Proteomics and liquid biopsy characterization of human EMT-related metastasis in colorectal cancer.

Tumor cells undergo epithelial-mesenchymal transition (EMT), however, there is a room of disagreement in role of EMT heterogeneity to colorectal cancer metastasis (mCRC) evolution. To uncover new EMT-related metastasis proteins and pathways, we addressed the EMT status in colorectal cancer liver metastasis patient-derived CTCs to identify proteins that promote their distant metastasis. And then, we performed a comparative proteomic analysis in matched pairs of primary tumor tissues, adjacent mucosa tissues and liver metastatic tissues. By integrative analysis we show that, unstable Epithelial/Mesenchymal (E/M)-type CTCs had the strongest liver metastases formation ability and the proportion of E/M-type CTCs correlated with distant metastases. Using an optimized proteomic workflow including data independent acquisition (DIA) and parallel reaction monitoring (PRM), we identified novel EMT-related protein cluster (GNG2, COL6A1, COL6A2, DCN, COL6A3, LAMB2, TNXB, CAVIN1) and well-described (ERBB2) core protein level changes in EMT-related metastasis progression, and the proteomic data indicate ERBB2, COL6A1 and CAVIN1 are promising EMT-related metastatic biomarker candidates. This study contributes to our understanding of the role that EMT plays in CRC metastasis and identifies heterogeneous EMT phenotypes as a key piece for tumor progression and prognosis. We further propose that therapies targeting this aggressive subset (E/M-type) of CTCs and related protein may be worthy of exploration as potential suppressors of metastatic evolution.

MTUS1 is a promising diagnostic and prognostic biomarker for colorectal cancer.

BACKGROUND: The morbidity and mortality of colorectal cancer (CRC) remain high, posing a serious threat to human life and health. The early diagnosis and prognostic evaluation of CRC are two major challenges in clinical practice. MTUS1 is considered a tumour suppressor and can play an important role in inhibiting cell proliferation, migration, and tumour growth. Moreover, the expression of MTUS1 is decreased in different human cancers, including CRC. However, the biological functions and molecular mechanisms of MTUS1 in CRC remain unclear. METHODS: In the present study, data from The Cancer Genome Atlas (TCGA) database were analysed using R statistical software (version 3.6.3.) to evaluate the expression of MTUS1 in tumour tissues and adjacent normal tissues using public databases such as the TIMER and Oncomine databases. Then, 38 clinical samples were collected, and qPCR was performed to verify MTUS1 expression. We also investigated the relationship between MTUS1 expression and clinicopathological characteristics and elucidated the diagnostic and prognostic value of MTUS1 in CRC. In addition, the correlation between MTUS1 expression and immune infiltration levels was identified using the TIMER and GEPIA databases. Furthermore, we constructed and analysed a PPI network and coexpression modules of MTUS1 to explore its molecular functions and mechanisms. RESULTS: CRC tissues exhibited lower levels of MTUS1 than normal tissues. The logistic regression analysis indicated that the expression of MTUS1 was associated with N stage, TNM stage, and neoplasm type. Moreover, CRC patients with low MTUS1 expression had poor overall survival (OS). Multivariate analysis revealed that the downregulation of MTUS1 was an independent prognostic factor and was correlated with poor OS in CRC patients. MTUS1 expression had good diagnostic value based on ROC analysis. Furthermore, we identified a group of potential MTUS1-interacting proteins and coexpressed genes. GO and KEGG enrichment analyses showed that MTUS1 was involved in multiple cancer-related signalling pathways. Moreover, the expression of MTUS1 was significantly related to the infiltration levels of multiple cells. Finally, MTUS1 expression was strongly correlated with various immune marker sets. CONCLUSIONS: Our results indicated that MTUS1 is a promising biomarker for predicting the diagnosis and prognosis of CRC patients. MTUS1 can also become a new molecular target for tumour immunotherapy.

Primary hepatic non-Hodgkin's lymphoma with rectal cancer: A case report.

Primary hepatic non-Hodgkin's lymphoma (NHL) is an extremely rare disease that is commonly neglected as a possible diagnosis. The present study reports the case of a middle-aged male with chronic hepatitis B in which primary hepatic NHL and rectal cancer occurred simultaneously. A large solitary tumor in the left lobe of the liver was incidentally detected on routine examination prior to the laparoscopic resection of the rectal cancer. Laparoscopic resection of the rectal cancer and a liver biopsy were performed simultaneously. The pathology revealed that the hepatic tumor was NHL and that the rectal cancer was adenocarcinoma. Systemic staging revealed no evidence of nodal or bone marrow involvement, therefore, primary hepatic lymphoma (PHL) was diagnosed. PHL associated with rectal adenocarcinoma is extremely rare and to the best of our knowledge, has never been reported. At present, the cause and most effective therapy for the condition remain unclear.

Adjuvant imatinib for gastrointestinal stromal tumors: the current situation and problems.

OBJECTIVE: To review the current situation and find out the current problems of adjuvant imatinib for gastrointestinal stromal tumors (GISTs). METHODS: Searching for articles and records about imatinib for GISTs, especially adjuvant imatinib for GISTs, on MEDLINE, EMBASE and international conference on gastrointestinal. RESULTS: GISTs are derived from mesenchymal cells of the gastrointestinal tract. The standard treatment for primary GISTs is to resect the tumor together with the negative margins completely without tumor rupture and spillage. Conventional chemotherapy and radiotherapy is ineffective for advanced GISTs. The introduction of imatinib has dramatically changed the natural history of advanced GISTs. Imatinib is generally safe and effective with doses of 400, 600 or 800 mg daily, and has become the standard drug in the treatment for patients with advanced GISTs. Furthermore, most of the toxicity of imatinib is minimal and manageable, almost no treatment-related deaths have been reported. Therefore, adjuvant imatinib therapy is safe and seems to improve recurrence-free survival after the resection of primary GISTs. CONCLUSIONS: Although U.S Food and Drug Administration and European Medicines Agency have approved the use of adjuvant imatinib for GISTs postoperatively, a series of questions about the use of adjuvant imatinib still exist, such as the impact of adjuvant imatinib on overall survival, the optimal dose, the best duration of treatment and the most suitable patients. Doctors and patients should weigh the pros (the decrease of relapse) and cons (drug toxicity and drug costs), especially in terms of the benefit of overall survival.