ABSTRACT
Objective: Anorectal mucosal melanoma is a rare and aggressive cancer with limited treatment options. Investigating specific molecular pathways may provide insight into the development and progression of this cancer. This study aims to investigate the role of chitinase-3-like protein-1 (YKL-40) in promoting the development of anorectal mucosal melanoma through the PI3K-AKT signaling pathway. Methods: Perianal cells from healthy volunteers and melanoma cells from patients with early, middle and advanced anorectal melanoma were obtained. Western blotting was performed to detect the protein expression of PI3K, AKT, and the downstream proteins mTOR, p-mTOR, ERK, and p-ERK, respectively. Subsequently, we constructed knockout and overexpression of YKL-40 melanoma cell lines, then used western blot assay to test for YKL-40, PI3K and AKT protein expression. Results: A significant increase in the expression of PI3K, AKT, and the downstream proteins mTOR, pmTOR, ERK, and pERK was observed in melanoma cells, and the expression of these proteins increased with the development of melanoma. After YKL-40 was knocked out, PI3K and AKT expression decreased in melanoma cells in patients with advanced melanoma. On the contrary, PI3K and AKT protein expression increased significantly after YKL-40 overexpression. Conclusion: There is a positive correlation between the expression levels of PI3K, AKT, mTOR, p-mTOR, ERK, and p-ERK and the stage of tumor development. The PI3K-AKT signaling pathway promotes the progress of anorectal mucosal melanoma. Chitinase-3-like protein-1 (YKL-40) regulates the progression of anorectal mucosal melanoma through the PI3K-AKT signaling pathway. Investigating specific molecular pathways may provide a better understanding of anorectal mucosal melanoma. The findings from this study could contribute to the development of new diagnosis and treatment strategies for this rare and aggressive cancer. Future research directions may include investigating other possible pathways involved in melanoma progression.
Subject(s)
Chitinase-3-Like Protein 1 , Melanoma , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , Humans , Chitinase-3-Like Protein 1/metabolism , Melanoma/genetics , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Male , Cell Line, Tumor , Rectal Neoplasms/pathology , Rectal Neoplasms/metabolism , Rectal Neoplasms/genetics , Anus Neoplasms/genetics , Anus Neoplasms/pathology , Female , Disease Progression , Middle AgedABSTRACT
AIM: Anal melanoma is a rare malignancy with a poor prognosis. METHOD: All patients with a diagnosis of anal melanoma treated at a single institution between 2000 and 2012 were identified and their treatment and outcome were evaluated. RESULTS: Sixteen patients had a median survival of 2.9 years. Fourteen had Stage I or II disease with a median survival of 4.0 years and progression-free survival of 1.5 years. When used for disease staging, whole body positron emission tomography/CT identified an additional three sites of metastasis in five patients compared with CT of the chest, abdomen and pelvis. Surgery involved wide local excision or abdominoperineal excision with respective local recurrence rates of 50% and 66%. Eleven patients underwent testing for c-Kit mutations, of whom five were positive. Four of these were treated with the tyrosine kinase inhibitor imatinib, and showed rapid response of metastases outside the central nervous system. CONCLUSION: The outcome of this malignancy remains poor. PET is the modality of choice for disease staging. Testing tumours for c-Kit mutations may allow selected patients to participate in trials of tyrosine kinase inhibitors.
Subject(s)
Anal Canal/surgery , Antineoplastic Agents/therapeutic use , Anus Neoplasms/therapy , Digestive System Surgical Procedures , Imatinib Mesylate/therapeutic use , Melanoma/therapy , Adult , Aged , Aged, 80 and over , Anal Canal/pathology , Anus Neoplasms/genetics , Anus Neoplasms/mortality , Anus Neoplasms/pathology , Dacarbazine/therapeutic use , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Male , Melanoma/genetics , Melanoma/mortality , Melanoma/pathology , Middle Aged , Mutation , Neoplasm Staging , Niacinamide/analogs & derivatives , Niacinamide/therapeutic use , Phenylurea Compounds/therapeutic use , Proto-Oncogene Proteins c-kit/genetics , Retrospective Studies , Sorafenib , Survival RateABSTRACT
Standard treatment for anal canal cancer is definitive radiochemotherapy (RCT) with 5-fluorouracil plus mitomycin C. Induction chemotherapy, maintenance chemotherapy and replacing mitomycin C with cisplatin proved not to be feasible in phase III trials. New substances such as capecitabine and oxaliplatin have been tested in phase II trials. Because anal cancer overexpresses the epidermal growth factor receptor (EGFR), and a KRAS wild type is usually present, treatment with the EGFR antibody cetuximab is potentially interesting. Phase I trials have shown that the combination with RCT is practicable; however, phase II trials have not yet been carried out.