluable and based on the local treatment and/or targeted therapy achieved 7 (12%) complete responses, 23 (39%) partial responses, 14 (24%) patients with stable disease, and 15 (25%) patients with progressive disease in the brain metastases. Patients with more than 4 brain metastases vs. those with no more than 4 have an overall survival time from diagnosis of brain metastasis of 3.9 vs. 15.4 months (p=0.0051). Previous nephrectomy, sarcomatoid, and non-clear cell histology are not associated with development of brain metastases. On multivariable analysis, KPS<80% (p=0.0139), diagnosis to treatment with targeted therapy <1 year (p=0.0012), and higher number of brain metastases (p=0.0311) were associated with worse survival from diagnosis of brain metastases. Conclusions: In patients with brain metastases from RCC, KPS at start of therapy, diagnosis to treatment time and number of brain metastases may be prognostic factors for overall survival. [Table: see text]

The role of adjuvant chemotherapy in the management of surgically resected primary pulmonary salivary gland-type carcinomas.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21009-e21009
Author(s):  
Moustafa Younis ◽  
Sunpreet Rakhra ◽  
Kevin F Kennedy ◽  
Jessica K Heimes ◽  
John Russell Davis ◽  
...  
Keyword(s):  
Overall Survival ◽  
Salivary Gland ◽  
Adjuvant Chemotherapy ◽  
Surgical Resection ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Tumor Type ◽  
Significant Difference ◽  
Gland Type

e21009 Background: Primary pulmonary salivary gland-type carcinomas (PSGC) are rare tumors. There are limited data on the role of adjuvant chemotherapy after surgical resection of these tumors. Here, we examine the role of adjuvant chemotherapy in the management of resected PSGC. Methods: The National Cancer Database was queried to identify patients with PSGC who underwent surgical resection. Histology codes 8200- adenoid cystic carcinoma (ACC), 8430- mucoepidermoid carcinoma (MEC), 8550- acinic cell carcinoma (AIC) and 8551- adenocarcinoma, acinar predominant were used. Patients were divided based on chemotherapy status. Summary and univariate analysis was performed. Multivariable proportional hazard regression analyses were used to obtain hazard ratios (HR). Results: A total of 6685 patients, with a mean (±SD) age of 66.1 ± 11.0 years, were included; 4148 (62%) were females. Most patients were Caucasian (84%). Chemotherapy was administered in 1141 patients (17%); multiagent chemotherapy: n = 1034 (91%). AIC was the most common subtype (n = 6302, 94%) followed by MEC (n = 304, 4.6%) and ACC (n = 73, 1.1%). Patients who received chemotherapy were younger (64.0 ± 9.0 vs 66.5 ± 11.3; p < 0.001), otherwise, there was no significant difference in baseline demographics. Unadjusted 5-year survival for stage I PSGC was significantly lower in the chemotherapy arm (60.5% vs 72%, p < 0.001). Chemotherapy did not improve survival in resected stage II or III PSGC. Overall survival was inferior with chemotherapy on multivariable analysis (adjusted HR: 1.32, 95%CI (1.13-1.55), p = 0.0006). Older age, male gender, positive margins, higher clinical stage, comorbidities, rural population and pneumonectomy were associated with lower overall survival (Table). Conclusions: Contrary to previous studies AIC is the most common tumor type among PSGC. Adjuvant chemotherapy is associated with worse survival in resected PSGC and current guidelines for administering adjuvant chemotherapy in resected lung cancer is inadequate for this population. [Table: see text]

scholarly journals Stratification of chemotherapy-treated stage III colorectal cancer patients using multiplexed imaging and single-cell analysis of T-cell populations

2021 ◽  
Author(s):  
Xanthi Stachtea ◽  
Maurice B. Loughrey ◽  
Manuela Salvucci ◽  
Andreas U. Lindner ◽  
Sanghee Cho ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Single Cell ◽  
Immune Cell ◽  
Single Cell Analysis ◽  
Cell Types ◽  
Cell Segmentation ◽  
Stage Iii ◽  
Cell Analysis ◽  
Increased Risk

AbstractColorectal cancer (CRC) has one of the highest cancer incidences and mortality rates. In stage III, postoperative chemotherapy benefits <20% of patients, while more than 50% will develop distant metastases. Biomarkers for identification of patients at increased risk of disease recurrence following adjuvant chemotherapy are currently lacking. In this study, we assessed immune signatures in the tumor and tumor microenvironment (TME) using an in situ multiplexed immunofluorescence imaging and single-cell analysis technology (Cell DIVETM) and evaluated their correlations with patient outcomes. Tissue microarrays (TMAs) with up to three 1 mm diameter cores per patient were prepared from 117 stage III CRC patients treated with adjuvant fluoropyrimidine/oxaliplatin (FOLFOX) chemotherapy. Single sections underwent multiplexed immunofluorescence staining for immune cell markers (CD45, CD3, CD4, CD8, FOXP3, PD1) and tumor/cell segmentation markers (DAPI, pan-cytokeratin, AE1, NaKATPase, and S6). We used annotations and a probabilistic classification algorithm to build statistical models of immune cell types. Images were also qualitatively assessed independently by a Pathologist as ‘high’, ‘moderate’ or ‘low’, for stromal and total immune cell content. Excellent agreement was found between manual assessment and total automated scores (p < 0.0001). Moreover, compared to single markers, a multi-marker classification of regulatory T cells (Tregs: CD3+/CD4+FOXP3+/PD1−) was significantly associated with disease-free survival (DFS) and overall survival (OS) (p = 0.049 and 0.032) of FOLFOX-treated patients. Our results also showed that PD1− Tregs rather than PD1+ Tregs were associated with improved survival. These findings were supported by results from an independent FOLFOX-treated cohort of 191 stage III CRC patients, where higher PD1− Tregs were associated with an increase overall survival (p = 0.015) for CD3+/CD4+/FOXP3+/PD1−. Overall, compared to single markers, multi-marker classification provided more accurate quantitation of immune cell types with stronger correlations with outcomes.

scholarly journals The Spectrum, Tendency and Predictive Value of PIK3CA Mutation in Chinese Colorectal Cancer Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Xinhui Fu ◽  
Hanjie Lin ◽  
Xinjuan Fan ◽  
Yaxi Zhu ◽  
Chao Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Regression Analysis ◽  
Stage Iv ◽  
Stage Iii ◽  
Wild Type ◽  
Cox Regression Analysis ◽  
Significant Difference ◽  
Exon 9 ◽  
Exon 20

BackgroundPIK3CA is a high-frequency mutation gene in colorectal cancer, while its prognostic value remains unclear. This study evaluated the mutation tendency, spectrum, prognosis power and predictive power in cetuximab treatment of PIK3CA in Chinese CRC cohort.MethodsThe PIK3CA exon 9 and 20 status of 5763 CRC patients was detected with Sanger sequencing and a high-resolution melting test. Clinicopathological characteristics of 5733 patients were analyzed. Kaplan-Meier method and nomogram were used to evaluate the overall survival curve and disease recurrence, respectively.ResultsFifty-eight types of mutations in 13.4% (771/5733) of the patients were detected. From 2014 to 2018, the mutation rate of PIK3CA increased from 11.0% to 13.5%. At stage IV, exon 20 mutated patients suffered shorter overall survival time than wild-type patients (multivariate COX regression analysis, HR = 2.72, 95% CIs = 1.47-5.09; p-value = 0.012). At stage III, PIK3CA mutated patients were more likely to relapse (multivariate Logistic regression analysis, exon 9: OR = 2.54, 95% CI = 1.34-4.73, p = 0.003; exon 20: OR = 3.89, 95% CI = 1.66-9.10, p = 0.002). The concordance index of the nomogram for predicting the recurrence risk of stage III patients was 0.685. After cetuximab treatment, the median PFS of PIK3CA exon 9 wild-type patients (n = 9) and mutant patients (n = 5) did not reach a significant difference (3.6 months vs. 2.3 months, Log-rank test, p-value = 0.513).ConclusionsWe found that PIK3CA mutation was an adverse predictive marker for the overall survival of stage IV patients and recurrence of stage III patients, respectively. Further more, we suggested that PIK3CA exon 9 mutations are not negative predictors of cetuximab treatment in KRAS, NRAS, and BRAF wild-type mCRC patients.

scholarly journals A Novel Ferroptosis-Related lncRNAs Signature Predicts Clinical Prognosis and is Associated with Immune Landscape in Pancreatic Cancer

2021 ◽  
Author(s):  
Haiqin Ping ◽  
Xingqing Jia ◽  
Hengning Ke
Keyword(s):  
Pancreatic Cancer ◽  
Immune Cell ◽  
Pearson Correlation ◽  
The Cancer Genome Atlas ◽  
Lasso Regression ◽  
Clinical Prognosis ◽  
Pathway Enrichment ◽  
Cancer Genome Atlas ◽  
Pearson Correlation Analysis ◽  
Selection Operator

Abstract Pancreatic cancer is one of the most lethal malignancies and currently therapies are severely lacking. In this study, we aimed to establish a novel ferroptosis-related lncRNAs signature to predict the prognosis of patients with pancreatic cancer and evaluate the predictive abilities of candidate lncRNAs. According to The Cancer Genome Atlas (TCGA) database, a total of 182 patients with pancreatic cancer were included in our study. Ferroptosis-related lncRNAs were screened by Pearson correlation analysis with 60 reported ferroptosis-related genes. Through univariate, least absolute shrinkage and selection operator (LASSO) regression and multivariate regression analyses, a novel signature based on five ferroptosis-related lncRNAs(ZNF236-DT, CASC8, PAN3-AS1, SH3PXD2A-AS1, LINP1) was constructed. Risk-related differentially expressed genes (DEGs) were subjected to enrichment analyses for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.The results revealed that that immune cell infiltration, immune-related functions and checkpoints were factors to affect prognoisis of pancreatic cancer. In summary, we identified the prognostic ferroptosis-related lncRNAs in pancreatic cancer and these lncRNAs may serve as therapeutic targets for pancreatic cancer.

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