Independent Poor Prognostic Factor Research Articles

Fat Loss in Patients with Metastatic Clear Cell Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors

The purpose of this study was to determine the prognostic impact of fat loss after immune checkpoint inhibitor (ICI) treatment in patients with metastatic clear cell renal cell carcinoma (ccRCC). Data from 60 patients treated with ICI therapy for metastatic ccRCC were retrospectively analyzed. Changes in cross-sectional areas of subcutaneous fat (SF) between the pre-treatment and post-treatment abdominal computed tomography (CT) images were expressed as percentages and were divided by the interval between the CT scans to calculate ΔSF (%/month). SF loss was defined as ΔSF < -5%/month. Survival analyses for overall survival (OS) and progression-free survival (PFS) were performed. Patients with SF loss had shorter OS (median, 9.5 months vs. not reached; p < 0.001) and PFS (median, 2.6 months vs. 33.5 months; p < 0.001) than patients without SF loss. ΔSF was independently associated with OS (adjusted hazard ratio (HR), 1.49; 95% confidence interval (CI), 1.07-2.07; p = 0.020) and PFS (adjusted HR, 1.57; 95% CI, 1.17-2.12; p = 0.003), with a 5%/month decrease in SF increasing the risk of death and progression by 49% and 57%, respectively. In conclusion, Loss of SF after treatment initiation is a significant and independent poor prognostic factor for OS and PFS in patients with metastatic ccRCC who receive ICI therapy.

Clinical features of idiopathic pleuroparenchymal fibroelastosis with progressive phenotype showing a decline in forced vital capacity

BackgroundIdiopathic pleuroparenchymal fibroelastosis (IPPFE) is heterogeneous, with some patients showing a progressive decline in forced vital capacity (FVC). However, the clinical features of these cases with progressive phenotypes remain unknown. MethodsThis retrospective study included 48 patients diagnosed with IPPFE who underwent longitudinal pulmonary function tests at our institution from 2005 to 2021. The progressive phenotype was defined as a relative decline of ≥10% in %FVC within two years from diagnosis of IPPFE, and its clinical features were evaluated. ResultsOf the 48 patients, 23 (47.9%) were classified as progressive IPPFE. They were significantly older with a higher rate of dyspnea, fine crackles on chest auscultation, lower-lobe usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography, and lower %FVC at diagnosis than non-progressive IPPFE. Additionally, progressive IPPFE had a significantly higher rate of long-term oxygen therapy requirement, the incidence of pneumothorax, and weight loss after diagnosis, which showed worse survival than non-progressive IPPFE. The relative decline in %FVC and weight loss showed a significant positive correlation. Multivariate analysis revealed that lower body mass index tended to predict early progression, and the coexistence of lower-lobe UIP pattern was significantly associated with early progression. A decline in %FVC was an independent poor prognostic factor in IPPFE. ConclusionsWith a progressive decline in %FVC, IPPFE often has an advanced stage at diagnosis and lower-lobe UIP pattern and is associated with weight loss and worse survival.

Smoking is an Independent Marker of Poor Prognosis in Cutaneous Melanoma.

Previous studies have suggested that persistent tobacco smoking impairs survival in cutaneous melanoma, but the effects of smoking and other prognostic factors have not been described in detail. This study examined the association of smoking (persistent, former, or never) with melanoma-specific (MSS) and overall survival (OS) in patients with cutaneous melanoma treated in Southwest Finland during 2005 to 2019. Clinical characteristics were obtained from electronic health records for 1,980 patients. Smoking status was available for 1,359 patients. Patients were restaged according to the 8th edition of the tumour-node-metastasis (TNM) classification. Smoking remained an independent prognostic factor for inferior melanoma-specific survival regardless of age, sex, stage, and comorbidities. The hazard ratio of death from melanoma was 1.81 (1.27-2.58, p = 0.001) in persistent and 1.75 (1.28-2.40, p = 0.001) in former smokers compared with never smokers. In 351 stage IV patients, smoking was associated with increased melanoma-specific and overall mortality: median MSS 10.4 (6.5-14.3), 14.6 (9.1-20.1), and 14.9 (11.4-18.4) months, p = 0.01 and median OS 10.4 (6.5-14.3), 13.9 (8.6-19.2), and 14.9 (11.7-18.1) months, p = 0.01 in persistent, former, and never smokers, respectively. In conclusion, since smoking represents an independent modifiable poor prognostic factor in patients with cutaneous melanoma, smoking habits should be proactively asked about by healthcare professionals, in order to support smoking cessation.

High Expression of CD300A Predicts Poor Survival in Acute Myeloid Leukemia

Introduction: Recent studies have suggested that CD300A was an oncogene in acute myeloid leukemia (AML) development. However, the clinical relevance and biological insight into CD300A expression in AML are still not well understood. The present study aimed to examine the expression characteristics of CD300A in AML and confirmed its clinical significance for AML. Methods: Quantification of the CD300A transcript was performed in 119 AML patients by real-time quantitative PCR in bone marrow blasts. The predictive significance of CD300A expression on the clinical outcomes of AML was assessed using overall survival (OS) and relapse-free survival (RFS). The published Cancer Genome Atlas (TCGA) data were used as an external validation for survival analysis and pathway analyses. Results: In comparison with monocytes from healthy peripheral blood cells, the expression levels of CD300A in AML cells were higher. Patients in the intermediate and adverse risk categories by WHO criteria (2018) had higher CD300A expression levels than those in the favorable risk category (p < 0.001). AML patients with high expression of CD300A had a higher early death rate (p = 0.029), lower complete remission rate (p = 0.042), higher death rate (p < 0.001) and relapse rate (p = 0.002), and shorter OS (p < 0.0001) and RFS (p < 0.0001). Through multivariable analysis, high CD300A expression in AML was also an independent poor prognostic factor. The CAMP and CGMP-PKG signaling pathways may be stimulated by increased CD300A expression levels, which may be important for the development of AML. Conclusions: The expression levels of CD300A were associated with risk stratification and the clinical relevance of AML. High CD300A expression may act as an independent adverse prognostic factor for OS and RFS in AML.

IgG4 expression and IgG4/IgG ratio in the tumour invasion front predict long-term outcomes for patients with intrahepatic cholangiocarcinoma

IgG4-positive plasma cells are reportedly increased in the tumour microenvironment, and a high number of these cells in tumours is a poor prognostic factor in several cancers. However, there are no reported analyses of IgG4 expression in intrahepatic cholangiocarcinoma (ICC). This study aimed to analyse the correlations between prognosis-related clinicopathological features of patients with ICC and IgG4 expression. We identified 37 ICC patients who underwent surgical resection between January 2010 and December 2020. The number of IgG-positive and IgG4-positive plasma cells in the tumour, invasion front, and stroma near the tumour was analysed by immunostaining. Furthermore, we examined the association of prognosis-related clinicopathological data with the number of IgG4-positive plasma cells and IgG4/IgG ratio in ICC patients. The IgG4-positive plasma cell percentages for the intra-tumour area, invasion front, and non-cancerous area (NCA) near the tumour were 91.9%, 56.8%, and 81.1%, respectively. IgG-positive plasma cells were observed in each region for all cases, except for NCA tissue in one case. A high IgG4 expression level and IgG4/IgG ratio in the invasion front were significantly associated with poor overall survival (OS) (log-rank test p=0.0438 and p=0.0338, respectively). Multivariate analysis for OS revealed that high IgG4 expression (p=0.0140), lymph node metastasis (p=0.0205), and positive surgical margin (p=0.0009) or a high IgG4/IgG ratio (p=0.0051), lymph node metastasis (p=0.0280), and positive surgical margin (p=0.0009) were independent poor prognostic factors. In conclusion, a high IgG4 expression level and IgG4/IgG ratio in the invasion front are independent poor prognostic factors for ICC. Targeted therapy for IgG4 may improve the prognosis for patients with ICC.

Distinct role of tumor-infiltrating lymphocytes between synchronous and metachronous colorectal cancer.

Tumor-infiltrating lymphocytes (TILs) may influence the prognosis of colorectal liver metastasis (CRLM). We assessed the prognostic value of evaluating TILs in the primary and metastatic sites of synchronous CRLM as well as metachronous CRLM. We examined 90 patients who underwent curative primary and liver metastasis resection for colorectal cancer. CD8+ TILs (cytotoxic T cells) or CD45RO+ TILs (memory T cells) in both primary and metastatic sites were simultaneously evaluated by immunohistochemistry. Fifty-one patients had synchronous CRLM, and 39 patients had metachronous CRLM. In synchronous cases, the overall survival (OS) was significantly worse in patients with low CD8+ or CD45RO+ TILs in a metastatic site than in those with high CD8+ or CD45RO+ TILs (P = 0.017 and P = 0.005, respectively). Multivariate analysis showed that age ≥ 65years (P = 0.043), maximum tumor size ≥ 30mm (P = 0.003), primary N2-3 (P = 0.019), and low CD8+ TILs in metastatic site (P = 0.046) were independent poor prognostic factors. In contrast, in metachronous cases, OS was significantly worse in patients with low CD45RO+ TILs in a primary site than in those with high CD45RO+ TILs (P = 0.021). CD45RO+ TILs in a primary site (P = 0.044) were determined to be independent prognostic factor on multivariate analysis. The immune microenvironment between synchronous and metachronous CRLM might be different, and these differences may affect its prognosis.

TP53 gain of function mutation as a prognostic factor in high-methylated metastatic colorectal cancer: Translational research of TRICOLORE study.

179 Background: TP53 tumor suppressor gene is frequently inactivated by loss-of-function mutations. Some of the mutations gain additional oncogenic functions and are known as gain-of-function (GOF) mutations. This study analyzed the association among primary tumor site (PS), genome-wide DNA methylation status (GWMS), and TP53 mutation subtypes about prognosis in metastatic colorectal cancer (mCRC). Methods: Tumor tissues of mCRC patients registered in the TRICOLORE Study (clinical trial number) were analyzed for GWMS and TP53 mutation as translational research and were classified into high-methylated colorectal cancer (HMCC) and low-methylated colorectal cancer (LMCC) for GWMS, and wild-type , GOF mutation and non-GOF mutation for TP53 mutation. Overall survival (OS) was compared between single or combined subgroups, and Cox regression analysis was performed to identify factors contributing to OS. Results: A total of 209 patients were analyzed, HMCC and LMCC were 60 (28.7%) and 149 (71.3%), respectively. TP53 wild-type , GOF mutation and non-GOF mutation were 35 (16.7%), 79 (37.8%) and 95 (45.5%), respectively. HMCC showed a significantly worse prognosis than LMCC (median OS 25.3 vs. 40.3 months, P &lt; 0.01, hazard ratio 1.87). Combining GWMS and TP53 mutation subtypes about prognosis, the HMCC/GOF (n = 26) group had a significantly poorer prognosis than the other three groups including HMCC/non-GOF (n = 22), LMCC/GOF (n = 53), and LMCC/non-GOF groups (n = 73) (median OS 17.7, 35.3, 40.3, 41.2 months, p = 0.007, p &lt; 0.001, p &lt; 0.001, respectively). The HMCC/GOF group had a poorer prognosis than the other 3 groups regardless of the PS. In the multivariate analysis in the GOF mutation subgroup, HMCC (p &lt; 0.01) was the only poor prognostic factor, while right-sided colon cancer (p = 0.03) and RAS mutations (p = 0.01) were significant poor prognostic factors in the multivariate analysis in the non-GOF mutation subgroup. Conclusions: TP53 gain of function mutations are independent poor prognostic factors in high-methylated metastatic colorectal cancer.

Preoperative monocyte to high-density lipoprotein ratio as a predictor of survival outcome of gastric cancer patients after radical resection.

Aim: This study aimed to verify the prognostic value of monocyte to high-density lipoprotein ratio (MHR) in gastric cancer patients after radical resection. Methods: The Cox proportional hazards model was used to determine the risk variables for survival. Results: Older age (>60years) (hazard ratio [HR]: 1.832; 95% CI:1.167-2.725; p =0.009), advanced tumor node metastasis stage (p <0.05), lymphatic invasion (HR: 1.639; 95% CI: 1.114-3.032; p <0.05), vascular invasion (HR: 2.002; 95% CI: 1.246-5.453; p =0.028) and high MHR (HR: 1.154; 95% CI: 1.062-2.315; p =0.021) were independent poor prognostic factors for gastric cancer patients after radical resection. Conclusion: Older age, advanced tumor node metastasis stage, lymphatic invasion, vascular invasion and high MHR were independent poor prognostic factors for gastric cancer patients after radical resection.

Expression and Clinical Significance of Eukaryotic Initiation Factor 4E in Newly Diagnosed Patients with Multiple Myeloma

To explore the expression and clinical significance of eukaryotic translation initiation factor 4E(eIF4E) in bone marrow samples of newly diagnosed multiple myeloma (NDMM) patients. Immunohistochemical staining was used to analyze the expression of eIF4E protein in bone marrow biopsy samples from 75 NDMM patients and 25 patients with benign bone marrow disease. Clinical data were collected to analyze the correlation between eIF4E protein expression and clinical features and its prognostic significance in bone marrow samples of NDMM patients. The positive rate of eIF4E protein expression in bone marrow samples of NDMM patients was higher than that in patients with benign bone marrow disease (P<0.001). Positive expression of eIF4E protein was correlated with elevated serum lactate dehydrogenase in MM patients. Univariate and multivariate analysis showed that positive expression of eIF4E protein was significantly associated with shortened overall survival (OS) in NDMM patients, and was an independent risk factor affecting OS in NDMM patients. Positive expression of eIF4E protein is an independent poor prognostic factor for OS in NDMM patients.

Skeletal muscle area predicts the outcomes of non-small-cell lung cancer after trimodality therapy.

Sarcopenia correlates with poor prognosis in various malignancies. However, the prognostic significance of sarcopenia remains to be determined in patients with non-small-cell lung cancer who undergo surgery after receiving neoadjuvant chemoradiotherapy (NACRT). We retrospectively reviewed the patients with stage II/III non-small-cell lung cancer who underwent surgery following NACRT. The paravertebral skeletal muscle area (SMA) (cm2) at the 12th thoracic vertebra level was measured. We calculated the SMA index (SMAI) as SMA/squared height (cm2/m2). Patients were divided into low and high SMAI groups, and the association of SMAI with clinicopathological factors and prognosis was assessed. The patients' [men, 86 (81.1%)] median age was 63 (21-76) years. There were 106 patients including 2 (1.9%), 10 (9.4%), 74 (69.8%), 19 (17.9%) and 1 (0.9%) patients with stage IIA, IIB, IIIA, IIIB and IIIC, respectively. Of the patients, 39 (36.8%) and 67 (63.2%) were classified in the low and the high SMAI groups, respectively. Kaplan-Meier analysis showed that the low group had a significantly shorter overall survival and disease-free survival than the high group. Multivariable analysis identified low SMAI as an independent poor prognostic factor for overall survival. Pre-NACRT SMAI correlates with poor prognosis; therefore, assessing sarcopenia based on pre-NACRT SMAI may help determine optimal treatment strategies and suitable nutritional and exercise interventions.

Outcomes of elderly patients following thoracoscopic esophagectomy for esophageal cancer.

Thoracoscopic esophagectomy (TE) is widely used for esophageal cancer treatment. However, the short- and long-term outcomes of TE in older patients remain unknown. Thus, we investigated those outcomes as well as the effectivity of TE in this patient cohort. A total of 228 consecutive patients who underwent TE for esophageal cancer from 2002 to 2015 were included in the study and categorized into the elderly (≥ 75years) and non-elderly (< 75years) groups. The background was adjusted by propensity score matching. The short- and long-term outcomes were then compared between the two groups. There was no difference in the short-term outcomes between the two groups. The elderly group had significantly lower overall survival (OS) and relapse-free survival (RFS) than the non-elderly group. When pulmonary complications occurred, the OS and RFS were significantly decreased in the elderly group but not in the non-elderly group. Without pulmonary complications, the OS and RFS in the elderly group did not differ from those in the non-elderly group. The multivariate analysis showed that pulmonary complications were independent poor prognostic factors for OS and RFS in the elderly group but not in the non-elderly group. TE is safe and feasible for older patients. However, the OS and RFS of the elderly group were significantly worse than those of the non-elderly group, especially when pulmonary complications occurred. Therefore, perioperative management to prevent pulmonary complications is essential to improve the long-term outcomes of older patients receiving TE.

The impact of postoperative blood glucose levels on complications and prognosis after esophagectomy in patients with esophageal cancer.

This study aimed to characterize postoperative blood glucose fluctuation in patients who underwent esophagectomy for esophageal cancer, and to define its impact on complications and prognosis. The subjects of this retrospective study were 284 patients who underwent esophagectomy at Osaka University Hospital between 2015 and 2017. Data analyzed included clinicopathological background, the immediate postoperative blood glucose level (IPBG), postoperative blood glucose variability (PBGV), insulin dosage, postoperative complications, and prognosis. The median IPBG and PBGV were 170 (64-260) mg/dl and 64.5 (11-217) mg/dl, respectively. Postoperative pneumonia was more common in patients with PBGV > 100mg/dl (P = 0.015). Patients with IPBG < 170mg/dl had significantly worse 5-year overall survival (OS) and 5-year recurrence-free survival (RFS) than those with IPBG > 170mg/dl (54.5% vs. 80.4%, respectively, [P < 0.001] and 44.3% vs. 69.3%, respectively, [P = 0.001]). The 5-year OS rates were 43.5%, 68.3%, 80.6%, and 79.0% for patients with IPBG < 154, 154-170, 170-190, and ≥ 190mg/dl, respectively. The corresponding 5-year RFS rates were 38.1%, 52.4%, 77.0%, and 61.3%, respectively. Multivariate analysis revealed that IPBG < 154mg/dl and pathological stage were independent poor prognostic factors for OS. PBGV was associated with postoperative pneumonia, and low IPBG was an independent poor prognostic factor for patients with esophageal cancer.

The relationship between systemic immune-inflammation indexes and treatment response in locally advanced esophageal cancer

Aim: Systemic immune-inflammation indexes have been reported to be associated with clinical outcomes in several malignancies. Herein, we aimed to evaluate the potential relationship between prognostic nutritional index (PNI), systemic immune-inflammation index (SII), the neutrophil- to- lymphocyte ratio (NLR), the monocyte- to- lymphocyte ratio (MLR), the platelet-to-lymphocyte ratio (PLR) and the treatment response in patients with esophageal cancer who underwent neoadjuvant chemoradiotherapy (CRT).Material and Method: Esophageal cancer (EC) patients who underwent neoadjuvant CRT were retrospectively enrolled in the study. Immune-inflammation indexes were calculated from pretreatment blood counts in samples obtained. The relationships between PNI, SII, NLR, MLR, PLR values, treatment response, and overall survival (OS) rates were examined.Results: The data of 103 patients with EC who were referred to the Radiation Oncology Clinic of Dr Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital were retrospectively analyzed. In the univariate analysis for OS, alcohol consumption, CRT agent, NLR, MLR, PLR, SII and PNI were found as prognostic factors. Also alcohol consumption was found as an independent prognostic factor in multivariate analyzes (HR:5.201, 95% CI:1.9-14.2, p=0.01). Conclusion: In our study, high SII and low PNI values ​​were not found to be independent poor prognostic factors for OS, but lower OS rates were observed in patients with high SII and low PNI values.

Impact of Prior Cancer History on Outcomes of Resected Lung Cancer.

Previous studies concerning the impact of prior cancer on newly diagnosed lung cancer are mainly based on databases and obtained mixed results. Utilizing a large study population, we aimed to reveal this impact. Lung cancer patients from January 2008 to April 2021 were enrolled. The Kaplan-Meier method was used to perform survival analyses. To investigate the impact of prior cancer, a Cox proportional hazards model was conducted. To minimize the influence of the heterogeneity of prior cancer, stratified analyses were carried out. In total, 17,423 lung cancer patients were reviewed, among which we identified 1469 (8.4%) patients with a history of prior cancer. Cox regression analysis revealed that prior cancer was an independent poor prognostic factor on overall survival (HR = 1.430, 95% CI: 1.147-1.784, p = 0.001) but did not affect lung cancer-specific survival (HR = 1.120, 95% CI: 0.876-1.434, p = 0.366). Interestingly, in further stratified analyses, we found that prior cancer history affected overall survival only in pTNM stage 0/I patients (HR = 1.670, 95% CI: 1.247-2.237, p = 0.001), but not in pTNM stage II/III/IV patients (HR = 1.237, 95% CI: 0.877-1.743, p = 0.226). Similarly, prior cancer was an independent poor prognostic factor on overall survival only for pN0 patients. Subsequently, subgroup analyses indicated that the impact of prior cancer varied in pTNM stage 0/I patients according to the type of prior cancer and the interval time. Considering that prior cancer affects overall survival in patients with clinically curable lung cancer, clinicians should pay attention to this effect and improve the management of these patients to achieve a better prognosis.

CMTM6 is highly expressed in lung adenocarcinoma and can be used as a biomarker of a poor diagnosis.

CMTM6 which is chemokine-like factor (CKLF)-like Marvel transmembrane domain containing family member 6 is involved in the occurrence and progression of various tumors. However, the role of CMTM6 is still unclear in lung adenocarcinoma (LUAD). Immunohistochemical, Western blotting and RT‒PCR methods were used to detect the expression of CMTM6 in LUAD. Cox regression and the Kaplan‒Meier method were performed to assess overall survival. Immunogenic features were evaluated according to immune cell infiltrations, immune checkpoints. The sensitivity to chemotherapy agents was estimated using the pRRophetic package. In LUAD, the expression of CMTM6 was obviously upregulated and was significantly associated with T stage (p = 0.008) and lymph node metastasis (p = 0.018). Multivariate Cox regression analysis demonstrated that CMTM6 was a specialty prognostic risk factor. Based on GSEA enrichment analysis, we found that high expression of CMTM6 is associated with multiple immune signaling pathways. The group with high CMTM6 expression showed a positive association with various types of tumor-infiltrating cells. Moreover, a total of 36 chemotherapeutic drugs were significantly correlated with the expression of CMTM6. Among them, two chemotherapeutic drugs had better therapeutic effects in the high CMTM6 expression group, while 34 chemotherapeutic drugs had therapeutic effects in the low CMTM6 expression group. This study confirmed that CMTM6 is highly expressed in LUAD and is a new independent poor prognostic factor. In addition, the high expression of CMTM6 is closely related to the tumor microenvironment and immunotherapy, providing new ideas for the treatment of posterior LUAD.

Dihydropyrimidinase-like 2 can serve as a novel therapeutic target and prognostic biomarker in acute myeloid leukemia.

Identifying therapeutic targets and prognostic biomarkers significantly contributes to individualized treatment of acute myeloid leukemia (AML). Dihydropyrimidinase-like 2 (DPYSL2) expression was decreased in homoharringtonine (HHT)-resistant AML cells, which were established by our group. DPYSL2 plays an important role in axon growth and has oncogene effect in glioblastoma. However, little research has been conducted to investigate the function of DPYSL2 in AML pathogenesis. Auto-docking was used to reveal the targeting relationship between HHT and DPYSL2. Overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) were used to evaluate the prognostic impact of DPYSL2 for AML. ShRNA was used to knockdown the expression of SPATS2L. Apoptosis was assessed by flow cytometry. In vivo growth and survival were assessed using a xenotransplantation mice model. RNA sequencing was performed to elucidate the molecular mechanisms underlying the role of SPATS2L in AML and were confirmed by Western blot. We found DPYSL2 was the target of HHT. Next, we found AML cell lines and patients had higher DPYSL2 expression levels than the normal samples. Further multivariate analysis demonstrated that high DPYSL2 expression was an independent poor prognostic factor for OS, EFS, and RFS in AML. Inhibition of DPYSL2 expression suppressed cell growth, induced apoptosis in AML cell lines, and prolonged the survival of AML xenograft NCG mice. Through RNA-seq analysis from TCGA and our data, the JAK2/STAT3/STAT5-PI3K P85/AKT/GSK3b axis was thought to be the critical pathway in regulating DPYSL2 in AML development. We first time confirmed that DPYSL2 was a target of HHT and played an oncogene role in AML by regulating JAK/STAT signaling pathway. Therefore, DPYSL2 could serve as a novel prognostic marker and therapeutic target for AML treatment.

The prognostic impact of the lymphocyte-to-C-reactive protein ratio in patients with unresectable or recurrent advanced gastric cancer treated with first- and second-line treatment.

The goal of this study was to determine which markers are the most useful as first- and second-line pre-treatment markers in patients with unresectable or recurrent gastric cancer (URGC). This study included 101 URGC patients who were treated with first- and second-line chemotherapy. Several prognostic scores based on nutrition and inflammation were analyzed using a receiver operating characteristic (ROC) analysis to determine the most useful prognostic marker. The lymphocyte-to-C-reactive protein ratio (LCR) had the highest area under the curve for both first- and second-line chemotherapy, according to an ROC analysis. An ROC analysis was used to determine the optimal LCR cut-off for the median survival time before first- and second-line chemotherapy, and patients were divided into high- and low-LCR groups. Patients with a high LCR had a significantly longer survival than those with a low LCR before first- and second-line chemotherapy (p = 0.004, p < 0.001, respectively). A low LCR before both first- and second-line chemotherapy was an independent poor prognostic factor in a multivariate analysis. URGC patients with a low LCR before both first- and second-line chemotherapy had a significantly worse prognosis than those with a high LCR in this study. Nutritional intervention during chemotherapy induction may lead to a better prognosis.

High Red Blood Cell Distribution Width to Platelet Ratio is an Independent Poor Prognostic Factor in Patients with Newly Diagnosed Multiple Myeloma.

The red blood cell distribution width to platelet ratio (RPR) is an inflammatory marker that is a convenient and reliable prognostic indicator for several solid malignancies. However, the correlation between RPR and myeloma prognosis has not been reported. Therefore, this study aims to explore the correlation between RPR level and the prognosis of multiple myeloma (MM) patients. We retrospectively analyzed 145 newly diagnosed patients with MM. The receiver operating characteristic curve (ROC) method was used to determine the RPR cut-off value. In addition, we studied the correlation between pre-treatment RPR levels and clinical characteristics, immunophenotype, cytogenetics, and its impact on the disease prognosis. The optimal cut-off value for RPR was 0.12 and was divided into high RPR and low RPR groups. Patients in the high RPR group are more likely to have anemia, thrombocytopenia, high β2-macroglobulinemia, a high percentage of bone marrow plasma cells, late-stage status by Dury-Salmon (DS) and international staging system (ISS) (p < 0.05). More notably, between the high RPR and low RPR groups, the incidence rates of CD56-positive, D13S319-positive, RB1-positive, and 1q21 amplification were statistically significant (p < 0.05). Additionally, survival analysis revealed that compared with patients in the low RPR group, the median progression-free survival (PFS) and overall survival (OS) of patients in the high RPR group were substantially shortened (p < 0.05). Multivariate analysis confirmed that RPR ≥0.12, D13S319-positive, and 1q21 amplification were independent risk factors for poor PFS and OS. RPR is a practical and effective prognostic marker in newly diagnosed patients with MM, and a high RPR is an independent poor prognostic factor.

Association of Lymphovascular Space Invasion (LVSI) with Histological Tumor Grade and Myometrial Invasion in Endometrial Carcinoma: A Review Study.

Endometrial carcinoma is one of the most frequent gynecological cancers in developed countries. Lymphovascular space invasion (LVSI), histological grade, and myometrial invasion (MMI) are important prognostic factors of endometrial carcinoma. LVSI is considered an independent poor prognostic factor in endometrial carcinoma. Based on the importance of LVSI, this study aimed to discuss the association of LVSI with tumor grade and MMI. A search of PubMed, EMBASE, Web of Science, Scopus, Google Scholar, and Cochrane Library was carried out to collect related studies. Consequently, most studies showed that LVSI is significantly associated with higher histologic grade and deep MMI.

Interleukin-34 cancels anti-tumor immunity by PARP inhibitor.

Breast cancer susceptibility gene 1 (BRCA1)-associated ovarian cancer patients have been treated with A poly (ADP-ribose) polymerase (PARP) inhibitor, extending the progression-free survival; however, they finally acquire therapeutic resistance. Interleukin (IL)-34 has been reported as a poor prognostic factor in several cancers, including ovarian cancer, and it contributes to the therapeutic resistance of chemotherapies. IL-34 may affect the therapeutic effect of PARP inhibitor through the regulation of tumor microenvironment (TME). In this study, The Cancer Genome Atlas (TCGA) data set was used to evaluate the prognosis of IL-34 and human ovarian serous carcinoma. We also used CRISPR-Cas9 genome editing technology in a mouse model to evaluate the efficacy of PARP inhibitor therapy in the presence or absence of IL-34. We found that IL34 was an independent poor prognostic factor in ovarian serous carcinoma, and its high expression significantly shortens overall survival. Furthermore, in BRCA1-associated ovarian cancer, PARP inhibitor therapy contributes to anti-tumor immunity via the XCR1+ DC-CD8+ T cell axis, however, it is canceled by the presence of IL-34. These results suggest that tumor-derived IL-34 benefits tumors by creating an immunosuppressive TME and conferring PARP inhibitor therapeutic resistance. Thus, we showed the pathological effect of IL-34 and the need for it as a therapeutic target in ovarian cancer.