calpain and Laryngeal-Neoplasms

Recent evidence indicates the involvement of calpains (CAPNs), a family of cysteine proteases, in cancer development and progression, as well as the insufficient response to cancer therapies. The contribution of CAPNs and regulatory calpastatin (CAST) and ERK1/2 kinases to aggressiveness, disease course, and outcome in laryngeal cancer remains elusive. This study was aimed to evaluate the CAPN1/2-CAST-ERK1/2 enzyme system mRNA/protein level and to investigate whether they can promote the dynamic of tumor growth and prognosis. The mRNA expression of marker genes was determined in 106 laryngeal cancer (SCLC) cases and 73 non-cancerous adjacent mucosa (NCLM) controls using quantitative real-time PCR. The level of corresponding proteins was analyzed by Western Blot. SLUG expression, as indicator of pathological advancement was determined using IHC staining. Significant increases of CAPN1/2-CAST-ERK1/2 levels of mRNA/protein were noted in SCLC compared to NCLM (p < 0.05). As a result, a higher level of CAPN1 and ERK1 genes was related to larger tumor size, more aggressive and deeper growth according to TFG scale and SLUG level (p < 0.05). There were also relationships of CAPN1/2 and ERK1 with incidences of local/nodal recurrences (p < 0.05). An inverse association for CAPN1/2, CAST, and ERK1/2 transcripts was determined with regard to overall survival (p < 0.05). In addition, a higher CAPN1 and phospho-ERK1 protein level was related to higher grade and stage (p < 0.05) and was found to promote worse prognosis. This is the first study to show that activity of CAPN1/2- CAST-ERK1/2 axis may be an indicator of tumor phenotype and unfavorable outcome in SCLC.

Topics: Aged; Aged, 80 and over; Calcium-Binding Proteins; Calpain; Disease Progression; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Laryngeal Mucosa; Laryngeal Neoplasms; Male; Middle Aged; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Neoplasm Grading; Neoplasm Recurrence, Local; Phenotype; Prognosis; Risk Factors; RNA, Messenger; Tumor Burden

Laryngeal carcinoma is a common upper respiratory tract cancer with different environmental and genetic factors involved in its development. Calpains are Ca2+-dependent cysteine proteases that modulate cellular function. A novel association between calpain 10 (CAPN10) haplotypes and laryngeal cancer has been found recently. Therefore, the goal of this study was to analyze the contribution of CAPN10 alleles to laryngeal cancer survival.. Patients were recruited from southern Spain. Genotypes were determined using pyrosequencing technology. We analyzed CAPN10 UCSNP-44, UCSNP-43, UCSNP-19, and UCSNP-63 allelic distributions in 199 patients with unrelated laryngeal cancer. Survival curves were calculated from the date of the intervention to the date of death. Multivariate analyses were done using the Cox proportional risk model.. UCSNP-19, UCSNP-43, and UCSNP-44 were unrelated to survival in both univariate and multivariate analyses. However, for UCSNP-63 genotype 12 a significant relationship was observed in multivariate analysis (hazard ratio [HR] = 2.73; 95% confidence interval [CI], 1.21-6.20).. CAPN10 UCSNP-63 genotype 12 seems to be related with a worse prognosis in laryngeal cancer.

Topics: Aged; Alleles; Analysis of Variance; Calpain; Cause of Death; Cohort Studies; Confidence Intervals; DNA, Neoplasm; Female; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Humans; Kaplan-Meier Estimate; Laryngeal Neoplasms; Male; Middle Aged; Multivariate Analysis; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Prognosis; Proportional Hazards Models; Spain; Survival Analysis

Laryngeal carcinoma is a common upper respiratory tract cancer with different environmental and genetic factors involved in its development. To date, CAPN10 has been found to be extensively associated with hyperinsulinaemia and type 2 diabetes mellitus, by different groups. In addition, some reports have shown evidence that hyperinsulinaemia exerts a protective effect on laryngeal cancer risk. On the other hand, low circulating levels of IGF-1 have been recently found in patients with laryngeal carcinoma. Our objective was to examine the contribution of CAPN10 alleles to the development of laryngeal cancer.. Cases and controls were recruited from central and southern Spain. Genotypes were determined using pyrosequencing technology. We analysed CAPN10 UCSNP-44, -43, -19, and -63 allelic distribution in 218 unrelated laryngeal cancer patients and 606 controls from the general population.. We found that the UCSNP-44 allele-C is significantly under-represented among patients with laryngeal cancer (OR=0.685, p=0.02).. These results indicate that some CAPN10 alleles may be exerting a protective effect on laryngeal cancer risk in the Spanish population.

Topics: Alleles; Calpain; Case-Control Studies; Female; Haplotypes; Humans; Laryngeal Neoplasms; Male; Middle Aged; Risk Factors; Spain; White People