Unfavorable Disease-free Survival Research Articles

Prognostic significance of programmed cell death 1 expression on CD8+T cells in various cancers: a systematic review and meta-analysis.

Increased PD-1 expression on CD8+ T cells is considered as a hallmark for T-cell exhaustion, and is thought to be related to the prognosis of cancer patients. However, discrepant results have made it difficult to apply PD-1+CD8+T cells and tumor prognosis to clinical practice. Therefore, we conducted a meta-analysis to evaluate its prognostic value in human cancers. PRISMA reporting guidelines were strictly followed for conducting the current meta-analysis. The PubMed, Web of Science, Embase databases were searched from inception to November 2024. The pooled Hazard Ratio (HR) along with 95% confidence intervals (CIs) of each article were combined for the associations of PD-1+CD8+ T cells with overall survival (OS), progression- free survival (PFS) and disease-free survival(DFS). Subgroup analyses were performed for area, specimen type, cancer type, treatment, detected method and cancer stage. A total of 20 studies (23 cohorts, 3086 cancer patients) were included in our study. The expression PD-1+CD8+ T cells in cancer patients tended to predict poor overall survival (OS) (HR: 1.379, 95%CI: 1.084-1.753, p= 0.009), and unfavorable disease-free survival(DFS) (HR: 1.468, 95%CI: 0.931-2.316, p=0.099), though it did not reach statistical significance. Begg's and Egger's test demonstrated that no obvious publication bias was exist. High PD-1 expression on CD8+ T cells is associated with worse survival outcomes, which can be potentially used as a prognostic marker of malignant tumor.

Low Expression of FAM96B is Associated with Poor Prognosis in Hepatocellular Carcinoma.

Recently, studies on FAM96B functions mainly focused on its role in maintaining the normal physiological function of cells. However, the clinical implications of FAM96B in hepatocellular carcinoma (HCC) are still unclear. FAM96B mRNA expression was detected in human HCC tissues and the matched nontumorous tissues by quantitative real-time reverse transcription (qRT-PCR) and then validated in The Cancer Genome Atlas (TCGA) database. Immunohistochemistry assay (IHC) was performed on all 137 cases of HCC samples to examine the protein level of FAM96B. Subsequently, the associations between FAM96B expression and clinicopathological parameters and prognosis were further analyzed. The mRNA level of FAM96B was found to be significantly lower in HCC tissues compared to non-tumorous tissues, as observed in both the local hospital and TCGA database.Immunohistochemistry assay analysis revealed a decrease in FAM96B expression in 78 out of 137 cases, which was significantly associated with larger tumor size, higher Barcelona clinic liver cancer or Child stage, and early distant metastasis. Patients with low FAM96B levels tended to have an unfavorable disease-free and overall survival. Moreover, FAM96B was identified as an independent predictor of patient prognosis in both univariate and multivariate survival analyses. Mechanistically, FAM96B was found to inhibit cancer progression by inducing apoptosis in liver cancer cells and inhibiting their growth. Our findings provide the first evidence suggesting the involvement of FAM96B in the progression of HCC. Additionally, FAM96B could potentially serve as a marker for tumor recurrence and prognosis in HCC patients.

Computed tomography radiomics reveals prognostic value of immunophenotyping in laryngeal squamous cell carcinoma: a comparison of whole tumor- versus habitats-based approaches

BackgroundTo compare the performance of whole tumor and habitats-based computed tomography (CT) radiomics for predicting immunophenotyping in laryngeal squamous cell carcinomas (LSCC) and further evaluate the stratified effect of the radiomics model on disease-free survival (DFS) and overall survival (OS) of LSCC patients.MethodsIn all, 106 LSCC patients (40 with inflamed and 66 with non-inflamed immunophenotyping) were randomly assigned into a training (n = 53) and testing (n = 53) cohort. Briefly, 750 radiomics features from contrast-enhanced CT images were respectively extracted from the whole tumor and two Otsu method-derived subregions. Intraclass correlation coefficients (ICCs) were calculated to evaluate the reproducibility. The radiomics models for predicting immunophenotyping were respectively created using K-nearest neighbors (KNN), logistic regression (LR), and Naive bayes (NB) classifiers. The performance of models in the testing cohort were compared using area under the curve (AUC). The prognostic value of the optimal model was determined by survival analysis.ResultsThe radiomics features derived from whole tumor showed better reproducibility than those derived from habitats. The best model for the whole tumor (LR classifier) showed superior performance than that for the habitats (KNN classifier) in the testing cohort, but there were no significant differences (AUC: 0.741 vs. 0.611, p = 0.112). Multivariable Cox regression analysis showed that the immunophenotyping predicted by the optimal model was an independent risk factor of unfavorable DFS (p = 0.009) and OS (p = 0.008) in LSCC patients.ConclusionsWhole tumor-based CT radiomics could serve as a potential predictive biomarker of immunophenotyping and outcome prediction in LSCC patients.

Keratin-15 high expression links with lymph node metastasis and poor survival prognosis in epithelial ovarian cancer patients

BackgroundKeratin-15 (KRT15) involves in the progression and owns prognostic values in several solid cancers, whose clinical role in epithelial ovarian cancer (EOC) is rarely reported. This study aimed to identify the association of KRT15 expression with tumor features and survival of surgical EOC patients.MethodsFormalin-fixed paraffin-embedded tumor tissues of 140 EOC patients who underwent tumor resection were retrieved for KRT15 determination using immunohistochemistry (IHC) assay.ResultsThe median (interquartile range) KRT15 IHC score was 0.0 (0.0–1.0), ranging from 0.0 to 12.0. Among all, 36.4% of patients had positive KRT15 expression (IHC score > 0) and 15.0% of patients had high KRT15 expression (IHC score > 3). KRT15 was positively related to lymph node metastasis incidence (P = 0.027), and showed a tendency to correlate to FIGO stage but without statistical significance (P = 0.052), while it was not correlated with age, other tumor features, and tumor markers. Positive KRT15 expression was linked with poor disease-free survival (DFS) (P = 0.009) and overall survival (OS) (P = 0.032). Notably, high KRT15 expression showed an even stronger relationship with worse DFS (P = 0.001) and OS (P < 0.001). After adjustment of multivariable Cox’s regression, high KRT15 expression was independently correlated with unfavorable DFS (hazard ratio (HR): 2.241, P = 0.007).ConclusionEven though KRT15 is insufficiently expressed in EOC tissues generally, its positive expression or high expression can predict the lymph node metastasis and poor survival prognosis in EOC patients who undergo tumor resection.

Association between the antibiotics use and recurrence in patients with resected colorectal cancer: EVADER-1, a nation-wide pharmaco-epidemiologic study

BackgroundThe impact of antibiotics (ATBs) on the risk of colorectal cancer (CRC) recurrence after curative resection remains unknown. MethodsUsing the French nation-wide database of cancer patients, all newly diagnosed non-metastatic CRC patients resected between 01/2012 and 12/2014 were included. The perioperative ATB intake (from 6 months before surgery until 1 year after) was classified according to the class, the period of use (pre- vs post-resection), the disease stage (localized and locally advanced), and the primary tumor location (colon and rectum/junction). The primary endpoint was the 3-year disease-free survival (DFS). The impact of ATB was assessed using time-dependent multivariate Cox models. ResultsA total of 35,496 CRC patients were included. Seventy-nine percent of patients had at least one ATB intake. Outpatient ATB intake after surgery was associated with unfavorable 3-year DFS. The ATBs associated with decreased 3-year DFS were cephalosporins, streptogramins, quinolones, penicillin A with beta-lactamase inhibitors, and antifungals with differential effects according to the primary tumor location and disease stage. ConclusionThese findings suggest that ATBs modulate the risk of recurrence after early CRC resection with a differential impact of the ATB classes depending on disease stage and tumor site.

Comprehensive Analysis of Immune Responses to Neoadjuvant Immunotherapy in Resectable Non-small Cell Lung Cancer.

Neoadjuvant immunotherapy using immune checkpoint inhibitors (ICIs) has revolutionized the treatment of early stage non-small cell lung cancer (NSCLC). However, little is known about which patients are likely to benefit most from neoadjuvant immunotherapy. In this study, we performed a multiplatform analysis on samples from resectable NSCLC treated with neoadjuvant immunotherapy to explore molecular characteristics related to immune responses. A total of 17 patients with resectable stage IB-IIIA NSCLC treated with neoadjuvant immunotherapy were included. A multiplex cytokine assay, bulk TCR sequencing in peripheral blood, and multiplexed immunohistochemistry were performed. Low levels of stromal cell-derived factor (SDF)-1alpha at baseline were associated with unfavorable disease-free survival (DFS). Patients with major pathologic response (MPR) showed a decrease in HGF after one cycle of neoadjuvant immunotherapy. An increase in IDO and IP-10 was observed in patients who developed immune-related adverse events (irAEs) after neoadjuvant immunotherapy. There were no correlations between irAEs and MPR or DFS. The MPR group presented a significant decrease in white blood cells and neutrophil count after neoadjuvant immunotherapy. The high peripheral baseline TCR convergence was correlated with MPR and favorable DFS in lung squamous cell carcinoma (LUSC) receiving neoadjuvant immunotherapy. Neoadjuvant immunotherapy led to a significant increase in CD4+, CD8+, and CD8+CD39+ T-cell infiltration in tumor areas. This study suggests the potential roles of cytokines and TCR convergence for predicting ICIs response in resectable NSCLC and LUSC. CD8+CD39+T cells and CD4+ T cells could be involved in the action of neoadjuvant immunotherapy.

Prognostic and clinicopathological significance of fibrinogen-to-albumin ratio (FAR) in patients with breast cancer: a meta-analysis

BackgroundThe fibrinogen-to-albumin ratio (FAR) has been extensively studied for its role in predicting the prognosis of breast cancer (BC) patients; however, existing findings are conflicting. Therefore, this meta-analysis was conducted to identify the significance of FAR in predicting BC prognosis.MethodsWe searched PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure databases until May 25, 2024. The value of FAR for predicting overall survival (OS) and disease-free survival (DFS) in BC was examined by calculating the combined hazard ratios (HRs) and 95% confidence intervals (CIs). Correlations between FAR and clinicopathological factors were analyzed using combined odds ratios (ORs) and 95% CIs.ResultsEight studies involving 4094 patients were included in this work. As shown by our combined data, increased FAR significantly predicted poor OS (HR = 2.84, 95% CI = 1.83–4.39, p < 0.001) and poor DFS (HR = 2.43, 95% CI = 1.66–3.58, p < 0.001) of BC. Moreover, the combined data showed that increased FAR was significantly correlated with age ≥ 50 years (OR = 2.04, 95% CI = 1.37–3.04, p < 0.001), stage III cancer (OR = 1.53, 95% CI = 1.04–2.27, p = 0.033), and the presence of lymph node metastases (OR = 1.33, 95% CI = 1.11–1.61, p = 0.002). Nonetheless, FAR was not significantly associated with tumor size, ER/PR/HER-2 status, or lymphovascular invasion in patients with BC.ConclusionIn this meta-analysis, higher FAR was significantly associated with unfavorable OS and DFS in patients with BC and significantly correlated with several features predictive of cancer development in BC.

Prognostic importance of modified geriatric nutritional risk index in oral cavity squamous cell carcinoma

We probed the associations of preoperative modified geriatric nutritional risk index (mGNRI) values with prognosis in patients receiving surgery for oral cavity squamous cell carcinoma (OCSCC). This retrospective study analyzed the clinical data of 333 patients with OCSCC and undergoing surgery between 2008 and 2017. The preoperative mGNRI was calculated using the following formula: (14.89/C-reactive protein level) + 41.7 × (actual body weight/ideal body weight). We executed receiver operating characteristic curve analyses to derive the optimal mGNRI cutoff and employed Kaplan–Meier survival curves and Cox proportional hazard model to probe the associations of the mGNRI with overall survival (OS) and disease-free survival (DFS). The optimal mGNRI cutoff was derived to be 73.3. We noted the 5-year OS and DFS rates to be significantly higher in the high-mGNRI group than in the low-mGNRI group (both p < 0.001). A preoperative mGNRI below 73.3 was independently associated with unfavorable DFS and OS. A mGNRI-based nomogram was constructed to provide accurate OS predictions (concordance index, 0.781). Hence, preoperative mGNRI is a valuable and cost-effective prognostic biomarker in patients with OCSCC. Our nomogram facilitates the practical use of mGNRI and offers individualized predictions of OS.

Prognostic impact of CD68+ tumor-associated macrophages in hepatocellular carcinoma: A meta-analysis.

Evidence from clinical research suggests that the tumor-associated macrophages (TAMs) were associated with prognosis in hepatocellular carcinoma (HCC). The aim of the present meta-analysis was to conduct a qualitative analysis to explore the prognostic value of CD68 + TAMs in HCC. This study conducted a systematic search in Pubmed, Embase, the Cochrane Library and China National Knowledge Internet from inception of the databases to November 2023. The hazard ratio (HR) and 95% confidence interval (CI) were calculated employing fixed-effect or random-effect models depending on the heterogeneity of the included trials. The Newcastle-Ottawa Scale was used to evaluate the risk of prejudice. We analyzed 4362 HCC patients. The present research indicated that the expression levels Of CD68 + TAMs were significantly associated with overall survival (OS) (HR = 1.55, 95% CI: 1.30-1.84) and disease-free survival (DFS) (HR = 1.44, 95% CI: 1.17-1.78). Subgroup analysis based on cutoff values showed that the "Median" subgroup showed a pooled HR of 1.66 with a 95% CI ranging from 1.32 to 2.08, which was slightly higher than the "Others" subgroup that exhibited a pooled HR of 1.40 and a 95% CI of 1.07 to 1.84. The "PT" subgroup had the highest pooled HR of 1.68 (95% CI: 1.19-2.37), indicating a worse OS compared to the "IT" (pooled HR: 1.50, 95% CI: 1.13-2.01) and "Mix" (pooled HR: 1.52, 95% CI: 1.03-2.26) subgroups. Moreover, in the sample size-based analysis, studies with more than 100 samples (>100) exhibited a higher pooled HR of 1.57 (95% CI: 1.28 to 1.93) compared to studies with fewer than 100 samples (<100), which had a pooled HR of 1.45 (95% CI: 1.00-2.10). The analysis suggests that CD68 + TAMs were significantly associated with unfavorable OS and DFS in HCC patients, and may be served as a promising prognostic biomarker in HCC. However, more large-scale trials are needed to study the clinical value of TAMs in HCC.

Molecular and immune characterization of Chinese early-stage non-squamous non-small cell lung cancer: a multi-omics cohort study.

Albeit considered with superior survival, around 30% of the early-stage non-squamous non-small cell lung cancer (Ns-NSCLC) patients relapse within 5 years, suggesting unique biology. However, the biological characteristics of early-stage Ns-NSCLC, especially in the Chinese population, are still unclear. Multi-omics interrogation of early-stage Ns-NSCLC (stage I-III), paired blood samples and normal lung tissues (n=76) by whole-exome sequencing (WES), RNA sequencing, and T-cell receptor (TCR) sequencing were conducted. An average of 128 exonic mutations were identified, and the most frequently mutant gene was EGFR (55%), followed by TP53 (37%) and TTN (26%). Mutations in MUC17, ABCA2, PDE4DIP, and MYO18B predicted significantly unfavorable disease-free survival (DFS). Moreover, cytobands amplifications in 8q24.3, 14q13.1, 14q11.2, and deletion in 3p21.1 were highlighted in recurrent cases. Higher incidence of human leukocyte antigen loss of heterozygosity (HLA-LOH), higher tumor mutational burden (TMB) and tumor neoantigen burden (TNB) were identified in ever-smokers than never-smokers. HLA-LOH also correlated with higher TMB, TNB, intratumoral heterogeneity (ITH), and whole chromosomal instability (wCIN) scores. Interestingly, higher ITH was an independent predictor of better DFS in early-stage Ns-NSCLC. Up-regulation of immune-related genes, including CRABP2, ULBP2, IL31RA, and IL1A, independently portended a dismal prognosis. Enhanced TCR diversity of peripheral blood mononuclear cells (PBMCs) predicted better prognosis, indicative of a noninvasive method for relapse surveillance. Eventually, seven machine-learning (ML) algorithms were employed to evaluate the predictive accuracy of clinical, genomic, transcriptomic, and TCR repertoire data on DFS, showing that clinical and RNA features combination in the random forest (RF) algorithm, with area under the curve (AUC) of 97.5% and 83.3% in the training and testing cohort, respectively, significantly outperformed other methods. This study comprehensively profiled the genomic, transcriptomic, and TCR repertoire spectrums of Chinese early-stage Ns-NSCLC, shedding light on biological underpinnings and candidate biomarkers for prognosis development.

Minimal Extrathyroid Extension (mETE) as the Only Risk Factor in Patients with Papillary Thyroid Carcinoma (PC): Its Clinical Impact on Recurrence and Outcome during Long-Term Follow-Up.

Minimal extrathyroid extension (mETE) effect on papillary thyroid carcinoma (PC) prognosis is still debated even more so now that this factor has been removed in the 8th AJCC Edition, supporting the hypothesis that mETE is not associated with aggressive tumors. We retrospectively enrolled 91 PC patients (Group 1) submitted to total thyroidectomy and radioiodine ablation. At the time of the primary tumor surgery, mETE was ascertained in all patients with no other risk factors, such as multifocality, vascular invasion, neck and distant metastases, and aggressive histological variants. As controls, 205 consecutive matched PC patients (Group 2) without mETE and the aforementioned risk factors were enrolled. During the follow-up (average 8 years), 16/91 (17.58%) Group 1 patients and 15/205 (7.32%) Group 2 patients developed metastases (p = 0.0078). Cox regression analysis showed an increased risk of metastases in patients with mETE (HR: 2.58 (95% CI 1.28-5.22) p = 0.008). Disease-free survival (DFS) was significantly lower in patients with mETE than in controls (p = 0.0059). The present study seems to demonstrate that mETE can be associated with an aggressive PC and can be considered, even alone without other risk factors, an independent factor of unfavorable DFS. Thus, by excluding mETE in the 8th AJCC Edition, patient care and management could be compromised.

PYCR1, BANF1, and STARD8 Expression in Gastric Carcinoma: A Clinicopathologic, Prognostic, and Immunohistochemical Study.

It will be important to understand the molecular pathways of gastric cancer (GC) occurrence and progression, thus detecting predictive and prognostic biomarkers of GC. Pyrroline-5-carboxylate reductase 1 (PYCR1) was upregulated in many cancers, suggesting its possible roles in carcinogenesis and tumor metastases. Barrier-of-autointegration factor 1 (BANF1) is a protein family that plays essential roles in maintaining the integrity of an intact cellular genome. Rho-GTPs are molecular switches that control many signal transduction pathways in normal cells, including 3 subgroups from 1 to 3 (DLC1-3). DLC-3, known as StAR-related lipid transfer domain protein 8 (STARD8), and its role in cancers were not sufficiently studied. The study aimed to investigate the significance of PYCR1, BANF1, and STARD8 protein expression in GC tissues and normal gastric mucosa retrieved from patients with GC to detect prognostic roles of expression. Specimens were collected from 100 patients with gastric carcinoma. After the application of the inclusion criteria of the study, we prepared 100 paraffin blocks from samples of the 100 included patients; each block included samples from gastric carcinoma and adjacent non-neoplastic gastric mucosa. We assessed the expression of PYCR1, BANF1, and STARD8 using immunohistochemistry in all studied samples. We followed patients for the detection of disease progression and survival rates. We correlate PYCR1, BANF1, and STARD8 expression with clinical, pathologic, and prognostic parameters. Overexpression of PYCR1 and BANF1 and decreased expression of STARD8 was found in gastric carcinoma tissues than adjacent non-neoplastic gastric mucosa ( P <0.001), and was positively associated with high grade ( P =0.006), depth of tumor invasion, presence of lymph nodes metastases and advanced stage ( P =0.001), high incidence of GC progression, recurrence, unfavorable disease-free survival ( P =0.003) and unfavorable overall survival rates ( P <0.001). Thus, it was revealed that; in univariate and multivariate analyses, levels of PYCR1, BANF1, and STARD8 are associated with the overall survival rate of GC patients. We showed that overexpression of PYCR1 and BANF1 and decreased expression of STARD8 in GC tissues was associated with poor prognosis and GC progression.

A Comparative Analysis of Effect of HIV Infection on Outcomes of Cervical Cancer Treated with Radiotherapy

There is paucity of data on management of human immunodeficiency virus (HIV) positive cervical cancer and its clinical outcomes in Indian women. The primary objective of this study was to compare disease free survival (DFS) and overall survival (OS) between HIV-positive and HIV-negative patients receiving radiotherapy (RT) for cervical cancer. The secondary endpoints were toxicity and various factors affecting DFS and OS. Patients diagnosed with cervical cancer on histopathology and treated with RT with or without concomitant chemotherapy (CT) at an institution between 2015 and 2020 were included in this retrospective analysis. On the basis of HIV serology test, 70 patients were included in each arm, Arm A had HIV-negative patients and Arm B had HIV-positive patients. In both the arms, external beam radiotherapy (EBRT) in adjuvant or radical setting was given with a total dose of 46-50 Gy to whole pelvis and iliac nodes; 2 Gy/fraction daily as 5 fractions/week by conventional four-field box technique or conformal 3-dimensional radiotherapy (3DCRT) or Intensity modulated radiotherapy (IMRT). Concurrent cisplatin was administered as weekly 40mg/m2 to patients with ECOG< = 2, creatinine clearance >40mL/min in radical and adjuvant patients as indicated. CD4 counts ≥200 cells/mm3 was a prerequisite for concurrent cisplatin in Arm B. Intracavitary or interstitial brachytherapy was delivered as indicated. Statistical analysis was done using statistical software. Kaplan-Meier method used for all survival analysis. Log rank test was used to calculate statistical significance for various prognostic factors followed by Cox regression test for multivariate analysis. Median age was 46.5 years (range: 30-76). In Arm A, 62 patients (88.57%) and 5 patients (7.14%) received radical and adjuvant RT. In Arm B 61 patients (87.14%) and 2 patients (2.85%) were given radical and adjuvant RT. 66 patients (94.28%) in Arm A and 52 patients (74.28%) in Arm B received concurrent cisplatin. At a median follow up of 33.8 months (range: 1.2 to 85.4), 2-year DFS was 88.9% for Arm-A and 86.5% for Arm-B (p = 0.134) and 2-year OS was 91.4% and 82.9% for Arm-A and Arm-B (p = 0.001), respectively. Grade III/IV skin toxicity was seen in and 4 patients (5.71%) in Arm A and 12 patients (17.14%) in Arm B (p = 0.34). Grade III/IV gastrointestinal toxicity was seen in 2(2.85%) patients and 4(5.7%) patients in Arm A and Arm B respectively (p = 0.40). 14(20%) patients in Arm A and 27(38.5%) patients in Arm B had Grade III/IV hematologic toxicity (p = 0.016). On multivariate analysis, anemia (Hb≤12 gm/dl) and OTT ≥56 days were associated with unfavorable DFS (p = 0.03 and p = 0.001) and OS (p = 0.04 and p = 0.01) in Arm B. In view of comparable DFS outcomes in both the arms, HIV-positive cervical cancer patients can be managed with the standard treatment protocol as HIV-negative patients. HIV-positive patients are more likely to experience poorer DFS and OS. However, results need to be validated on prospective study.

Subcellular Expression Patterns of FKBP Prolyl Isomerase 10 (FKBP10) in Colorectal Cancer and Its Clinical Significance.

FKBP10, a member of the FK506-binding protein (FKBP) family, has been implicated in cancer development, although its prognostic function remains controversial. In this study, we analyzed the expression of FKBP10 in tumor tissues using online databases (TCGA) as well as our CRC cohort, and investigated the relationship between its subcellular expression pattern and patient outcomes. Cox regression analysis was used to determine the associations between different subcellular expression patterns of FKBP10 and clinical features of patients. We also discussed the expression level of FKBP10 based on different subcellular expression patterns. Our results showed that FKBP10 was significantly elevated in CRC tissues and exhibited three different subcellular expression patterns which were defined as 'FKBP10-C' (concentrated), 'FKBP10-T' (transitional) and 'FKBP10-D' (dispersive). The FKBP10-D expression pattern was only found in tumor tissues and was associated with unfavorable disease-free survival in CRC patients. High expression levels of FKBP10-C predicted an unfavorable prognosis of recurrence of CRC, while FKBP10-D did not. Our findings suggest that the subcellular expression patterns and expression level of FKBP10 play crucial prognostic roles in CRC, which revealed that FKBP10 may be a viable prognostic and therapeutic target for the diagnosis and treatment of CRC.

Nuclear Factor Erythroid 2-Related Factor 2/Kelch-Like ECH-Associated Protein 1 as a Predictor of Prognosis and Radiotherapy Resistance in Patients With Locally Advanced Rectal Cancer: A Prospective Analysis.

The nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) signaling pathway is involved in the regulation of cellular responses to oxidative stress. Nrf2 acts as a cell protector from inflammation, cellular damage, and tumorigenesis, whereas Keap1 is a negative regulator of Nrf2. Dysregulation of the Nrf2/Keap1 pathway results in tumorigenesis and the active metabolism of tumor cells, leading to high resistance to radiotherapy. This study aimed to evaluate the predictive role of Nrf2 and Keap1 in the radiosensitivity and prognosis of locally advanced rectal cancer (LARC). In total, 90 patients with LARC underwent surgery after preoperative chemoradiotherapy (CRT). Endoscopic biopsies from the tumors were obtained before radiation, and the Nrf2 and Keap1 expressions were assessed by immunohistochemistry. The response to therapy was evaluated after surgery following CRT according to the pathologic tumor regression grade. The disease-free survival (DFS) and overall survival rates were also documented. The association between the Nrf2 and Keap1 immunoreactivity and the clinicopathological parameters was analyzed. The overexpression of the nuclear Nrf2 before CRT showed a significant correlation with better DFS. The cytoplasmic Nrf2 expression was associated with more residual tumors after radiotherapy and a more unfavorable DFS, indicating lower radiosensitivity. CRT is an important issue in LARC and is a major aspect of treatment. Thus, the Nrf2/Keap1 expression may be a potential predictor of preoperative therapeutic resistance. The Nrf2-Keap1 modulators that interact with each other may also be effectively applicable to CRT effect in LARC.

Prognostic significance of N6-methyladenosine-modified related chemotransferase METTL3 in gastric carcinoma: Evidence from meta-analysis.

N6-methyladenosine (m6A) methylation is known as the research hotspot for tumor epimodification, and its associated methyltransferase-like3 (METTL3) is significantly differentially expressed in gastric carcinoma, but its clinical value has not been summarized. This meta-analysis aimed to evaluate the prognostic significance of METTL3 in gastric carcinoma. Databases, including PubMed, EMBASE (Ovid platform), Science Direct, Scopus, MEDLINE, Google Scholar, Web of Science, and Cochrane Library, were used to identify relevant eligible studies. The endpoints included overall survival, progression-free survival, recurrence-free survival, post-progression survival, and disease-free survival. Hazard ratios (HR) with 95% confidence intervals (CI) were used to correlate METTL3 expression with prognosis. Subgroup and sensitivity analyses were performed. Seven eligible studies involving 3034 gastric carcinoma patients were recruited for this meta-analysis. The analysis showed that high METTL3 expression was associated with significantly poorer overall survival (HR = 2.37, 95% CI 1.66-3.39, P < 0.01) and unfavorable disease-free survival (HR = 2.58, 95% CI 1.97-3.38, P < 0.01), as did unfavorable progression-free survival (HR = 1.48, 95% CI 1.19-1.84, P < 0.01)/recurrence-free survival (HR = 2.62, 95% CI 1.93-5.62, P < 0.01)/post-progression survival (HR = 1.53, 95% CI 1.22-1.91, P < 0.01). Subgroup analysis found that high METTL3 expression was associated with worse overall survival in patients with Chinese (HR = 2.21, 95% CI 1.48-3.29, P < 0.01), in studies with sample source from formalin-fixed, paraffin-embedded tissues (HR = 2.66, 95% CI 1.79-3.94, P < 0.01), and the reported directly from articles group (HR = 2.42, 95% CI 1.66-3.53, P < 0.01). The subgroup analysis that was performed based on sample size, detected method, and follow-up showed the same results. High expression of METTL3 predicts poor prognosis in gastric carcinoma, indicating promise for METTL3 as a prognostic biomarker.Systematic review registration: https://www.crd.york.ac.uk/prospero, ID = CRD42023408519.

A pan-cancer analysis of high mobility group box 1 and its role in human tumorigenesis

Understanding the specific and co-driving mechanisms of carcinogenesis in human tumors is indispensable for cancer research and can guide the development of effective treatment methods for tumors. High mobility group box 1 (HMGB1) participates in a variety of physiological processes of the body and has an inseparable relationship with tumors. In this study, The Cancer Genome Atlas, Gene Expression Omnibus database, Human Protein Atlas, and bioinformatic tools were used to conduct pan-cancer analysis of HMGB1 in various cancers so as to elucidate its role in human tumorigenesis. We analyzed and evaluated the expression of HMGB1 in tumors, and discovered that overexpression of HMGB1 usually indicated poor overall survival of adrenocortical carcinoma (P &lt; 0.01) and lung adenocarcinoma (LUAD) (P &lt; 0.05). High HMGB1 expression is also associated with unfavorable disease-free survival for patients with adrenocortical carcinoma (P &lt; 0.001), cervical squamous cell carcinoma and endocervical adenocarcinoma (P &lt; 0.01), head and neck squamous cell carcinoma (P &lt; 0.05), LUAD (P &lt; 0.05), and sarcoma (P &lt; 0.05). The potential mechanism of HMGB1-mediated tumorigenesis is also discussed. In conclusion, our pan-cancer analysis offers a comprehensive description of the carcinogenic roles of HMGB1 in a variety of human cancers.

Polo-like kinase (PLK) 5, a new member of the PLK family, serves as a biomarker to indicate anabatic tumor burden and poor prognosis for resectable non-small cell lung cancer.

A review argues that polo-like kinase 5 (PLK5) may be linked to unfavorable prognosis in non-small cell lung cancer (NSCLC) patients, which contradicts the discoveries from The Human Protein Atlas database (derived from TCGA analysis). This study intended to comprehensively confirm the association of PLK5 with clinical characteristics and prognosis in NSCLC patients. This two-center, retrospective, cohort study enrolled 210 NSCLC patients receiving surgical resection. PLK5 protein and mRNA were detected by immunohistochemistry and RT-qPCR in tumor and nontumor tissues. Moreover, RNA FPKM data for 994 lung cancer patients were obtained from The Human Protein Atlas database. PLK5 protein was decreased in tumor tissue compared to nontumor tissue (P < 0.001). Additionally, decreased PLK5 protein was linked with increased pathological grade (P = 0.002), lymph node metastasis presence (P = 0.001), elevated tumor-node-metastasis (TNM) stage (P = 0.003), and abnormal cancer antigen 125 (CA125) (P = 0.002). Meanwhile, low PLK5 protein was correlated with shortened disease-free survival (DFS) (P = 0.007) and overall survival (OS) (P = 0.038); further multivariable Cox regression analysis revealed that low PLK5 protein independently predicted unfavorable DFS (hazard ratio = 0.573, P = 0.022). PLK5 mRNA was reduced in tumor tissue compared with nontumor tissue (P < 0.001); its decline was linked with enhanced pathological grade (P = 0.034), climbed TNM stage (P = 0.032), and abnormal CA125 (P = 0.002). Furthermore, low PLK5 mRNA was correlated with unfavorable DFS (P = 0.046). The Human Protein Atlas database also disclosed the link between low PLK5 mRNA and worse OS (P = 0.046). A PLK5 decrement reflects anabatic tumor burden and poor prognosis in NSCLC patients.

Tumor characteristics, therapy, and prognosis in young breast cancer patients ≤ 35years.

Young breast cancer patients aged 35years and younger are a small group of women who tend to present at high-risk form of the disease. More analysis of the data on tumor characteristics, treatment, and survival is necessary to help improving treatment and outcome. In this retrospective study, we compared the clinical and tumor characteristics, the treatments, and the survival of 257 women aged ≤ 35years, with 6566 women aged 50-69years. We used a registry-based data of patients with invasive, non-metastatic breast cancer diagnosed between 2000 and 2015. Young women showed lower rate of hormone receptor (HR) positivity. Their tumors were more often HER2-positive, which showed lower rate of differentiation and higher rate of Ki-67 expression compared to their older counterparts. Women aged 35years and younger were more likely to undergo neoadjuvant therapy and mastectomy. Endocrine therapy was underrepresented in young patients. 5-Year disease-free survival (DFS) was significantly lower in the younger patient group (81.7% vs. 91.3%, p < 0.001), while 5-year overall survival (OS) was not impaired (91.4% vs. 91.1%, p = 0.847). The unfavorable disease-free survival in the group of younger patients might be explained by their unfavorable tumor characteristics. The surgical treatment appears to be more aggressive in young breast cancer patients and is more frequently combined with chemotherapy and immunotherapy, either in a neoadjuvant or in an adjuvant setting.

Glucose metabolic heterogeneity correlates with pathological features and improves survival stratification of resectable lung adenocarcinoma.

We investigated whether glycolytic heterogeneity correlated with histopathology, and further stratified the survival outcomes pertaining to resectable lung adenocarcinoma. We retrospectively analyzed the 18F-fluorodeoxyglucose positron emission tomography-derived entropy and histopathology from 128 patients who had undergone curative surgery for lung adenocarcinoma. Disease-free survival (DFS) and overall survival (OS) were analyzed using univariate and multivariate Cox regression models. Independent predictors were used to construct survival prediction models. Entropy significantly correlated with histopathology, including tumor grades, lympho-vascular invasion, and visceral pleural invasion. Furthermore, entropy was an independent predictor of unfavorable DFS (p = 0.031) and OS (p = 0.004), while pathological nodal metastasis independently predicted DFS (p = 0.009). Our entropy-based models outperformed the traditional staging system (c-index = 0.694 versus 0.636, p = 0.010 for DFS; c-index = 0.704 versus 0.630, p = 0.233 for OS). The models provided further survival stratification in subgroups comprising different tumor grades (DFS: HR = 2.065, 1.315, and 1.408 for grade 1-3, p = 0.004, 0.001, and 0.039, respectively; OS: HR = 25.557, 6.484, and 2.570, for grade 1-3, p = 0.006, < 0.001, and = 0.224, respectively). The glycolytic heterogeneity portrayed by entropy is associated with aggressive histopathological characteristics. The proposed entropy-based models may provide more sophisticated survival stratification in addition to histopathology and may enable personalized treatment strategies for resectable lung cancer.