Clinical Assessment Of Prognosis Research Articles

Apolipoprotein E is a Potential Biomarker for Predicting Cancer Prognosis and is Correlated with Immune Infiltration.

Apolipoprotein E (APOE) is a polymorphic protein that plays a role in lipoprotein transformation and metabolism. It is involved in numerous physiological processes within the body and is closely associated with tumor growth and metastasis. However, the role of APOE in pan-cancer has yet to be evaluated. Therefore, studying the association between APOE and various cancer types is crucial for providing a basis for individualized treatment strategies and clinical prognosis assessment. We investigated the diagnostic and prognostic significance of APOE across 33 tumor types, as well as its correlation with tumor mutation burden (TMB) and microsatellite instability (MSI). Additionally, we employed the ESTIMATE and CIBERSORT algorithms to analyze the potential impact of APOE on the immune system. Furthermore, gene set enrichment analysis (GSEA) was conducted to explore its underlying physiological function. Based on observations from a pan-cancer dataset, APOE expression was significantly different between cancer and normal tissues, and was simultaneously associated with survival outcomes in terms of cancer type, clinical annotation, TMB, MSI, and TICs abundance. In addition, the results also showed that expression of APOE may respond to a variety of cancer chemotherapy. The findings from this study strongly indicate a close association between APOE and tumor development. Moreover, APOE shows promise as a potential biomarker for predicting prognosis and response to immunotherapy in patients with pan-cancer.

Identification and integration analysis of a novel prognostic signature associated with cuproptosis-related ferroptosis genes and relevant lncRNA regulatory axis in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a highly prevalent malignancy worldwide, and its clinical prognosis assessment and treatment is a major research direction. Both ferroptosis and cuproptosis are novel forms of cell death and are considered to be important factors involved in cancer progression. To further understand the correlation between the cuproptosis-related ferroptosis genes (CRFGs) and the prognosis of LUAD, we explore the molecular mechanisms related to the development of the disease. We constructed a prognostic signature containing 13 CRFGs, which, after grouping based on risk score, revealed that the LUAD high-risk group exhibited poor prognosis. Nomogram confirmed that it could be an independent risk factor for LUAD, and ROC curves and DCA validated the validity of the model. Further analysis showed that the three prognostic biomarkers (LIFR, CAV1, TFAP2A) were significantly correlated with immunization. Meanwhile, we found that a LINC00324/miR-200c-3p/TFAP2A regulatory axis could be involved in the progression of LUAD. In conclusion, our report reveals that CRFGs are well correlated with LUAD and provide new ideas for the construction of clinical prognostic tools, immunotherapy, and targeted therapy for LUAD.

Correlative Assessment of p53 Immunostaining Patterns and TP53 Mutation Status by Next-Generation Sequencing in High-Grade Endometrial Carcinomas.

TP53 mutations are frequently identified in the copy number-high molecular subgroup of endometrial carcinomas (ECs). P53 immunohistochemistry (IHC) is a widely used surrogate marker reflecting the mutational status of TP53 , and recent reports have shown ~95% concordance between the two methods in ECs. While these results are promising, studies evaluating the correlation between different p53 IHC staining patterns and comprehensive next-generation sequencing results are still limited. We compared the p53 IHC staining patterns, scored as wild-type, diffuse nuclear overexpression, null/complete absence, and cytoplasmic, to next-generation sequencing results reported by FoundationOneCDx in 43 high-grade ECs: 20 serous ECs, 9 mixed ECs with a serous component, 4 carcinosarcomas with a serous component, and 10 grade 3 endometrioid ECs. The concordance of p53 IHC and TP53 mutation status was 100% (43/43) overall, including 100% (33/33) concordance in tumors with a serous component and 100% (10/10) in endometrioid ECs. Among the 35 tumors with aberrant p53 expression the most commonly observed pattern was diffuse nuclear overexpression seen in 69% (24/35), followed by cytoplasmic staining in 17% (6/35), and complete absence of staining (null) in 14% (5/35) of tumors. Of the 6 tumors with cytoplasmic staining, 4 corresponded to missense mutations within the DNA binding domain (V157F in 2 tumors, and S127P and R280S, in 2 tumor each), while 2 corresponded to nonsense mutations in the tetramerization domain (p.E339*). Our results further support that p53 IHC can serve as an accurate predictor of TP53 alterations in ECs to aid the molecular-based tumor classification and the distinction between tumor histotypes, both of which play an important role in the assessment of clinical prognosis and therapeutic decision making. In addition, our data suggest, that the type and position of TP53 mutation may not directly correlate with the observed p53 IHC pattern in all tumors, and that there may be alternative mechanisms for cytoplasmic localization (other than mutations involving the nuclear localization domain), possibly due to conformational changes or posttranslational modifications of the aberrant p53 protein.

N6-methyladenosine-related microRNAs risk model trumps the isocitrate dehydrogenase mutation status as a predictive biomarker for the prognosis and immunotherapy in lower grade gliomas.

Aim:Lower grade gliomas [LGGs; World Health Organization (WHO) grades 2 and 3], owing to the heterogeneity of their clinical behavior, present a therapeutic challenge to neurosurgeons. The aim of this study was to explore the N6-methyladenosine (m6A) modification landscape in the LGGs and to develop an m6A-related microRNA (miRNA) risk model to provide new perspectives for the treatment and prognostic assessment of LGGs.Methods:Messenger RNA (mRNA) and miRNA expression data of LGGs were extracted from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. An m6A-related miRNA risk model was constructed via least absolute shrinkage and selection operator (LASSO), univariate, and multivariate Cox regression analysis. Next, Kaplan-Meier analysis, principal-component analysis (PCA), functional enrichment analysis, immune infiltrate analysis, dynamic nomogram, and drug sensitivity prediction were used to evaluate this risk model.Results:Firstly, six m6A-related miRNAs with independent prognostic value were selected based on clinical information and used to construct a risk model. Subsequently, compared with low-risk group, LGGs in the high-risk group had a higher m6A writer and reader scores, but a lower eraser score. Moreover, LGGs in the high-risk group had a significantly worse clinical prognosis than those in the low-risk group. Simultaneously, this risk model outperformed other clinicopathological variables in the prognosis prediction of LGGs. Immune infiltrate analysis revealed that the proportion of M2 macrophages, regulatory T (Treg) cells, and the expression levels of exhausted immune response markers were significantly higher in the high-risk group than in the low-risk group. Finally, this study constructed an easy-to-use and free dynamic nomogram to help clinicians use this risk model to aid in diagnosis and prognosis assessment.Conclusions:This study developed a m6A-related risk model and uncovered two different m6A modification landscapes in LGGs. Moreover, this risk model may provide guidance and help in clinical prognosis assessment and immunotherapy response prediction for LGGs.

Endometrial cancer: a genetic point of view.

BackgroundEndometrial cancer is the fourth most frequent gynecological cancer and the most frequent type of uterine cancer. There is an increase in the incidence and mortality of uterine cancers in the past few decades, and there are no well-established screening programs for endometrial cancer currently. Most endometrial cancers arise through the interplay of familial, genetic, and lifestyle factors. Although a number of genetic factors modify endometrial cancer susceptibility, they are not of standard use in the clinical assessment of prognosis. We conducted a comprehensive systematic literature review to provide an overview of the relationship between genetic factors and risk for endometrial cancer.MethodsMEDLINE and EMBASE databases were searched for studies between January 2010 to March 2020 reporting the genes associated with endometrial cancer.ResultsThrough the selection process, we retrieved 186 studies comprising 329 genes identified using several molecular methodologies in all human chromosomes and in mitochondrial DNA. Endometrial cancer exhibits a molecular complexity and heterogeneity coherent with its clinical and histologic variability. Improved characterization of molecular alterations of each histological type provides relevant information about the prognosis and potential response to new therapies.ConclusionsThe current challenge is the integration of clinicopathologic and molecular factors to improve the diagnosis, prognosis, and treatment of endometrial cancer.

Clinical efficacy of intensity-modulated radiotherapy in treatment of 66 patients with intermediate risk localized prostate cancer

Objective To evaluate the clinical efficacy and adverse events of intensity-modulated radiotherapy (IMRT) in the treatment of intermediate risk localized prostate cancer, and analyze the significance of prostate-specific antigen (PSA) level changes. Methods Clinical data of 66 patients with intermediate risk localized prostate cancer admitted to our hospital between 2007 and 2018 were retrospectively analyzed. Sixty patients were treated with endocrine therapy before radiotherapy. The radiation field covered the pelvic lymph node drainage area in 6 cases. Forty-seven patients received image-guided radiotherapy (IGRT). The median dose in the prostate and seminal vesicle was 78 Gy and 48 Gy in the pelvic lymph node drainage area. The survival rate was calculated using the Kaplan-Meier method. Results The median age was 77 years. The median follow-up time was 71.3 months. The 5-year sample size was 47. The 3-and 5-year overall survival (OS) was 98% and 90%.The 3-and 5-year cancer-specific survival (CSS) was 100% and 93%.The 3-and 5-year biochemical relapse-free survival was 97% and 86%.The mean time of PSA declining to the nadir was 5.83 months. The median level of PSA nadir was 0.06 ng/ml after IMRT. The incidence of grade I and Ⅱ early adverse events in the urinary system was 38% and 6%. The incidence of grade I and Ⅱ early adverse events in the gastrointestinal system was 21% and 3%. The incidence of grade I and Ⅱ advanced-stage adverse events in the urinary system was 9% and 2%. The incidence of grade I advanced-stage adverse events in the gastrointestinal system was 5%. Conclusions IMRT yields high clinical efficacy in the treatment of intermediate risk localized prostate cancer with a low risk of adverse events in the early and advanced stage. The monitoring of PSA after IMRT contributes to the assessment of clinical prognosis. Key words: Prostate neoplasm/radiotherapy; Treatment outcome; Prostate-specific antigen

P154 Clinical assessment of prognosis and the prognostic factors in intestinal Bahcet’s disease

P154 Clinical assessment of prognosis and the prognostic factors in intestinal Bahcet’s disease

Hydroxyapatite-coated implant: Clinical prognosis assessment via a retrospective follow-up study for the average of 3 years.

PURPOSEThis research evaluated clinical outcomes of two types of hydroxyapatite (HA)-coated implants: OT (Osstem TS III-HA, Osstem implant Co., Busan, Korea) and ZM (Zimmer TSV-HA, Zimmer dental, Carlsbad, USA).MATERIALS AND METHODSThe research was conducted on 303 implants (89 of OT, 214 of ZM), which were placed from January 16, 2010 to December 20, 2012. The prognosis was evaluated in terms of success rates, survival rates, annual marginal bone loss, and implant stability quotients (ISQ). The samples were classified into immediate, early, conventional, and delayed groups according to the loading time.RESULTSOverall, there were no significant differences between OT and ZM in success rates, survival rates, and annual marginal bone loss, except for the result of secondary stability. OT showed 77.83 ± 8.23 ISQ, which was marginally higher than 76.09 ± 6.90 ISQ of ZM (P<.05). In terms of healing periods, only immediate loading showed statistically significant differences (P<.05). Differences between OT and ZM were observed in terms of two indices, the annual marginal bone loss (0.17 ± 0.58 mm/year < 0.45 ± 0.80 mm/year) and secondary stability (84.36 ± 3.80 ISQ > 82.48 ± 3.69 ISQ) (P<.05). OT and ZM did not have any statistically significant differences in early, conventional, and delayed loading (P>.05).CONCLUSIONOT (97.75%) and ZM (98.50%) showed relatively good outcomes in terms of survival rates. In general, OT and ZM did not show statistically significant differences in most indices (P>.05), although OT performed marginally better than ZM in the immediate loading and 1-stage surgery (P<.05).

Analysis of indicators for clinical prognosis of the patients with heat stroke

Objective To investigate and discuss the values of several common clinical biomarkers in assessment of clinical prognosis in patients with heat stroke. Methods Thirty-one patients with heat stroke suffering less than 24 hours treated in our department from July 2008 to September 2014 were enrolled in this study. They were divided into the survival group and death group according to clinical prognosis and then the differences in values of several common clinical biomarkers for assessment of clinical prognosis in patients with heat stroke were compared between two groups using ROC curve analysis. Results ROC areas under the curve (AUC) of body temperature, lactate dehydrogenase (LDH-L), prothrombin time (PT) and international normalized ratio (INR) at admission were 0.808(0.617-0.998), 0.831 (0.686-0.975), 0.831(0.679-0.982) and 0.831(0.673-0.989), respectively in prediction of deaths in patients with heat stroke and the optimal diagnostic thresholds were 38.65 ℃, 892 U/L, 16.7s and 1.445, respectively. The ROC AUC of survival in patients with heat stroke predicted by Glasgow Coma Scale and fibrinogen (FIB) were 0.815(0.664-0.967) and 0.885(0.746-1.00) respectively and the optimal diagnostic thresholds were 4.5 points and 2.11 g/L. Compared with survival group, in the death group, the admission body temperature group was significantly increased (39.4±1.3 vs. 37.8±1.1 ℃, P=0.01), the admission PT was significantly prolonged[ (24.1±9.5) s vs. (17.0±5.2)s, P=0.021], the INR was significantly elevated[ (2.35±1.25) g/Lvs.(1.46±0.63)g/L, P=0.022], and FIB was significantly decreased[ (1.92±0.58) vs.(3.18±1.04), P=0.014]. There were no significantly statistical differences in other biomarkers, including APACHE Ⅱ Score, Glasgow Coma Scale, 24-hour body temperature, 24-hour temperature decline, LDH-L (U/L), creatine kinase (U/L), PT of activate part, lactic acid (mmol/L) and creatinine (μmol/L) at admission. Conclusions Body temperature, LDH-L, PT, INR, FIB and Glasgow Coma Scale at admission can effectively predict clinical prognosis of the patients with heat stroke. Key words: Heat stroke; Clinical indexes; Predictive values

Red cell distribution width: the crystal ball in the hands of intensivists?

Critically ill patients admitted to intensive care unit (ICU) are at a high risk of morbidity and mortality (1), with significantly increased medical costs. In the meanwhile, intensive care resources are limited, especially in developing countries such as China (2). As a result, rational allocation of limited intensive care resources to those patients who are more likely to benefit from intensive care may depend upon the accurate assessment of clinical prognosis. Therefore, many investigators have developed different prognostic tools, in the form of single parameter, composite indices, and even complicated scores (3-5), in order to assess the severity of illness, predict prognosis, or benchmarking different ICUs. Despite all these efforts, ideal prognostic tools are still lacking, so that investigators are trying to explore new prognostic indices that prove to be accurate, cheap, and readily available.

Prominin-1 and Its Role in Tumor Progression and Assessment of Clinical Prognosis in Systemic Malignancies

To the Editor: The recent article by Di Bonito et al. [1] provided for highly stimulating reading. Prominin-1 may influence tumor progression and clinical prognosis in a number of other systemic tumors. A similar relationship is seen in colorectal cancers. In fact, prominin-1 exerts significant influence on tumor progression in colonic malignancies. Nearly, 36% of all malignant colonic masses are positive for prominin-1 expression [2]. Decreased “overall survival” is seen in patients with up-regulated prominin-1 levels. Accentuated prominin-1 expression is associated with accentuated tumor invasiveness. In general, “microsatellite instability-high” tumors express lower levels of prominin-1 in contrast to “microsatellite stable” colorectal tumors [3]. Not surprisingly, only 9% of colorectal tumors with a good prognosis are positive for prominin-1. In contrast, nearly 52% of colorectal malignancies that exhibit a poor clinical outcome are positive for prominin-1. Lymph node metastasis is also more prominent in tumors positive for prominin-1. Interestingly, the expression of prominin-1 by malignant colonic tissue is decreased following preoperative treatment with nonsteroidal anti-inflammatory agents [4]. Prominin-1 expression also plays a role in tumor progression in prostatic malignancies. For instance, tumor cells that are positive for prominin-1 expression tend to proliferate at a significantly more accentuated rate in comparison to prom inin-1 negative cancer cells [5,6]. Not surprisingly, tumor cells in the G-2 phase are primarily composed of prominin-1 positive cells. A similar association is seen in ovarian malignancies. Nearly 31% of all ovarian cancers are positive for prominin-1 expression. A poor clinical prognosis is seen in patients with ovarian tumors with accentuated prominin-1 expression as is reflected in the shorter “disease-free survival” times noted in these patients [7]. The above examples illustrate the significant role that prom inin-1 plays in tumor progression and its potential use as a significant prognostic maker.

Clinical and Genetic Aspects of Sporadic Non-Medullar Thyroid Cancer

The role of somatic mutations in sporadic thyroid cancer is unclear today. Probably they coming out as aetiological factors in carcinogenesis as well as, respectfully to many authors, can to participate in TC pathogenesis and to determine the clinical course and prognosis of the disease. For today as main oncogenes taking part in initiation of thyroid malignant tumors are considered: RET/PTC, TRK, PTEN, P53, RAS, MET, PPARγ. By means of genetic investigations scientists are trying to solve problems with thyroid cancer differentiated diagnostics (cytokeratin-19, cytokeratin-20, mesothelial cells antigen (Hector Battifora MEsotelial (cell) or HBME-1), loss of heterozigitoty (LOH) in short arm of 3 chromosome (gene VHL -von Hippel Lindau, 3р26). Recently in foreign literature appeared reports of activated mutations in gene BRAF which most frequently are occurred in melanoma and papillary TC. Prognosis of thyroid cancer may reflected by the LOH as a biological breakage as well as changes of tumor suppressive gene P53 which fraught with decrease of disease prognosis. Thus, both researchers and clinicians have many questions concerning the role of genome, particularly in order to precise of genetic abnormality influence on tumor growth and therefore for assessment of clinical prognosis and with aim to chose adequate treatment tactic in each case.

Clinical predictors of response in metastatic germ cell tumors

Twenty-two patients with bulky, metastatic germ cell tumors were treated with cyclophosphamide, vinblastine, dactinomycin, bleomycin, and cisplatin (VAB) alternating with VP-16 and vincristine (VV). The overall complete response rate after chemotherapy with or without surgical excision of residual tissue was 63% (14 of 22 patients) with a median survival of 46 months. Five patients are dead of disease progression and three are alive beyond 3 years with only residual radiographic abnormalities. A retrospective analysis of prognostic variables (numbers of sites of disease, tumor marker levels) using two previously published prognosis formulas demonstrated a good correlation between prognostic variables (numbers of sites of disease, tumor marker levels) and the clinical assessment of prognosis based on tumor bulk and tumor marker level. Nevertheless, individual patients with other, unknown prognostic features may be incorrectly evaluated using either established formulas or clinical assessment of tumor bulk.

劇症肝炎の予後判別の検討

劇症肝炎の予後判別の検討