Metastatic Colon Adenocarcinoma Research Articles

Seminal vesicle metastasis from transverse colon adenocarcinoma: a unique case report

Summary Background Seminal vesicle metastasis from colon adenocarcinoma is very rare, with only two case reports in the literature. Also, positron emission tomography/computed tomography (PET/CT) imaging in the diagnosis of seminal vesicle tumors seems to have a promising role in its detection, but there have been few reports about its use, in part due to the rarity of the disease. Case presentation We report the case of a 64-year-old male patient with colon adenocarcinoma who at 6 years after the diagnosis presented with metastasis to the seminal vesicles, which responded remarkably to chemotherapy, but 2 years later had a relapse at the seminal vesicles. Imaging with PET/CT was helpful for the diagnosis of this case. Conclusion Our case is unique, as there are no previous reports in the literature on the relapse of metastatic colon adenocarcinoma in the seminal vesicles. Imaging with PET/CT showed compromise of the seminal vesicles in our case; hence, this imaging technique seems to have a promising role in detecting metastatic seminal vesicle tumors.

A Novel Trypsin Kunitz-Type Inhibitor from Cajanus cajan Leaves and Its Inhibitory Activity on New Cancer Serine Proteases and Its Effect on Tumor Cell Growth.

A novel trypsin inhibitor from Cajanus cajan (TIC) fresh leaves was partially purified by affinity chromatography. SDS-PAGE revealed one band with about 15kDa with expressive trypsin inhibitor activity by zymography. TIC showed high affinity for trypsin (Ki = 1.617μM) and was a competitive inhibitor for this serine protease. TIC activity was maintained after 24h of treatment at 70°C, after 1h treatments with different pH values, and β-mercaptoethanol increasing concentrations, and demonstrated expressive structural stability. However, the activity of TIC was affected in the presence of oxidizing agents. In order to study the effect of TIC on secreted serine proteases, as well as on the cell culture growth curve, SK-MEL-28 metastatic human melanoma cell line and CaCo-2 colon adenocarcinoma was grown in supplemented DMEM, and the extracellular fractions were submitted salting out and affinity chromatography to obtain new secreted serine proteases. TIC inhibited almost completely, 96 to 89%, the activity of these serine proteases and reduced the melanoma and colon adenocarcinoma cells growth of 48 and 77% respectively. Besides, it is the first time that a trypsin inhibitor was isolated and characterized from C. cajan leaves and cancer serine proteases were isolated and partial characterized from SK-MEL-28 and CaCo-2 cancer cell lines. Furthermore, TIC shown to be potent inhibitor of tumor protease affecting cell growth, and can be one potential drug candidate to be employed in chemotherapy of melanoma and colon adenocarcinoma.

Use of Immunohistochemical Markers in Differentiation of Hepatocellular Carcinoma from Intrahepatic Cholangiocarcinoma and Metastatic Adenocarcinomatous Deposits in the Liver from Colon: A Cross-sectional Study

Introduction: Hepatocellular Carcinoma (HCC) is a major worldwide health problem due to its high incidence and mortality rates. The liver often becomes a site for metastasis from various primary locations, benefiting from its abundant blood supply. Distinguishing liver metastatic tumours from HCC can pose a diagnostic challenge, significantly impacting prognosis and treatment decisions. Aim: To differentiate between HCC, Intrahepatic Cholangiocarcinoma (ICC), and metastatic colonic adenocarcinoma in the liver using Hep par-1, Cytokeratin (CK) 7, CK19, and CK20 as immunohistochemical markers. The manual Tissue Microarray (TMA) technique was employed for present study. Materials and Methods: The present cross-sectional study was conducted in Department of Pathology at Government Stanley Medical College, Chennai, Tamil Nadu, India, spanning a three-year duration from July 2012 to June 2015. A total of 60 cases diagnosed histologically with HCC, ICC, and metastatic colonic adenocarcinoma in the liver were included. The manual TMA technique was used to create recipient blocks, and immunohistochemistry was performed to assess the expression of Hep par-1, CK7, CK19 and CK20. The sensitivity, specificity, Positive Predictive Value (PPV), and Negative Predictive Values (NPV) of these markers in HCC, ICC, and metastatic colonic adenocarcinoma in the liver were analysed and tabulated using statistical software Statistical Package for Social Sciences (SPSS) version 16.0. Results: The study included a total of 60 cases, with 40 (66.7%) males and 20 (33.3%) females, ranging in age from 27 to 73 years with a mean age of 51.3 years. Among the cases, there were 30 (50%) cases of HCC, 14 (23%) cases of ICC, and 16 (27%) cases of metastatic colonic adenocarcinoma in the liver. The sensitivity, specificity, and PPV of Hep par-1 in distinguishing HCC from ICC and metastatic deposits were 80%, 100%, and 100%, respectively. The NPV of Hep par-1 in distinguishing HCC from ICC and metastatic deposits was 70% and 72%, respectively. The sensitivity, specificity, PPV, and NPV of CK7 in distinguishing ICC from HCC were 3.3%, 50%, 6.3%, and 34.1%, respectively. The sensitivity, specificity, PPV, and NPV of CK19 in distinguishing HCC from ICC and metastatic deposits were 0%, 50%, 0%, and 33.3%. The sensitivity, specificity, PPV, and NPV of CK20 in distinguishing HCC from ICC and metastatic deposits were 0%, 53.3%, 0%, and 34.8%, respectively. Conclusion: In conclusion, it was found that a panel of markers including Hep par-1, CK7, CK19 and CK20 can differentiate between HCC, ICC, and metastatic colonic adenocarcinoma in the liver. This differentiation is crucial for determining the appropriate treatment for patients by understanding the exact behaviour of the tumour.

An Exceptional Rarity: Coexisting Amebic Enterocolitis and Metastatic Colon Adenocarcinoma Deceptively Resembling Crohn's Disease Grossly

Abstract Introduction/Objective Amebiasis is a parasitic infection that is rare in developed countries but mimic crohn’s disease or colon malignancy. Amoeboma of the large intestine, a subtype of amebiasis, is an even rarer condition that can be challenging to differentiate from colorectal carcinoma. While co-occurrence of these two conditions is exceedingly rare, we present a unique case of severe fulminant necrotizing colitis with perforation, which coexisted with metastatic colon adenocarcinoma. Methods/Case Report A 54-year-old female with no travel history, recently diagnosed with sigmoid colon cancer and liver metastasis, presented with acute worsening of her chronic abdominal pain. Upon examination, a sigmoid/rectal mass with local invasion of the bladder and left salpinx, along with liver metastases, was discovered. The patient underwent an emergent exploratory laparotomy, total abdominal colectomy, and end ileostomy due to concerns for perforation. The colon's mucosa displayed a cobblestone-like appearance with diffusely raised tan areas, erosions, exudate, and intervening brown mucosa (Figure 1). Microscopic examination revealed amebic trophozoites invading submucosa diffusely with ingested RBCs in cytoplasm, small round nucleus with dot-like karyosome (figure 2), involving the colon and attached terminal ileum, with perforations in the terminal ileum and ascending colon. The trophozoites were further confirmed by negative CD68 stain, and strongly PAS stain. Additionally, metastatic adenocarcinoma (figure 3-5) was found in two lymph nodes, along with tumor deposits in the mesenteric fat, but no primary adenocarcinoma was identified despite extensive search and sampling. Postoperatively, the patient completed an antibiotic course for Entamoeba, with a smaller lesion near the gallbladder responded, the hepatic lesion remained unchanged, indicating metastatic disease. Results (if a Case Study enter NA) NA Conclusion Although the colectomy specimen's gross findinds initially suggested Crohn's disease, the overall microscopic features favored amebic colitis due to the presence of numerous amebic trophozoites and the patient's lack of IBD history.This case highlights the potential coexistence of colonic amebiasis and colorectal carcinoma, which can mimic each other. This case serves as a reminder to avoid delayed diagnosis and treatment of ameboma infection in patients with colon malignancy history, even in non-endemic countries like the United States. .

S2410 Case Report: Non-Healing Buccal Mucosa Lesion: Atypical Presentation of Metastatic Colon Adenocarcinoma

S2410 Case Report: Non-Healing Buccal Mucosa Lesion: Atypical Presentation of Metastatic Colon Adenocarcinoma

Hidden colon adenocarcinoma diagnosed from mouth metastasis: case report and literature review

BackgroundWe report an unusual case of metastatic colon adenocarcinoma to the maxilla as an initial clinical sign of the disease, this being the second case reported in the palate. In addition, we show an extensive review of the literature, with clinical cases of adenocarcinoma with metastasis to the mouth.Case presentationAn 80-year-old man complained of “swelling on the palate” with a 3-week evolution time. He reported suffering from constipation and high blood pressure. The intraoral examination revealed a pedunculated, red, and painless nodule on the maxillary gingiva. Under the diagnostic hypotheses of squamous cell carcinoma and malignant neoplasm of the salivary gland, an incisional biopsy was performed. Microscopically, the columnar epithelium was observed forming papillary areas, neoplastic cells with prominent nucleoli, hyperchromatic nuclei, atypical mitotic figures, and mucous cells, being positive for CK 20, suggesting the provisional diagnosis of metastatic adenocarcinoma, probably of gastrointestinal origin. The patient was submitted to endoscopy and colonoscopy exams, and a lesion in the sigmoid region of the colon was observed. After a colon biopsy, a moderately differentiated adenocarcinoma was confirmed, establishing the final diagnosis of metastatic neoplasia of colon adenocarcinoma to the oral lesion. The literature review revealed 45 clinical cases of colon adenocarcinoma with metastasis to the oral cavity. To the best of our knowledge, it is the second case on the palate.ConclusionsColon adenocarcinoma with metastasis to the oral cavity is rare but should be included in the differential diagnosis of neoplasms of the oral cavity, even when there are no known primary tumors in some cases, and this may be the first indication of the presence of a tumor.

Long-Term Response to Sintilimab, Bevacizumab and Chemotherapy in Heavily Pretreated Microsatellite Stable Colon Cancer

Most advanced colorectal cancer patients with proficient DNA mismatch repair or microsatellite stability (MSS) are insensitive to immune checkpoint inhibitor therapy. This report describes a heavily pretreated refractory colon adenocarcinoma patient with MSS. After experiencing four lines of treatment, the patient received the fifth-line therapy with the combined sintilimab, bevacizumaband chemotherapy. She achieved a long-term clinical outcome. The patient's progression-free survival after the fifth-line therapy was approximately 9.3months, and her overall survival was approximately 57months. To the best of our knowledge, this case represents the first report of durable clinical benefit from combination of animmune checkpoint inhibitor, bevacizumab and chemotherapy in a heavily pretreated patient with refractory metastatic colon adenocarcinoma with MSS.

Cetuximab-induced Facial Hypertrichosis in a Female Patient Treated for Metastatic Colon Adenocarcinoma

Cetuximab-induced Facial Hypertrichosis in a Female Patient Treated for Metastatic Colon Adenocarcinoma

New Oxazolo[5,4-d]pyrimidines as Potential Anticancer Agents: Their Design, Synthesis, and In Vitro Biological Activity Research.

Cancer is a large group of diseases in which the rapid proliferation of abnormal cells generally leads to metastasis to surrounding tissues or more distant ones through the lymphatic and blood vessels, making it the second leading cause of death worldwide. The main challenge in designing a modern anticancer therapy is to develop selective compounds that exploit specific molecular targets. In this work, novel oxazolo[5,4-d]pyrimidine derivatives were designed, synthesized, and evaluated in vitro for their cytotoxic activity against a panel of four human cancer cell lines (lung carcinoma: A549, breast adenocarcinoma: MCF7, metastatic colon adenocarcinoma: LoVo, primary colon adenocarcinoma: HT29), along with their P-glycoprotein-inhibitory ability and pro-apoptotic activity. These oxazolo[5,4-d]pyrimidine derivatives, which are structurally similar to nucleic purine bases in general, are characterized by the presence of a pharmacologically favorable isoxazole substituent at position 2 and aliphatic amino chains at position 7 of the condensed heterocyclic system. In silico analysis of the obtained compounds identified their potent inhibitory activity towards human vascular endothelial growth factor receptor-2 (VEGFR-2). Molecular docking was performed to assess the binding mode of new derivatives to the VEGFR-2 active site. Then, their physicochemical, pharmacokinetic, and pharmacological properties (i.e., ADME—administration, distribution, metabolism, and excretion) were also predicted to assess their druglikeness. In particular, compound 3g (with a 3-(N,N-dimethylamino)propyl substituent) was found to be the most potent against the HT29 cell line, with a 50% cytotoxic concentration (CC50) of 58.4 µM, exceeding the activity of fluorouracil (CC50 = 381.2 μM) and equaling the activity of cisplatin (CC50 = 47.2 µM), while being less toxic to healthy human cells (such as normal human dermal fibroblasts (NHDFs)) than these reference drugs. The results suggest that compound 3g is a potentially promising candidate for the treatment of primary colorectal cancer.

S2253 Aggressive Metastatic Adenocarcinoma of Colon in Young Hispanic Female Masquerading as Skull Base Osteomyelitis

S2253 Aggressive Metastatic Adenocarcinoma of Colon in Young Hispanic Female Masquerading as Skull Base Osteomyelitis

Oncocytic nodular hyperplasia of the thyroid

Nodular hyperplasia of the thyroid is a process whereby the gland experiences growth by nodular expansion of thyroid parenchyma. We have encountered 45 patients in whom the process was caused by the growth of well-defined and sharply circumscribed but unencapsulated nodules composed of oncocytic thyroid follicular cells. The lesions arose in 39 women and 6 men, aged 25–69 years (mean = 50.3 years). The surrounding thyroid parenchyma showed features of chronic lymphocytic thyroiditis. The nodules varied from microscopic to 5 cm and appeared to compress the surrounding thyroid parenchyma. Most of the lesions lacked a well-defined capsule. In 26 tumors, the nodules displayed a predominantly follicular pattern of growth; in 8 cases there were admixtures of follicular and trabecular patterns with focal solid areas devoid of follicles. Clinical follow-up in 39 patients ranging from 7 to 22 years (median = 16 years) showed no evidence of recurrence, metastasis, or malignant transformation. One patient died of unknown causes 15 years after the diagnosis, and another patient died 4 years after diagnosis from metastatic colonic adenocarcinoma. Oncocytic nodular hyperplasia is a benign process associated with chronic lymphocytic thyroiditis that should be distinguished from benign and malignant oncocytic (Hurthle cell) tumors of the thyroid.

Computational analysis of G-protein-coupled receptor kinase family members as potential targets for colorectal cancer therapy

BackgroundG-protein-coupled receptor (GPCR) kinases (GRKs) interact with ligand-activated GPCR, causing intracellular phosphorylation and interfering with the intracellular signal transduction associated with the development of cancer. Colorectal cancer (CRC) is a fast-growing disease, and its molecular mechanism involves various regulatory proteins, including kinases. However, the GRK mechanism in CRC has not been explored.MethodsWe used an integrated computational approach to investigate the potential of GRK family members as targeted proteins in CRC. The GRK expression levels in tumor and normal tissues, colon adenocarcinoma samples, and metastatic colon adenocarcinoma were analyzed using ONCOMINE, GEPIA, and UALCAN, as well as TNM plots. Genetic changes in the GRK family genes were investigated using cBioportal. The prognostic value related to the gene expression of the GRK family was examined using GEPIA and UALCAN. Co-expression analysis of the GRK family was conducted using COXPRESdb. Association analysis of the Gene Ontology, KEGG pathway enrichment, and drug-gene analyses were performed using the over-representation analysis (ORA) in WebGestalt.ResultsGRK2, GRK3, and GRK5 mRNA levels increased significantly in patients with CRC and metastatic CRC. Genetic changes were detected in patients with CRC, including GRK7 (1.1%), GRK2 (1.7%), GRK4 (2.3%), GRK5 (2.5%), GRK6 (2.5%), GRK3 (2.9%), and GRK1 (4%). CRC patients with low mRNA of GRK7 levels had better disease-free and overall survival than those with high GRK7 levels. Hierarchical clustering analysis revealed significant positive correlations between GRK5 and GRK2 and between GRK2 and GRK6. KEGG pathway enrichment analysis showed that the gene network (GN) regulated several cellular pathways, such as the morphine addiction signaling and chemokine signaling pathways in cancer. The drug-gene association analysis indicated that the GN was associated with several drugs, including reboxetine, pindolol, beta-blocking agents, and protein kinase inhibitors.ConclusionNo research has been conducted on the relation of GRK1 and GRK7 to cancer, particularly CRC. In this work, genes GRK2, GRK3, GRK5, and GRK6 were found to be oncogenes in CRC. Although inhibitors against GRK2, GRK5, and GRK6 have previously been developed, further research, particularly preclinical and clinical studies, is needed before these agents may be used to treat CRC.

The elevated D-2-hydroxyglutarate level found as a characteristic metabolic change of colon cancer in both in vitro and in vivo models

The D-2-hydroxyglutarate (D-2-HG), whose normal cellular concentration is low, can be accumulated 10–100 times natural levels in some cancer types and participates in the carcinogenesis process. D-2-HG is produced by different pathways specific to cancer type. In this study, the level of significant metabolites produced in some metabolic pathways related to D-2-HG in the energy metabolism was determined in colon adenocarcinoma cell lines at different stages. Then, the differences in TCA and Cori cycle, glutaminolysis, and Glycolysis were investigated in the brain, colon, liver, and tumor tissues extracted from xenograft models. The levels of glucose, pyruvate, lactate, all TCA cycle intermediates, and D-2-HG were determined by the HPLC analysis, DNS method, and pyruvate assay. The intracellular D-2-HG level was found at 22.6 μmol/mg in primary (Caco-2) and 152.6 μmol/mg in metastatic (SW620) colon adenocarcinoma cells, whereas it could not be detected in colon epithelial cell line (CCD-18Co). In the xenograft models, D-2-HG could not be detected in CCD-18Co colon and brain tissues, whereas it was produced in Caco-2 and SW620 tissues. Most importantly, the level of D-2-HG was 7.4 and 19.9-fold increased in Caco-2 and SW620 tumor tissues compared to healthy tissue, respectively. In addition, the D-2-HG production pathways were investigated. The results revealed that the carbon source of D-2-HG is glucose, and the imbalance of wt-IDH1/2 enzymes plays a role in its production. Overall, the in vitro and in vivo results show that the enhanced production of endogenous D-2-HG is a characteristic change in the metabolism of colon cancer.

ORAL METASTASIS OF COLONIC ADENOCARCINOMA: A CASE REPORT

A 49-year-old female patient presented with a lobulated reddish swelling on the posterior lower gingiva, causing mobility of the lower second molar and facial asymmetry. The patient's medical history included advanced-staged colonic adenocarcinoma diagnosed 3 months earlier. Panoramic radiography showed a well-defined cortical radiolucent defect measuring 3 cm in the posterior mandible. An incisional biopsy was performed, and macroscopic examination revealed a polypoid soft tissue of fibrous consistency and a whitish homogenous cut surface. Microscopically, glandular tubular structures composed of simple columnar epithelial cells were observed, which were positive for CK20 and negative for CK7, confirming the diagnosis of metastatic colonic adenocarcinoma to the oral cavity. The patient underwent chemotherapy and radiotherapy, but she died after 5 months. Intestinal adenocarcinomas may metastasize to the oral cavity as a gingival swelling in middle-aged adults with a previous malignancy and is diagnosed through the correlation of history, clinical, and immunohistochemical findings.

Stimulated Raman Histology for Rapid Intra-Operative Diagnosis of Sinonasal and Skull Base Tumors.

Intra-operative stimulated Raman histology (SRH) is a novel technology that uses laser spectroscopy and color-matching algorithms to create images similar to the formalin-fixed paraffin-embedded (FFPE) section. We aim to assess the accuracy of SRH in a novel range of sinonasal and skull base tumors. Select patients undergoing sinonasal and skull base surgery using the Invenio Imaging™ Nio™ Laser Imaging SRH system between June 2020 and September 2021 were assessed. The SRH images were reviewed for pathologic features similar to frozen section (FS) and FFPE. Time taken for results and diagnostic concordance was assessed. Sixty-seven SRH images from 7 tumor types in 12 patients were assessed. Pathologies included squamous cell carcinoma, rhabdomyosarcoma, inverted papilloma, adenoid cystic carcinoma, SMARCB1-deficient sinonasal carcinoma, mucosal melanoma, metastatic colonic adenocarcinoma, and meningioma. Tumor was identified in 100% of lesional specimens, with characteristic diagnostic features readily appreciable on SRH. Median time for diagnosis was significantly faster for SRH (4.3 min) versus FS (44.5 min; p=<.0001). Where SRH sample site matched precisely to FS (n=32/67, 47.8%), the same diagnosis was confirmed in 93.8%. Sensitivity, specificity, precision, and overall accuracy of SRH were 93.3%, 94.1%, 93.8%, and 93.3%, respectively. Near-perfect concordance was seen between SRH and FS (Cohen's kappa [κ]=0.89). Stimulated Raman histology can rapidly produce images similar to FFPE H&E in sinonasal and skull base tumors. This technology has the potential to act as an adjunct or alternative to standard FS. 4 Laryngoscope, 132:2142-2147, 2022.

Primary Penile Squamous Cell Carcinoma in a Patient with Metastatic Adenocarcinoma of Colon to Liver: A Case Report

Penile squamous cell carcinoma (SCC) is a rare malignancy associated with human papillomavirus and immunosuppression. If not detected early in its course, local invasion and metastasis to distant regions often occurs. Colorectal adenocarcinoma (CRAC) is the third most common malignancy worldwide. Many familial genetic mutations are associated with CRAC; however, co-presentation with penile SCC has not been established in literature. The authors present a case in which a patient presenting with a primary diagnosis of penile SCC was found to have distant liver metastases due to a previously unknown recurrence of CRAC. The authors conclude that primary penile cancer with subsequent metastatic colon adenocarcinoma is possible in patients with unknown genetic predisposition.

Value of albumin RNAscope in situ hybridization in diagnosis and differential diagnosis of hepatocellular carcinoma

Objective: To investigate the utility of albumin RNAscope in situ hybridization in the diagnosis and differential diagnosis of hepatocellular carcinoma and its mimics. Methods: One hundred and fifty-two cases of hepatocellular carcinoma and its mimics and 33 cases of normal tissue were selected from the pathology database of the Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January 2013 to December 2019. Tissue microarrays were constructed and RNAscope in situ hybridization was performed to detect the expression of albumin mRNA. Results: No albumin mRNA expression was detected in normal tissues except for the liver. All hepatocellular carcinoma regardless of its degree of differentiation and primary or metastatic nature had detectable albumin mRNA, with strong and diffuse staining in 90.7% (49/54) of cases. While the positive rate of HepPar-1, Arg-1 or one of them by immunohistochemistry was 87.0% (47/54), 85.2% (46/54) and 92.6% (50/54) respectively. The positive rates of albumin mRNA in intrahepatic cholangiocarcinoma and biphenotypic hepatocellular carcinoma were 7/15 and 9/10, respectively. The former showed focal or heterogeneous staining, while the latter showed strong and diffuse staining. The positive rate of hepatoid adenocarcinoma was 8/19, and the albumin expression could be diffuse or focal. Sporadic cases of poorly differentiated gastric adenocarcinoma and metastatic colon adenocarcinoma showed focal staining of albumin mRNA. Conclusions: Detection of albumin mRNA by RNAscope in situ hybridization is of great value for the diagnosis and differential diagnosis of HCC, and the sensitivity may be improved by combining with HepPar-1 and Arg-1. It also offers different diagnostic clues according to different expression patterns.

Successful infusional 5-fluorouracil administration in a patient with vasospastic angina

A 48-year-old female with metastatic colon adenocarcinoma and history of pre-existing coronary vasospasm with ventricular tachycardia (VT) successfully tolerated de novo 5-fluorouracil (5-FU) chemotherapy infusions with prophylactic administration and optimization of anti-spasm medications. 5-FU has been reported to produce severe cardiotoxic side effects, including coronary vasospasm, ventricular arrhythmias, and sudden cardiac death, and is not typically reported in individuals with pre-existing coronary vasospasm.

CBX3 is associated with metastasis and glutathione/glycosphingolipid metabolism in colon adenocarcinoma

Metastasis is the major cause of colon adenocarcinoma (COAD) mortality. Increasing studies demonstrated that the epigenetics and downstream expression change of pivotal genes may act as a major role in promoting COAD progression and metastasis. Therefore, identifying the dysregulation of key genes associating with COAD metastasis may provide a new strategy for the discovery of potential treatment targets. This study included a single-cell RNA sequencing profile consisting of 17,469 tumor cells derived from 23 samples, and 326 COADs available from The Cancer Genome Atlas (TCGA), etc. The study was performed using comparative analysis to characterize the role of CBX3 in COAD metastasis and progression. This study revealed that the mRNA level of Chromebox homolog 3 (CBX3) in the metastatic COAD was significantly higher than that of the primary COAD and normal colon tissues (Wilcoxon's rank-sum test, P<0.05). Activation of CBX3 was involved in regulating an interaction network consisting of CCT6A, LSM5, and GGCT, etc., which may subsequently participate in glutathione metabolism. Besides, CBX3 also exhibited a negative correlation with glycosphingolipid metabolism, which may associate with the regulation of CBX3 on DNA methylation. Clinical data analysis demonstrated that patients with high CBX3 mRNA levels showed a nearly 2-fold shorter overall survival time than the control group (hazard ratio =1.59; likelihood ratio test, P=0.04). Our study demonstrated that CBX3 overexpression is associated with COAD metastasis. CBX3 downstream regulation network involves in TCP1 complex, LSM family, and glutathione metabolism, which may provide a potential target for suppressing tumor metastasis.

Massive hyper-progression during anti-PD1 immunotherapy in a young patient with metastatic mucinous adenocarcinoma of the right colon: a case report and literature review

: Immune checkpoint inhibitors (ICIs) have dramatically changed the treatment landscape of both solid and hematological malignancies, including tumors historically considered “non-immunogenic”, such as colorectal cancer (CRC). The increasing use of immunotherapy brought to light novel patterns of response due to its intrinsic mechanism of action. Besides the “pseudo-progression”, another peculiar phenomenon linked to ICIs activity is the “hyper-progression” (HP), namely a paradoxical disease acceleration during immunotherapy. This event, which suggests potentially deleterious effects of immunotherapy, has not been yet completely understood and lacks strict definition criteria, pathogenetic characterization as well as predictive factors. In this report, we present a case of an atypical massive progression in a 40-years old man with metastatic mucinous right colon cancer harboring high microsatellites instability (MSI-H), occurring after 2 cycles of pembrolizumab as first line therapy. Unfortunately, he experienced a widespread cancer dissemination for massive bone colonization and both numerical and volumetric increase of pre-existing node metastasis associated with rapid clinical worsening, which were suggestive for HP. To our knowledge, this is one of the few cases of HP in metastatic CRC that has been reported, particularly with a so rapid clinical deterioration and massive skeletal involvement. Other experiences and further studies are warranted to better understand this phenomenon and anticipate its recognition.