APOA5 alleviates reactive oxygen species to promote oxaliplatin resistance in PIK3CA-mutated colorectal cancer.

Although platinum-based chemotherapy is the frontline regimen for colorectal cancer (CRC), drug resistance remains a major challenge affecting its therapeutic efficiency. However, there is limited research on the correlation between chemotherapy resistance and lipid metabolism, including PIK3CA mutant tumors. In this present study, we found that PIK3CA-E545K mutation attenuated cell apoptosis and increased the cell viability of CRC with L-OHP treatment in vitro and in vivo. Mechanistically, PIK3CA-E545K mutation promoted the nuclear accumulation of SREBP1, which promoted the transcription of Apolipoprotein A5 (APOA5). APOA5 activated the PPARγ signaling pathway to alleviate reactive oxygen species (ROS) production following L-OHP treatment, which contributed to cell survival of CRC cells. Moreover, APOA5 overexpression enhanced the stemness-related traits of CRC cells. Increased APOA5 expression was associated with PIK3CA mutation in tumor specimens and poor response to first-line chemotherapy, which was an independent detrimental factor for chemotherapy sensitivity in CRC patients. Taken together, this study indicated that PIK3CA-E545K mutation promoted L-OHP resistance by upregulating APOA5 transcription in CRC, which could be a potent target for improving L-OHP chemotherapeutic efficiency. Our study shed light to improve chemotherapy sensitivity through nutrient management in CRC.

Clinicopathological, Radiological, and Molecular Features of Primary Lung Adenocarcinoma with Morule-Like Components.

BACKGROUND: Morule-like component (MLC) was a rare structure in primary lung adenocarcinoma. We aimed to reveal the clinicopathological, radiological, immunohistochemical, and molecular features of lung adenocarcinoma with MLCs. METHODS: Twenty lung adenocarcinomas with MLCs were collected, and computed tomographic and histological documents were reviewed. Immunohistochemistry, targeted next-generation sequencing, and Sanger sequencing for ß-catenin gene were performed. RESULTS: There were 9 lepidic adenocarcinomas, 8 acinar adenocarcinomas, 2 papillary adenocarcinomas, and 1 minimally invasive adenocarcinoma. Most patients (16/17) were shown a pure solid nodule, and 1 patient was shown a partly solid nodule on chest computed tomography (CT). Nine cases were accompanied with micropapillary components, and 3 were with cribriform components in which 2 suffered a worse prognosis. No significant association was found between the MCLs and the overall survival of lung adenocarcinoma (P = 0.109). The MLCs were often arranged in whorled or streaming patterns. The cells in MLCs showed syncytial and mild appearance. The MLCs were positive for E-cadherin, CK7, TTF-1, napsin-A, vimentin, and ß-catenin (membrane), and negative for CK5/6, p40, p63, Synaptophysin, chromogranin A, and Cdx-2. EGFR mutation, ALK-EML4 fusion, HER2 amplification, and PIK3CA mutation were detected in 16 cases, 2 cases, 1 case, and 1 case, respectively. EGFR mutation was more frequent in adenocarcinomas with MLCs than those without MLCs (P = 0.040). ß-catenin gene mutation was not detected in any patients. CONCLUSIONS: MLC is often observed in the background of acinar, lepidic, and papillary adenocarcinomas. Lung adenocarcinomas with MLCs tend to appear as a solid mass on CT and harbor EGFR gene mutations. The micropapillary components and cribriform components may cause poor prognosis of lung adenocarcinomas with MLCs. Vimentin is always positive in MLCs, and it is a useful marker for the identification of MLCs.

Gastrointestinal-type chemotherapy prolongs survival in an atypical primary ovarian mucinous carcinoma: A case report.

BACKGROUND: Primary ovarian mucinous carcinoma is a rare histologic subtype of epithelial ovarian carcinoma and exhibits considerable morphologic overlap with secondary tumour. It is hard to differentiate primary from metastatic ovarian mucinous carcinoma by morphological and immunohistochemical features. Because of the histologic similarity between primary ovarian mucinous carcinoma and metastatic gastrointestinal carcinoma, it has been hypothesized that ovarian mucinous carcinomas might respond better to non-gynecologic regimens. However, the standard treatment of advanced ovarian mucinous carcinoma has not reached a consensus. CASE SUMMARY: A 56-year-old postmenopausal woman presented with repeated pain attacks in the right lower quadrant abdomen, accompanied by diarrhoea, anorexia, and weight loss for about 3 mo. The patient initially misdiagnosed as having gastrointestinal carcinoma because of similar pathological features. Based on the physical examination, tumour markers, imaging tests, and genetic tests, the patient was clinically diagnosed with ovary mucinous adenocarcinoma. Whether gastrointestinal-type chemotherapy or gynecologic chemotherapy was a favourable choice for patients with advanced ovarian mucinous cancer had not been determined. The patient received a chemotherapy regimen based on the histologic characteristics rather than the tumour origin. The patient received nine cycles of FOLFOX and bevacizumab. This was followed by seven cycles of bevacizumab maintenance therapy for 9 mo. Satisfactory therapeutic efficacy was achieved. CONCLUSION: The genetic analysis might be used in the differential diagnosis of primary ovarian mucinous carcinoma and non-gynecologic mucinous carcinoma. Moreover, primary ovarian mucinous carcinoma patients could benefit from gastrointestinal-type chemotherapy.

MDCT-Based Radiomics Features for the Differentiation of Serous Borderline Ovarian Tumors and Serous Malignant Ovarian Tumors.

OBJECTIVE: To investigate whether multidetector computed tomography (MDCT)-based radiomics features can discriminate between serous borderline ovarian tumors (SBOTs) and serous malignant ovarian tumors (SMOTs). PATIENTS AND METHODS: Eighty patients with SBOTs and 102 patients with SMOTs, confirmed by pathology (training set: n = 127; validation set: n = 55) from December 2017 to June 2020, were enrolled in this study. The interclass correlation coefficient (ICC) and least absolute shrinkage and selection operator (LASSO) regression were applied to select radiomics parameters derived from MDCT images on the arterial phase (AP), venous phase (VP), and equilibrium phase (EP). Receiver operating characteristic (ROC) analysis of each selected parameter was carried out. Heat maps were created to illustrate the distribution of the radiomics parameters. Three models incorporating selected radiomics parameters generated by support vector machine (SVM) classifiers in each phase were analyzed by ROC and compared using the DeLong test. RESULTS: The most predictive features selected by ICC and LASSO regression between SBOTs and SMOTs included 9 radiomics parameters on AP, VP, and EP each. Three models on AP, VP, and EP incorporating the selected features generated by SVM classifiers produced AUCs of 0.80 (accuracy, 0.75; sensitivity, 0.74; specificity, 0.75), 0.86 (accuracy, 0.78; sensitivity, 0.80; specificity, 0.75), and 0.73 (accuracy, 0.69; sensitivity, 0.71; specificity, 0.67), respectively. There were no significant differences in the AUCs among the three models (AP vs. VP, P = 0.199; AP vs. EP, P = 0.260; VP vs. EP, P = 0.793). CONCLUSION: MDCT-based radiomics features could be used as biomarkers for the differentiation of SBOTs and SMOTs.