Survival for patients with osteosarcoma has not improved for > 30 years. Despite aggressive multi-agent chemotherapy combined with surgical resection, a significant fraction of patients with localized disease relapse after optimal treatment. We evaluated the occurrence of cytoplasmic LC3B (light chain 3B)-positive puncta (a marker of autophagy) and presence of HSP27 (heat shock protein 27) in cancer cells within pre-treatment biopsy, post-treatment surgical resection, and metastatic osteosarcoma specimens by immunohistochemistry in 260 patients. LCB3+ puncta expression was seen in 34% of pre-treatment. 50% of resection, and 67% of metastasis samples. Sixty-six percent of all specimens were scored positive for HSP27 (85% of pre-treatment. 52% of resection, and 50% of metastasis samples). Among 215 patients with localized disease, pre-treatment HSP27 expression was associated with inferior overall survival (adjusted HR 26.7, p=0.0263) as well as at resection following chemotherapy (adjusted HR 1.85, p=0.039). Lack of LC3B-puncta expression was an independent poor prognostic marker at resection (adjusted HR 1.75, p=0.045). Patients with LC3B+/HSP27- tumors at resection had the best prognosis whereas patients with LC3B-/HSP27+ osteosarcoma had the worst long-term survival. Neither HSP27 nor LC3B expression correlated with tumor necrosis. These findings indicate that HSP27 expression is a negative prognostic biomarker in osteosarcoma. Conversely, presence of autophagy following neoadjuvant chemotherapy, as measured by LC3B-puncta, predicts longer overall survival in osteosarcoma patients with localized disease.
We additionally evaluated the significance of chemotherapy-induced autophagy in 2 human osteosarcoma cell lines: LM7 and CCH-OS-D. Both doxorubicin (DOX) and cisplatin (CDDP) were found to induce autophagy. In LM7 cells, autophagy inhibition with hydroxychloroquine (HCQ) prior to chemotherapy resulted in a trend towards decreased viability consistent with a cytoprotective role of autophagy. In CCH-OS-D cells, autophagy inhibition prior to DOX significantly decreased chemosensitivity suggesting a cytotoxic role of autophagy in this setting. The post-treatment expression of phosphorylated HSP27 was increased in LM7 and decreased in CCH-OS-D following DOX or CDDP. These findings support a dual role of chemotherapy-induced autophagy and potential application of pHSP27 as a predictive biomarker of autophagy inhibitors in osteosarcoma.
","abstract_html":"<p>Survival for patients with osteosarcoma has not improved for > 30 years. Despite aggressive multi-agent chemotherapy combined with surgical resection, a significant fraction of patients with localized disease relapse after optimal treatment. We evaluated the occurrence of cytoplasmic LC3B (light chain 3B)-positive puncta (a marker of autophagy) and presence of HSP27 (heat shock protein 27) in cancer cells within pre-treatment biopsy, post-treatment surgical resection, and metastatic osteosarcoma specimens by immunohistochemistry in 260 patients. LCB3+ puncta expression was seen in 34% of pre-treatment. 50% of resection, and 67% of metastasis samples. Sixty-six percent of all specimens were scored positive for HSP27 (85% of pre-treatment. 52% of resection, and 50% of metastasis samples). Among 215 patients with localized disease, pre-treatment HSP27 expression was associated with inferior overall survival (adjusted HR 26.7, <em>p=</em>0.0263) as well as at resection following chemotherapy (adjusted HR 1.85, <em>p=</em>0.039). Lack of LC3B-puncta expression was an independent poor prognostic marker at resection (adjusted HR 1.75, <em>p=</em>0.045). Patients with LC3B+/HSP27- tumors at resection had the best prognosis whereas patients with LC3B-/HSP27+ osteosarcoma had the worst long-term survival. Neither HSP27 nor LC3B expression correlated with tumor necrosis. These findings indicate that HSP27 expression is a negative prognostic biomarker in osteosarcoma. Conversely, presence of autophagy following neoadjuvant chemotherapy, as measured by LC3B-puncta, predicts longer overall survival in osteosarcoma patients with localized disease.</p> <p>We additionally evaluated the significance of chemotherapy-induced autophagy in 2 human osteosarcoma cell lines: LM7 and CCH-OS-D. Both doxorubicin (DOX) and cisplatin (CDDP) were found to induce autophagy. In LM7 cells, autophagy inhibition with hydroxychloroquine (HCQ) prior to chemotherapy resulted in a trend towards decreased viability consistent with a cytoprotective role of autophagy. In CCH-OS-D cells, autophagy inhibition prior to DOX significantly decreased chemosensitivity suggesting a cytotoxic role of autophagy in this setting. The post-treatment expression of phosphorylated HSP27 was increased in LM7 and decreased in CCH-OS-D following DOX or CDDP. These findings support a dual role of chemotherapy-induced autophagy and potential application of pHSP27 as a predictive biomarker of autophagy inhibitors in osteosarcoma.</p>","abstract_has_math":false,"creators":["Livingston, John Andrew","0000-0002-1337-3282
"],"institution":null,"degree_name":"Masters of Science (MS)","degree_level":"Thesis (MS)","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Eugenie S. Kleinerman","Patrick Hwu","Robert Bast Jr."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2017,"date_issued":"2017-08-01T07:00:00Z","date_published":"2017-08-01T07:00:00Z","updated_at":"2026-07-24T05:50:38Z","subjects":["Osteosarcoma","autophagy","heat shock protein","biomarkers","LC3B","HSP27","Medicine and Health Sciences","Oncology"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/798","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Eugenie S. Kleinerman","Patrick Hwu","Robert Bast Jr."]},{"key":"dc:creator","label":"Author","values":["Livingston, John Andrew","0000-0002-1337-3282
"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2018-02-09T08:00:00Z"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis (MS)"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Masters of Science (MS)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Osteosarcoma","autophagy","heat shock protein","biomarkers","LC3B","HSP27","Medicine and Health Sciences","Oncology"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/798"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Survival for patients with osteosarcoma has not improved for > 30 years. Despite aggressive multi-agent chemotherapy combined with surgical resection, a significant fraction of patients with localized disease relapse after optimal treatment. We evaluated the occurrence of cytoplasmic LC3B (light chain 3B)-positive puncta (a marker of autophagy) and presence of HSP27 (heat shock protein 27) in cancer cells within pre-treatment biopsy, post-treatment surgical resection, and metastatic osteosarcoma specimens by immunohistochemistry in 260 patients. LCB3+ puncta expression was seen in 34% of pre-treatment. 50% of resection, and 67% of metastasis samples. Sixty-six percent of all specimens were scored positive for HSP27 (85% of pre-treatment. 52% of resection, and 50% of metastasis samples). Among 215 patients with localized disease, pre-treatment HSP27 expression was associated with inferior overall survival (adjusted HR 26.7, p=0.0263) as well as at resection following chemotherapy (adjusted HR 1.85, p=0.039). Lack of LC3B-puncta expression was an independent poor prognostic marker at resection (adjusted HR 1.75, p=0.045). Patients with LC3B+/HSP27- tumors at resection had the best prognosis whereas patients with LC3B-/HSP27+ osteosarcoma had the worst long-term survival. Neither HSP27 nor LC3B expression correlated with tumor necrosis. These findings indicate that HSP27 expression is a negative prognostic biomarker in osteosarcoma. Conversely, presence of autophagy following neoadjuvant chemotherapy, as measured by LC3B-puncta, predicts longer overall survival in osteosarcoma patients with localized disease.
We additionally evaluated the significance of chemotherapy-induced autophagy in 2 human osteosarcoma cell lines: LM7 and CCH-OS-D. Both doxorubicin (DOX) and cisplatin (CDDP) were found to induce autophagy. In LM7 cells, autophagy inhibition with hydroxychloroquine (HCQ) prior to chemotherapy resulted in a trend towards decreased viability consistent with a cytoprotective role of autophagy. In CCH-OS-D cells, autophagy inhibition prior to DOX significantly decreased chemosensitivity suggesting a cytotoxic role of autophagy in this setting. The post-treatment expression of phosphorylated HSP27 was increased in LM7 and decreased in CCH-OS-D following DOX or CDDP. These findings support a dual role of chemotherapy-induced autophagy and potential application of pHSP27 as a predictive biomarker of autophagy inhibitors in osteosarcoma.
"]},{"key":"dc:title","label":"Title","values":["Hsp27 and Chemotherapy-Induced Autophagy As Biomarkers In Osteosarcoma"]}]}],"canonical_facts":{"dc:contributor":["Eugenie S. Kleinerman","Patrick Hwu","Robert Bast Jr."],"dc:creator":["Livingston, John Andrew","0000-0002-1337-3282
"],"dc:date.available":["2018-02-09T08:00:00Z"],"dc:description.abstract":["Survival for patients with osteosarcoma has not improved for > 30 years. Despite aggressive multi-agent chemotherapy combined with surgical resection, a significant fraction of patients with localized disease relapse after optimal treatment. We evaluated the occurrence of cytoplasmic LC3B (light chain 3B)-positive puncta (a marker of autophagy) and presence of HSP27 (heat shock protein 27) in cancer cells within pre-treatment biopsy, post-treatment surgical resection, and metastatic osteosarcoma specimens by immunohistochemistry in 260 patients. LCB3+ puncta expression was seen in 34% of pre-treatment. 50% of resection, and 67% of metastasis samples. Sixty-six percent of all specimens were scored positive for HSP27 (85% of pre-treatment. 52% of resection, and 50% of metastasis samples). Among 215 patients with localized disease, pre-treatment HSP27 expression was associated with inferior overall survival (adjusted HR 26.7, p=0.0263) as well as at resection following chemotherapy (adjusted HR 1.85, p=0.039). Lack of LC3B-puncta expression was an independent poor prognostic marker at resection (adjusted HR 1.75, p=0.045). Patients with LC3B+/HSP27- tumors at resection had the best prognosis whereas patients with LC3B-/HSP27+ osteosarcoma had the worst long-term survival. Neither HSP27 nor LC3B expression correlated with tumor necrosis. These findings indicate that HSP27 expression is a negative prognostic biomarker in osteosarcoma. Conversely, presence of autophagy following neoadjuvant chemotherapy, as measured by LC3B-puncta, predicts longer overall survival in osteosarcoma patients with localized disease.
We additionally evaluated the significance of chemotherapy-induced autophagy in 2 human osteosarcoma cell lines: LM7 and CCH-OS-D. Both doxorubicin (DOX) and cisplatin (CDDP) were found to induce autophagy. In LM7 cells, autophagy inhibition with hydroxychloroquine (HCQ) prior to chemotherapy resulted in a trend towards decreased viability consistent with a cytoprotective role of autophagy. In CCH-OS-D cells, autophagy inhibition prior to DOX significantly decreased chemosensitivity suggesting a cytotoxic role of autophagy in this setting. The post-treatment expression of phosphorylated HSP27 was increased in LM7 and decreased in CCH-OS-D following DOX or CDDP. These findings support a dual role of chemotherapy-induced autophagy and potential application of pHSP27 as a predictive biomarker of autophagy inhibitors in osteosarcoma.
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/798"],"dc:subject":["Osteosarcoma","autophagy","heat shock protein","biomarkers","LC3B","HSP27","Medicine and Health Sciences","Oncology"],"dc:title":["Hsp27 and Chemotherapy-Induced Autophagy As Biomarkers In Osteosarcoma"],"thesis:degree_level":["Thesis (MS)"],"thesis:degree_name":["Masters of Science (MS)"]},"updated_at":"2026-07-24T05:50:38Z"}