Microcystic Adnexal Carcinoma. A Rare Entity.

Background: Microcystic adnexal carcinoma is a rare malignant tumour derived from sweat glands, locally aggressive, but with low rate of lymphatic or metastatic spread. Tends to affect the deep dermis, without affection of epidermis. Surgery remains as the first line treatment. Case Report: We present a case of a 46-year-old woman with a slow growing lesion of the upper lip, with biopsy diagnosis of microcystic adnexal carcinoma. She underwent a resection and reconstruction with local advancement flaps. The final anatomopathological study showed an adnexal epithelial neoplasm with imprecise borders, poorly delimited, non-encapsulated, growing in plaque-like formation from the superficial dermis into the adipose tissue, perineural invasion, without epidermal infiltration. Discussion: It is an extremely rare malignant tumour, appearing as a solitary papule or plaque affecting the central face, that often affect middle-aged caucasic, female patients. Usual local aggressive nature, characterized by small nests and strands of cells in deep dermis and perineural-invasion images, absent in superficial tissue. An incisional biopsy is need to make a correct diagnosis. Due to its rarity there is no consensus on the best management and follow-up. The microcystic adnexal carcinoma should be taken into consideration in the differential diagnosis. Key words:Microcystic adnexal carcinoma, lip, histopathology.

Characterizing language production across modalities.

ABSTRACTThis study investigates factors influencing lexical access in language production across modalities (signed and oral). Data from deaf and hearing signers were reanalyzed (Baus and Costa, 2015, On the temporal dynamics of sign production: An ERP study in Catalan Sign Language (LSC). Brain Research, 1609(1), 40-53. https://doi.org/10.1016/j.brainres.2015.03.013; Gimeno-Martínez and Baus, 2022, Iconicity in sign language production: Task matters. Neuropsychologia, 167, 108166. https://doi.org/10.1016/j.neuropsychologia.2022.108166) testing the influence of psycholinguistic variables and ERP mean amplitudes on signing and naming latencies. Deaf signers' signing latencies were influenced by sign iconicity in the picture signing task, and by spoken psycholinguistic variables in the word-to-sign translation task. Additionally, ERP amplitudes before response influenced signing but not translation latencies. Hearing signers' latencies, both signing and naming, were influenced by sign iconicity and word frequency, with early ERP amplitudes predicting only naming latencies. These findings highlight general and modality-specific determinants of lexical access in language production.

The hepatokine FGL1 regulates hepcidin and iron metabolism during anemia in mice by antagonizing BMP signaling.

ABSTRACT: As a functional component of erythrocyte hemoglobin, iron is essential for oxygen delivery to all tissues in the body. The liver-derived peptide hepcidin is the master regulator of iron homeostasis. During anemia, the erythroid hormone erythroferrone regulates hepcidin synthesis to ensure the adequate supply of iron to the bone marrow for red blood cell production. However, mounting evidence suggested that another factor may exert a similar function. We identified the hepatokine fibrinogen-like 1 (FGL1) as a previously undescribed suppressor of hepcidin that is induced in the liver in response to hypoxia during the recovery from anemia, and in thalassemic mice. We demonstrated that FGL1 is a potent suppressor of hepcidin in vitro and in vivo. Deletion of Fgl1 in mice results in higher hepcidin levels at baseline and after bleeding. FGL1 exerts its activity by directly binding to bone morphogenetic protein 6 (BMP6), thereby inhibiting the canonical BMP-SMAD signaling cascade that controls hepcidin transcription.

Enhanced SREBP2-driven cholesterol biosynthesis by PKCλ/ι deficiency in intestinal epithelial cells promotes aggressive serrated tumorigenesis.

The metabolic and signaling pathways regulating aggressive mesenchymal colorectal cancer (CRC) initiation and progression through the serrated route are largely unknown. Although relatively well characterized as BRAF mutant cancers, their poor response to current targeted therapy, difficult preneoplastic detection, and challenging endoscopic resection make the identification of their metabolic requirements a priority. Here, we demonstrate that the phosphorylation of SCAP by the atypical PKC (aPKC), PKCλ/ι promotes its degradation and inhibits the processing and activation of SREBP2, the master regulator of cholesterol biosynthesis. We show that the upregulation of SREBP2 and cholesterol by reduced aPKC levels is essential for controlling metaplasia and generating the most aggressive cell subpopulation in serrated tumors in mice and humans. Since these alterations are also detected prior to neoplastic transformation, together with the sensitivity of these tumors to cholesterol metabolism inhibitors, our data indicate that targeting cholesterol biosynthesis is a potential mechanism for serrated chemoprevention.

Iron chelation improves ineffective erythropoiesis and iron overload in myelodysplastic syndrome mice.

Myelodysplastic syndrome (MDS) is a heterogeneous group of bone marrow stem cell disorders characterized by ineffective hematopoiesis and cytopenias, most commonly anemia. Red cell transfusion therapy for anemia in MDS results in iron overload, correlating with reduced overall survival. Whether the treatment of iron overload benefits MDS patients remains controversial. We evaluate underlying iron-related pathophysiology and the effect of iron chelation using deferiprone on erythropoiesis in NUP98-HOXD13 transgenic mice, a highly penetrant well-established MDS mouse model. Our results characterize an iron overload phenotype with aberrant erythropoiesis in these mice which was reversed by deferiprone-treatment. Serum erythropoietin levels decreased while erythroblast erythropoietin receptor expression increased in deferiprone-treated MDS mice. We demonstrate, for the first time, normalized expression of the iron chaperones Pcbp1 and Ncoa4 and increased ferritin stores in late-stage erythroblasts from deferiprone-treated MDS mice, evidence of aberrant iron trafficking in MDS erythroblasts. Importantly, erythroblast ferritin is increased in response to deferiprone, correlating with decreased erythroblast ROS. Finally, we confirmed increased expression of genes involved in iron uptake, sensing, and trafficking in stem and progenitor cells from MDS patients. Taken together, our findings provide evidence that erythroblast-specific iron metabolism is a novel potential therapeutic target to reverse ineffective erythropoiesis in MDS.

High Influenza Incidence and Disease Severity Among Children and Adolescents Aged <18 Years - United States, 2022-23 Season.

During the 2022-23 influenza season, early increases in influenza activity, co-circulation of influenza with other respiratory viruses, and high influenza-associated hospitalization rates, particularly among children and adolescents, were observed. This report describes the 2022-23 influenza season among children and adolescents aged <18 years, including the seasonal severity assessment; estimates of U.S. influenza-associated medical visits, hospitalizations, and deaths; and characteristics of influenza-associated hospitalizations. The 2022-23 influenza season had high severity among children and adolescents compared with thresholds based on previous seasons' influenza-associated outpatient visits, hospitalization rates, and deaths. Nationally, the incidences of influenza-associated outpatient visits and hospitalization for the 2022-23 season were similar for children aged <5 years and higher for children and adolescents aged 5-17 years compared with previous seasons. Peak influenza-associated outpatient and hospitalization activity occurred in late November and early December. Among children and adolescents hospitalized with influenza during the 2022-23 season in hospitals participating in the Influenza Hospitalization Surveillance Network, a lower proportion were vaccinated (18.3%) compared with previous seasons (35.8%-41.8%). Early influenza circulation, before many children and adolescents had been vaccinated, might have contributed to the high hospitalization rates during the 2022-23 season. Among symptomatic hospitalized patients, receipt of influenza antiviral treatment (64.9%) was lower than during pre-COVID-19 pandemic seasons (80.8%-87.1%). CDC recommends that all persons aged ≥6 months without contraindications should receive the annual influenza vaccine, ideally by the end of October.

The hepatokine FGL1 regulates hepcidin and iron metabolism during the recovery from hemorrhage-induced anemia in mice.

As a functional component of erythrocyte hemoglobin, iron is essential for oxygen delivery to all tissues in the body. The liver-derived peptide hepcidin is the master regulator of iron homeostasis. During anemia, the erythroid hormone erythroferrone regulates hepcidin synthesis to ensure adequate supply of iron to the bone marrow for red blood cells production. However, mounting evidence suggested that another factor may exert a similar function. We identified the hepatokine FGL1 as a previously undescribed suppressor of hepcidin that is induced in the liver in response to hypoxia during the recovery from anemia and in thalassemic mice. We demonstrated that FGL1 is a potent suppressor of hepcidin in vitro and in vivo . Deletion of Fgl1 in mice results in a blunted repression of hepcidin after bleeding. FGL1 exerts its activity by direct binding to BMP6, thereby inhibiting the canonical BMP-SMAD signaling cascade that controls hepcidin transcription. Key points: 1/ FGL1 regulates iron metabolism during the recovery from anemia. 2/ FGL1 is an antagonist of the BMP/SMAD signaling pathway.

Survival rate of odontogenic descending necrotizing mediastinitis. Our experience in last 5 years

Background: Descending necrotising mediastinitis is one of the most lethal and least frequent forms of mediastinitis. It is a life-threatening infection most frequently originating from an oropharyngeal or odontogenic infection.Material and methods: A retrospective study of 6 patients diagnosed and treated for descending necrotising mediastinitis between 2015 and 2020 is reported.Results: All patients were male, mean age of 34.83 years; 66% were smokers. 83% had an orocervical infection and 34% had initial mediastinal spread. All patients were treated initially with empirical broad-spectrum antibiotics and surgical drainage, with subsequent admission to the Intensive Care Unit; only one of them required tracheostomy. The mean hospital stay was 27.37 days. After a mean follow-up of 6 months, 100% of the cases had a complete recovery.Conclusions: Early diagnosis and surgical treatment combined with improved life-support treatment in intensive care units and broad-spectrum antibiotic therapy leads to a decrease in associated mortality. (AU)

Hyaluronan driven by epithelial aPKC deficiency remodels the microenvironment and creates a vulnerability in mesenchymal colorectal cancer.

Mesenchymal colorectal cancer (mCRC) is microsatellite stable (MSS), highly desmoplastic, with CD8+ T cells excluded to the stromal periphery, resistant to immunotherapy, and driven by low levels of the atypical protein kinase Cs (aPKCs) in the intestinal epithelium. We show here that a salient feature of these tumors is the accumulation of hyaluronan (HA) which, along with reduced aPKC levels, predicts poor survival. HA promotes epithelial heterogeneity and the emergence of a tumor fetal metaplastic cell (TFMC) population endowed with invasive cancer features through a network of interactions with activated fibroblasts. TFMCs are sensitive to HA deposition, and their metaplastic markers have prognostic value. We demonstrate that in vivo HA degradation with a clinical dose of hyaluronidase impairs mCRC tumorigenesis and liver metastasis and enables immune checkpoint blockade therapy by promoting the recruitment of B and CD8+ T cells, including a proportion with resident memory features, and by blocking immunosuppression.

Assessment of Quality of Life in Head-and-Neck Oncologic Patients with Intraoral Soft-Tissue Defects Reconstructed with Buccinator Myomucosal Flap.

The aim of this study is to evaluate the functional outcomes and quality of life (QoL) in oncologic patients with intraoral defects reconstructed with the buccinator myomucosal flap. A retrospective study was performed involving 39 patients with intraoral soft-tissue defects, reconstructed with a buccinator myomucosal flap during a six-year period. Patients completed the European Organization for Research and Treatment of Cancer questionnaires, the standard questionnaire (QLQ-C30) and the head-and-neck specific module (QLQ-H&N35). Thirty-nine patients with a mean age of 61.23 ± 15.80 years were included in the study. Thirty-three patients were diagnosed with an oncological condition (84.61%). Six patients (15.38%) developed orosinusal communication and underwent extensive debridement. The median global-health-status score was 79.27 and emotional performance was the lowest scoring, with a mean score of 76.93. As for the symptom items, the most outstanding were dental problems (33.33), oral opening (31.62) and dry mouth (37.61), followed by sticky saliva (24.79), problems with social eating (21.15) and pain (19.87). The most significant symptoms were radiotherapy-related adverse effects such as pain, fatigue, dental problems and dry mouth. Patients reconstructed with the buccinator myomucosal flap develop a good quality of life for all types of activities, and a correct function and aesthetics. Postoperative radiotherapy is associated with a poorer quality of life, and can lead to impairment of several symptoms such as swallowing, oral opening and dry mouth.

The Complete Genome Sequence of Amorphophallus titanum, the Corpse Flower.

The Corpse Flower, or Titan Arum (Amorphophallus titanum) is a flowering plant in the family Araceae. endemic to a limited range in the rainforests of Sumatra, Indonesia. It is notable for two reasons: it produces the world's largest known unbranched flower, and it produces a strong odor of rotting meat to attract pollinators. We present the whole genome sequence of this species. A total of 335,712,220 paired-end Illumina reads consisting of 100.7G bases were obtained by Illumina sequencing the leaf tissue of a single individual. The reads were assembled by a de novo method followed by contig extension using related species as references. The raw and assembled data is publicly available via Genbank: Sequence Read Archive (SRR11565159) and genome assembly (GCA_024336825).

Iconicity in sign language production: Task matters.

The present study explored the influence of iconicity on sign lexical retrieval and whether it is modulated by the task at hand. Lexical frequency was also manipulated to have an index of lexical processing during sign production. Behavioural and electrophysiological measures (ERPs) were collected from 22 Deaf bimodal bilinguals while performing a picture naming task in Catalan Sign Language (Llengua de Signes Catalana, LSC) and a word-to-sign translation task (Spanish written-words to LSC). Iconicity effects were observed in the picture naming task, but not in the word-to-sign translation task, both behaviourally and at the ERP level. In contrast, frequency effects were observed in the two tasks, with ERP effects appearing earlier in the word-to-sign translation than in the picture naming task. These results support the idea that iconicity in sign language is not pervasive but modulated by task demands. As discussed, iconicity effects in sign language would be emphasised when naming pictures because sign lexical representations in this task are retrieved via semantic-to-phonological links. Conversely, attenuated iconicity effects when translating words might result from sign lexical representations being directly accessed from the lexical representations of the word.

Rumination Syndrome in Children and Adolescents: A Mini Review.

Introduction: Rumination syndrome involves recurrent regurgitation of food and is believed to be underdiagnosed with patients experiencing long delays in diagnosis. It can be associated with significant social consequences, high rates of school absenteeism, and medical complications such as weight loss. The primary aims of the current review are to assess the literature regarding prevalence, pathophysiology, and treatment outcomes with a focus on neurotypical children and adolescents. Results: Population studies in children/adolescents, 5 years of age or older, range from 0 to 5.1%. There are fewer studies in clinical settings, but the prevalence appears to be higher in patients with other gastrointestinal symptoms, particularly chronic vomiting. While physiologic changes that occur during a rumination episode are well-described, the underlying cause is less well-defined. In general, rumination appears to have similarities to other functional gastrointestinal disorders including dysmotility, possibly inflammation, and an interaction with psychologic function. While diaphragmatic breathing is considered the mainstay of treatment, pediatric data demonstrating efficacy is lacking, especially as an isolated treatment. Conclusion: Pediatric rumination syndrome remains greatly understudied, particularly regarding treatment. There is a need to better define prevalence in both the primary care and subspecialty clinical settings, especially in patients presenting with vomiting or apparent gastroesophageal reflux. There is a need to determine whether treatment of co-morbid conditions results in improvement of rumination. Diaphragmatic breathing needs to be studied and compared to other competing responses.

Functional Outcomes with Facial Artery Musculo-Mucosal (FAMM) Flap and Dental Implants for Reconstruction of Floor of the Mouth and Tongue Defects in Oncologic Patients.

Optimal functional outcomes in oncologic patients with squamous cell carcinoma (SCCA) of the tongue and floor of the mouth require good lingual mobility, adequate facial competence, the cheek suction effect and dental rehabilitation with osseointegrated implants. In this study, twenty-two oncologic patients who had been diagnosed with intraoral SCCA affecting the tongue and the floor of the mouth and who had undergone wide resection of the tumor and immediate reconstruction with an inferiorly pedicled FAMM flap and immediate osseointegrated implants were assessed. Lingual mobility, speech articulation, deglutition, implant success rate, mouth opening, and aesthetic results were evaluated. All patients were staged as T2 and the defect size ranged from 3.7 × 2.1 cm to 6.3 × 4.2 cm. A selective neck dissection was performed in all patients as part of their oncologic treatment, either electively or for node positive disease. Thirteen patients (59%) were diagnosed with node positive disease and underwent adjuvant radiotherapy. A total of 101 osseointegrated implants were placed for prosthetic rehabilitation and 8 implants were lost (7.9%), of which 7 received radiotherapy (87.5%). The implant success rate was 92.1%. Mouth opening was reported as normal in 19 patients (86.3%). Tongue tip elevation was reported as excellent in 19 patients (86.3%) and good in 3 patients (13.6%). Lingual protrusion was referred to as excellent in 15 patients (68.2%) and good in 6 patients (27.2%). Lateral excursion was reported as excellent in 14 patients (63.6%) and good in 7 patients (31.8%). In terms of speech articulation, 20 patients reported normal speech (90.9%). Regarding deglutition, 19 patients (86.3%) reported a regular diet while a soft diet was reported by 3 patients (13.7%). Aesthetic results were referred to as excellent in 17 patients (77.3%). FAMM flaps, immediate implants and fixed prostheses enable the functional rehabilitation of oncologic patients, optimizing aesthetics and functional outcomes even in patients undergoing irradiation, thus returning oncologic patients to an excellent quality of life.

Pleckstrin-2 is essential for erythropoiesis in ß-thalassemic mice, reducing apoptosis and enhancing enucleation.

Erythropoiesis involves complex interrelated molecular signals influencing cell survival, differentiation, and enucleation. Diseases associated with ineffective erythropoiesis, such as ß-thalassemias, exhibit erythroid expansion and defective enucleation. Clear mechanistic determinants of what make erythropoiesis effective are lacking. We previously demonstrated that exogenous transferrin ameliorates ineffective erythropoiesis in ß-thalassemic mice. In the current work, we utilize transferrin treatment to elucidate a molecular signature of ineffective erythropoiesis in ß-thalassemia. We hypothesize that compensatory mechanisms are required in ß-thalassemic erythropoiesis to prevent apoptosis and enhance enucleation. We identify pleckstrin-2-a STAT5-dependent lipid binding protein downstream of erythropoietin-as an important regulatory node. We demonstrate that partial loss of pleckstrin-2 leads to worsening ineffective erythropoiesis and pleckstrin-2 knockout leads to embryonic lethality in ß-thalassemic mice. In addition, the membrane-associated active form of pleckstrin-2 occurs at an earlier stage during ß-thalassemic erythropoiesis. Furthermore, membrane-associated activated pleckstrin-2 decreases cofilin mitochondrial localization in ß-thalassemic erythroblasts and pleckstrin-2 knockdown in vitro induces cofilin-mediated apoptosis in ß-thalassemic erythroblasts. Lastly, pleckstrin-2 enhances enucleation by interacting with and activating RacGTPases in ß-thalassemic erythroblasts. This data elucidates the important compensatory role of pleckstrin-2 in ß-thalassemia and provides support for the development of targeted therapeutics in diseases of ineffective erythropoiesis.

The hepcidin regulator erythroferrone is a new member of the erythropoiesis-iron-bone circuitry.

Background: Erythroblast erythroferrone (ERFE) secretion inhibits hepcidin expression by sequestering several bone morphogenetic protein (BMP) family members to increase iron availability for erythropoiesis. Methods: To address whether ERFE functions also in bone and whether the mechanism of ERFE action in bone involves BMPs, we utilize the Erfe-/- mouse model as well as ß-thalassemic (Hbbth3/+) mice with systemic loss of ERFE expression. In additional, we employ comprehensive skeletal phenotyping analyses as well as functional assays in vitro to address mechanistically the function of ERFE in bone. Results: We report that ERFE expression in osteoblasts is higher compared with erythroblasts, is independent of erythropoietin, and functional in suppressing hepatocyte hepcidin expression. Erfe-/- mice display low-bone-mass arising from increased bone resorption despite a concomitant increase in bone formation. Consistently, Erfe-/- osteoblasts exhibit enhanced mineralization, Sost and Rankl expression, and BMP-mediated signaling ex vivo. The ERFE effect on osteoclasts is mediated through increased osteoblastic RANKL and sclerostin expression, increasing osteoclastogenesis in Erfe-/- mice. Importantly, Erfe loss in Hbbth3/+mice, a disease model with increased ERFE expression, triggers profound osteoclastic bone resorption and bone loss. Conclusions: Together, ERFE exerts an osteoprotective effect by modulating BMP signaling in osteoblasts, decreasing RANKL production to limit osteoclastogenesis, and prevents excessive bone loss during expanded erythropoiesis in ß-thalassemia. Funding: YZG acknowledges the support of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (R01 DK107670 to YZG and DK095112 to RF, SR, and YZG). MZ acknowledges the support of the National Institute on Aging (U19 AG60917) and NIDDK (R01 DK113627). TY acknowledges the support of the National Institute on Aging (R01 AG71870). SR acknowledges the support of NIDDK (R01 DK090554) and Commonwealth Universal Research Enhancement (CURE) Program Pennsylvania.

Secondary Cervicofacial Soft Tissue Reconstruction With Upper Trapezius Myocutaneous Flap in "Frozen Neck" With Bone Flap and Reconstructive Plate Exposure.

ABSTRACT: A frozen neck is a scarred neck with severe fibrosis with a loss of tissue planes secondary to prior irradiation with or without surgery. The purpose of this study was to evaluate the outcomes of cervicofacial reconstruction in patients with soft tissue defects and bone flap and reconstruction plate exposure with the upper trapezius myocutaneous flap. Fifteen oncologic patients with prior surgery and radiotherapy developed soft tissue dehiscence with bone and osteosynthesis material exposure. All patients had either a frozen neck or a vessel-depleted neck. The soft tissue defects were reconstructed, the osteosynthesis material was removed and the bone flap exposure was covered in all patients. One patient developed a seroma and 1 patient reported wound dehiscence. In terms of esthetic results, 6 patients referred a good esthetic result, whereas 8 patients referred a fair result and 1 patient a poor result. Two patients with prior radical neck dissection reported a poor functional result in the ipsilateral shoulder, previously to secondary reconstruction. Functional neck dissection was performed in 10 patients, 8 patients referred a good functional outcome and 2 patients reported a fair result. The upper trapezius flap is an extremely reliable source for secondary cervicofacial soft tissue reconstruction in "frozen neck." In comparison with other locoregional flaps, the upper trapezius flap fulfills all aesthetic and functional criteria for secondary cervicofacial soft tissue reconstruction.

Influence of Gesture and Linguistic Experience on Sign Perception.

In the past years, there has been a significant increase in the number of people learning sign languages. For hearing second language (L2) signers, acquiring a sign language involves acquiring a new language in a different modality. Exploring how L2 sign perception is accomplished and how newly learned categories are created is the aim of the present study. In particular, we investigated handshape perception by means of two tasks, identification and discrimination. In two experiments, we compared groups of hearing L2 signers and groups with different knowledge of sign language. Experiment 1 explored three groups of children-hearing L2 signers, deaf signers, and hearing nonsigners. All groups obtained similar results in both identification and discrimination tasks regardless of sign language experience. In Experiment 2, two groups of adults-Catalan sign language learners (LSC) and nonsigners-perceived handshapes that could be permissible (either as a sign or as a gesture) or not. Both groups obtained similar results in both tasks and performed significantly different perceiving handshapes depending on their permissibility. The results obtained here suggest that sign language experience is not a determinant factor in handshape perception and support other hypotheses considering gesture experience.

YKT6 expression, exosome release, and survival in non-small cell lung cancer.

BACKGROUND: Cancer-derived exosomes are involved in metastasis. YKT6 is a SNARE protein that participates in the regulation of exosome production and release, but its role in non-small cell lung cancer (NSCLC) has not been examined. MATERIALS AND METHODS: Ultracentrifugation-purified exosomes from the A549 cell line were studied by CRYO-TEM, nanoparticle tracking analysis and western blot (TSG101 marker). YKT6 was inhibited using a DsiRNA and selected pre-microRNAs. MicroRNAs targeting YKT6 were validated by Renilla/Luciferase assay and western blot. YKT6 expression and its prognostic impact were analyzed in 98 tissue specimens from resected NSCLC patients. RESULTS: Membranous nanosized vesicles (mode size: 128nm) with TSG101 protein were purified from A549 cells. YKT6 inhibition reduced exosome release by 80.9%. We validated miR-134 and miR-135b as miRNAs targeting YKT6, and transfection with the pre-miRNAs also produced a significant reduction in exosome release. The analysis of YKT6 in tumor samples showed that patients with high levels had shorter disease-free and overall survival. CONCLUSIONS: YKT6 is a key molecule in the regulation of exosome release in lung cancer cells and is in turn precisely regulated by miR-134 and miR-135b. Moreover, YKT6 levels impact prognosis of resected NSCLC patients.

Identifying High-Risk Stage II Colon Cancer Patients: A Three-MicroRNA-Based Score as a Prognostic Biomarker.

BACKGROUND: The potential benefit of adjuvant chemotherapy in surgically resected patients with stage II colorectal cancer is controversial. The current guidelines, which are based solely on clinical factors, have limited usefulness, and a clear need exists for biomarkers to supplement the clinical information. MicroRNAs (miRNAs) have previously been shown to be useful cancer biomarkers. In the present study, we assessed the usefulness of a miRNA score to help identify the subset of high-risk patients likely to benefit from adjuvant chemotherapy. PATIENTS AND METHODS: Six miRNAs previously identified as prognostic markers in Asian patients (miR-21-5p, miR-20a-5p, miR-103a-3p, miR-106b-5p, miR-143-5p, and miR-215) were studied in tumor samples from 71 white patients with stage II colon cancer. RESULTS: Three miRNAs (miR-103a-3p, miR-143-5p, and miR-215) emerged as independent prognostic markers on multivariate analysis and were used to construct a miRNA-based score that classified patients into high- and low-risk groups. The patients in the high-risk group had significantly shorter disease-free survival compared with their low-risk counterparts (P = .003). The time-dependent receiver operating characteristic curve analysis showed that our 3-miRNA score improved the prediction of outcome when added to the clinical features (P = .023). CONCLUSION: Our 3-miRNA score added valuable prognostic information to the clinical features in stage II colon cancer. Further research in this field could provide useful tools to determine whether adjuvant chemotherapy would benefit patients with stage II colon cancer after surgery.