Survival In Laryngeal Carcinoma Patients Research Articles

Diagnostic and prognostic nomograms for laryngeal carcinoma patients with lung metastasis: a SEER-based study.

To establish two nomograms to quantify the risk of lung metastasis (LM) in laryngeal carcinoma (LC) and predict the overall survival of LC patients with LM. Totally 9515 LC patients diagnosed histologically from 2000 to 2019 were collected from the Surveillance, Epidemiology, and End Results database. The independent diagnostic factors for LM in LC patients and prognostic factors for LC patients with LM were identified by logistic and Cox regression analysis, respectively. Nomograms were established based on regression coefficients and evaluated by receiver operating characteristic curve, calibration curves, and decision curve analysis. Patients with supraglottis, higher pathological grade, higher N stage, and distant metastasis (bone, brain, or liver) were more likely to have LM (P < 0.05). Chemotherapy, surgery and radiotherapy were independent factors of the overall survival of LC patients with LM (P < 0.05). The area under curve of diagnostic nomogram were 0.834 and 0.816 in the training and validation cohort respectively. For the prognostic nomogram, the area under curves of 1-, 2-, and 3-years were 0.735, 0.734, and 0.709 in the training cohort and 0.705, 0.803, and 0.809 in the validation cohort. The calibration curves and decision curve analysis indicated good performance of the nomograms. Distant metastasis (bone, brain, or liver) and N stage should be considered for prediction of LM in LC patients. Chemotherapy is the most significant influencing prognostic factor improving the survival of LC patients with LM. Two nomograms may benefit for providing better precautionary measures and treatment decision.

UBR5 regulates proliferation and radiosensitivity in human laryngeal carcinoma via the p38/MAPK signaling pathway.

Laryngeal carcinoma (LCC) is a common malignant tumor with low radiosensitivity and generally poor response rates. The ubiquitin protein ligase E3 component n-recognin 5 (UBR5) has prognostic implications in several neoplasms; however, its role in LCC and radiotherapy sensitivity remains unknown. Immunohistochemistry and bioinformatics analyses were performed to measure UBR5 protein and mRNA expression in LCC and adjacent non-tumor tissues. The gene and protein expression of UBR5 in LCC and HuLa-PC cell lines were measured using quantitative PCR and western blot analyses. Following transfection with small interfering RNA or UBR5 overexpression plasmid in LCC cells, the proliferation, cell cycle distribution, invasion, migration and radiosensitivity of LCC cells were analyzed. UBR5-related lncRNA, targeted miRNA and protein-protein interaction networks were analyzed using bioinformatics. Finally, the expression of the p38/mitogen-activated protein kinase (MAPK) pathway was evaluated following UBR5 silencing in M2E cells treated with radiation. Increased UBR5 expression was observed in LCC tissues compared with adjacent non-tumor tissues, and it was correlated with poor overall survival of LCC patients. After overexpression or silencing of UBR5 in M2E and M4E LCC cells, cell proliferation and radiosensitivity were significantly increased or decreased, respectively, compared with the control groups. The percentage of S phase cells decreased in the UBR5 si-RNA group compared with that in the control group, while overexpression of UBR5 exerted no effect on the cell cycle. In addition, the expression of Bcl-2 and p38 was decreased in the si-UBR5 combined with radiation groups. The level of phosphorylated p38 expression was increased after combination of si-UBR5 with radiation. The small molecule inhibitor of p38/MAPK signaling, SB203580, decreased the viability of UBR5-overexpressing cells and the survival fraction when cells were exposed to radiation. These findings demonstrated that UBR5 may be involved in regulating cell proliferation and sensitivity to radiotherapy in LCC via the p38/MAPK pathway, thereby highlighting its possible value for the development of new therapeutic strategies and targets for the treatment of this disease.

Altered O-glycosylation is associated with inherent radioresistance and malignancy of human laryngeal carcinoma

Radioresistance (inherent or acquired) remains a major obstacle affecting the clinical outcome of radiotherapy for laryngeal carcinoma. Results from our laboratory and other groups suggest that aberrant glycosylation contributes to cancer acquired radioresistance. However, the role of glycosylation in inherent radioresistance of laryngeal carcinoma has not been fully uncovered. In this study, we investigated the glycan profiling of the inherent radioresistant (Hep-2max) and radiosensitive (Hep-2min) cell lines using lectin microarray analysis. The results revealed that the radioresistant cell line Hep-2max presented higher core 1-type O-glycans than the sensitive one. Further analysis of the O-glycan regulation by benzyl-α-GalNAc application in Hep-2max cells showed partial inhibition of the O-glycan biosynthesis and increased radiosensitivity. In addition, core 1 β1, 3-galactosyltransferase (C1GALT1) overexpression in Hep-2min cells enhanced cell migration, invasion, and radioresistance. Conversely, knockdown of C1GALT1 in Hep-2max cells was able to suppress these malignant phenotypes. Moreover, mechanistic investigations showed that C1GALT1 modified the O-glycans on integrin β1 and regulated its activity. The glycosylation-mediated radioresistance was further inhibited by anti-integrin β1 blocking antibody. Importantly, we also observed that core 1-type O-glycans expression was correlated with advanced tumor stage, metastasis, and poor survival of laryngeal carcinoma patients. These findings suggest that altered O-glycosylation can lead to the inherent radioresistance and progression, and therefore may be important for enhancing the efficacy of radiotherapy in laryngeal carcinoma.

Expressions of CD147, MMP-2 and MMP-9 in Laryngeal Carcinoma and its Correlation with Poor Prognosis

The objectives of this study are to investigate the expressions of matrix metalloproteinase inducing factor (CD147), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) in laryngeal tumor tissues and its significant correlation with tumor infiltration, metastasis and prognosis. Laryngeal tumor tissue from 48 laryngeal cancer patients with complete clinical information was collected. The laryngitis tissue from 15 patients were collected as control group. Immunohistochemical analysis for CD147, MMP-2 and MMP-9 was performed for all the tissue. The results showed the expression rates of CD147, MMP-2 and MMP-9 in laryngeal carcinoma were 87.5 %, 75.0 % and 79.2 % respectively, significantly higher than those (26.7 %, 6.7 %, and 33.3 % respectively) in the control group are (P < 0.01). High expression of CD147, MMP-2 and MMP-9 related to the clinical stages and lymphatic metastasis of laryngeal carcinoma. Univariate survival analysis showed that the 5-year survival of laryngeal carcinoma patients with low expression of CD147, MMP-2 and MMP-9was 83.3 %, 83.3 % and 90 % respectively, while the patients with high expression had 5-year survival at 25 %, 7.7 % and 18.2 % respectively (P < 0.05). Multiple regression analysis showed that high expression of MMP-9 was independently associated with poor prognosis (P < 0.05). High expression of CD147, MMP-2 and MMP-9 were related with laryngeal carcinoma invasion and metastasis. High expressions of CD147, MMP-2 and MMP-9 were all predictive factors of poor prognosis of laryngeal carcinoma.

Reduced expression of mutS homolog 2 and mutL homolog 1 affects overall survival in laryngeal squamous cell carcinoma patients: Investigation into a potential cause

The risk factors affecting the survival rates of laryngeal carcinoma are not well understood. In this study, we investigated the expression status of mutS homolog 2 (MSH2) and mutL homolog 1 (MLH1) and examined the relationship between these two molecules and overall survival rates in laryngeal cancer. We also explored the potential reason for the altered expression of these two genes. Using real-time polymerase chain reaction and western blotting, we detected MSH2 and MLH1 expression in laryngeal cancer tissue samples. We collected a retrospective cohort with 180 laryngeal cancer patients, and inspected MSH2 and MLH1 staining with tissue microarray immunohistochemistry. Prognostic value of clinicopathological characteristics was evaluated by statistical analysis. Laryngeal carcinoma cells were co-cultured with Helicobacter pylori (H. pylori) bacteria. MSH2 and MLH1 were expressed at lower levels compared to those of adjacent tissues in 21 laryngeal carcinoma patients. Patients with negative expression of MSH2 and MLH1 tended to have a higher risk of mortality compared to patients with positive expression (HR=4.38; HR=3.0, respectively). Cigarette smoking rate was higher in the MLH1 expression positive group. H. pylori infection reduced the MSH2 and MLH1 expression levels of laryngeal carcinoma cell lines within co-culture conditions. It is suggested that the altered expression levels of MSH2 and MLH1 probably affect the overall survival of laryngeal carcinoma patients. H. pylori infection may have an effect on the expression of MSH2 and MLH1 in laryngeal carcinoma patients.

Correlation between expression of cellular retinol-binding protein 1 and its methylation status in larynx cancer

AimsThe authors have previously reported that cellular retinol-binding protein 1 (CRBP1) gene gain and its expression correlated significantly with survival in laryngeal carcinoma patients. The authors hypothesised that inactivation of...

Effects of Telomerase Activity on Carcinogenesis and Survival in Laryngeal Carcinoma

This study aimed to look at whether a correlation exists between telomerase activity and survival of laryngeal carcinoma patients. Telomerase activity was measured by telomerase repeat amplification protocol in 31 laryngeal carcinomas and adjacent normal tissues, and in 21 vocal cord polyps (controls). Follow-up was for at least 60 months. Telomerase activity in tissues adjacent to laryngeal carcinomas was significantly higher than in the carcinomas which was, in turn, significantly higher than in vocal cord polyps. There was no significant difference between telomerase activity in carcinomas or adjacent tissues and clinicopathological characteristics. Patients with high telomerase activity in carcinoma tissue had significantly shorter survival times than those with low activity, but no significance difference was observed between survival time and telomerase status in adjacent tissues. Linear regression showed significant association between telomerase activity levels in carcinoma tissues and survival time, but this was not observed in adjacent tissues. This study suggests that telomerase activation probably takes place before the cancer phenotype develops and has prognostic significance for survival of patients with laryngeal carcinoma.

Cell kinetics and apoptosis in laryngeal carcinoma patients.

Cellular proliferation and apoptosis are both implicated in the process of carcinogenesis. The objective of this study was to access the prognostic significance of the expression of proliferating cell nuclear antigen (PCNA) and the apoptosis-related genes (bax, bcl-2, and p53) in laryngeal carcinoma patients. Thirty consecutive patients with stage I to IV squamous cell laryngeal carcinoma were treated in our department from 1992 to 1994. We immunohistochemically studied the expression of PCNA and bax, bcl-2, and p53 genes in their tumor specimens. Five healthy men were used as the control group. The staining results were correlated with clinicopathologic data. The PCNA protein expression was correlated with a significantly worse survival in those patients who were bax-negative (0% versus 42.86%, p = .0445). Similarly, the presence of PCNA led to an unfavorable clinical outcome in those patients who were bax-negative, bcl-2-negative, and p53-negative (0% versus 50%, p = .0278). Expression of bcl-2 protein was found to be an independent prognostic factor related to an unfavorable clinical outcome (p = .0262). The expression of bcl-2 protein appears to predict survival in laryngeal carcinoma patients. Furthermore, the combined study of proliferation markers and apoptosis-related genes helped us to identify a high-risk group of patients who may benefit from a more aggressive treatment protocol.