RESUMO
PURPOSE: To identify genes associated with treatment response and prognosis for locally advanced rectal cancer (LARC) patients receiving neoadjuvant chemoradiotherapy (NCRT). METHODS: In our cohort, gene expression profiles of 64 tumor biopsy samples before NCRT were examined and generated. Weighted gene co-expression network analysis was performed to identify gene modules. External validation datasets included GSE3493, GSE119409, and GSE133057. The expression of candidate genes was evaluated using immunohistochemistry (IHC). TIMER was used to assess immune infiltration. RESULTS: We identified and validated the capability to predict the treatment response of CCT5 and ELF1 using our data and external validation datasets. The trends of survival differences of candidate genes in the GSE133057 dataset were similar to our cohort. High levels of CCT5 and ELF1 expression were associated with NCRT resistance and poor prognosis. Furthermore, the expression of CCT5 and ELF1 were also assessed in 117 LARC patients' samples by the IHC method. Based on IHC results and Cox analysis, the risk score model with CCT5 and ELF1 was constructed and performed well. The risk score was an independent prognostic factor for progression-free survival and overall survival in LARC patients and was then used to build nomogram models. The underlying mechanisms of CCT5 and ELF1 were explored using gene set enrichment analysis. The underlying pathway including apoptosis, cell cycle, and other processes. CCT5 and ELF1 expressions were significantly correlated with immune cell infiltration. CONCLUSION: CCT5 and ELF1 were determined as biomarkers for treatment response and prognosis in LARC patients. The risk score model and nomograms helped predict treatment response and survival outcomes for LARC patients undergoing NCRT.
Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Humanos , Terapia Neoadjuvante/métodos , Quimiorradioterapia/métodos , Neoplasias Retais/genética , Neoplasias Retais/terapia , Prognóstico , BiomarcadoresRESUMO
BACKGROUND: Gastrointestinal stromal tumor (GIST) is currently regarded as a potentially malignant tumor, and early diagnosis is the best way to improve its prognosis. Therefore, it will be meaningful to develop a new method for auxiliary diagnosis of this disease. METHODS: Here we try out a new means to detect GIST by combining two-photon imaging with automatic image processing strategy. RESULTS: Experimental results show that two-photon microscopy has the ability to label-freely identify the structural characteristics of GIST such as tumor cells, desmoplastic reaction, which are entirely different from those from gastric adenocarcinoma. Moreover, an image processing approach is used to extract eight collagen morphological features from tumor microenvironment and normal muscularis, and statistical analysis demonstrates that there are significant differences in three features-fiber area, density and cross-link density. The three morphological characteristics may be considered as optical imaging biomarkers to differentiate between normal and abnormal tissues. CONCLUSION: With continued improvement and refinement of this technology, we believe that two-photon microscopy will be an efficient surveillance tool for GIST and lead to better management of this disease.
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Tumores do Estroma Gastrointestinal , Neoplasias Gástricas , Humanos , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/patologia , Microscopia , Neoplasias Gástricas/patologia , Prognóstico , Colágeno , Microambiente TumoralRESUMO
BACKGROUND: No studies have investigated the role of IPI in assessing the prognosis of locally advanced rectal cancer (LARC) patients undergoing nCRT. OBJECTIVE: We attempted to combine neutrophil-to-lymphocyte ratio (NLR) and serum lactate dehydrogenase (sLDH) to generate a new rectal immune prognostic index (RIPI) to explore whether RIPI is associated with LARC prognosis. We aimed to identify whether there is a population that might benefit from RIPI in LARC. METHODS: LARC patients who underwent radical surgery after Neoadjuvant chemoradiotherapy (nCRT) were enrolled between February 2012 and May 2017. Based on the best cut-off points of NLR and sLDH, we developed RIPI. The patients were grouped as follows: (1) good, RIPI = 0, good, 0 factors; (2) poor, RIPI = 1, 1 or 2 factors. RESULTS: This study enrolled 642 patients. In yp TNM stage II patients, 5-year disease-free survival (DFS) differed significantly between the RIPI = 1 and RIPI = 0 groups (p = 0.03). Five-year DFS did not differ significantly between IPI = 0 and IPI = 1 groups in ypCR, stage I, stage II, and stage III. In multivariate analysis, the significant factor predicting DFS was pre-nCRT RIPI score (p = 0.035). CONCLUSION: The pre-nCRT RIPI was closely related to the prognosis of LARC patients undergoing nCRT. Particularly, RIPI is significant in evaluating the prognosis of ypTNM stage II LARC patients who underwent radical resection after nCRT.
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Terapia Neoadjuvante , Neoplasias Retais , Humanos , Prognóstico , Quimiorradioterapia , Estudos Retrospectivos , Neoplasias Retais/terapiaRESUMO
BACKGROUND: The operative results of different approaches for the laparoscopic intersphincteric resection (LAISR) of low rectal cancer vary, and the patient characteristics associated with the best outcomes for each procedure have not been reported. We compared the efficacy of different approaches for LAISR of low rectal cancer and discussed the surgical indications for each approach. METHODS: We retrospectively reviewed data from 235 patients with low rectal cancer treated via LAISR from October 2010 to September 2016. Patients underwent either the transabdominal approach for ISR (TAISR, n = 142), the transabdominal perineal approach for ISR (TPAISR, n = 57), or the transanal pull-through approach for ISR (PAISR, n = 36). RESULTS: The PAISR and TAISR groups exhibited shorter operation times and less intraoperative blood loss than the TPAISR group. The anastomotic distance was shorter in the PAISR and TPAISR groups than in the TAISR group. No differences in the ability to perform radical resection, overall complications, postoperative recovery, Wexner score recorded 12 months after ostomy closure, 3-year disease-free survival, local recurrence-free survival, distant metastasis-free survival, or overall survival (OS) were observed among the three groups. CONCLUSIONS: TAISR, TPAISR, and PAISR have unique advantages and do not differ in terms of operation safety, patient outcomes, or anal function. TPAISR requires a longer time to complete and is associated with more bleeding and a slower recovery of anal function. PAISR should be considered when TAISR cannot ensure a negative distal margin and the tumor and BMI are relatively small; otherwise, TPAISR is required.
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Laparoscopia , Neoplasias Retais , Canal Anal/patologia , Canal Anal/cirurgia , Humanos , Laparoscopia/métodos , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: To develop and evaluate the prognostic value of a comprehensive inflammatory biomarker for postoperative colorectal cancer (CRC) patients. METHODS: A total of 646 CRC patients were recruited between August 2017 and December 2019 from Fujian Medical University Union Hospital, with follow-up data up to 2021. The least absolute shrinkage and selection operator method (LASSO) was used to select inflammation indicators in order to construct a comprehensive biomarker (named NSAP). The Cox regression model was utilized to analyze the association between the NSAP and the disease-free survival (DFS) of CRC. Predictive performance and clinical utility of prognostic models were evaluated by area under the curve (AUC) and decision curve analyses (DCAs). RESULTS: During a median follow-up of 23 months, 95 clinical outcomes were observed, with a 1-year survival rate is 89.47%. A comprehensive inflammatory biomarker (NSAP) was established based on four blood indicators (including neutrophil-to-lymphocyte ratio (NLR), neutrophil×monocyte-to-lymphocyte ratio (SIRI), albumin-to-globulin ratio (AGR), and platelet-to-lymphocytes ratio (PLR)). Patients with a lower NSAP had significantly associated with better DFS of CRC (HR=0.53, 95%CI 0.32-0.89). Moreover, compared to a previously established model, the traditional TNM staging system or/and tumor markers, the nomogram based on NSAP displayed more excellent predictive ability (0.752 vs 0.597, 0.711 and 0.735, P < 0.05). DCAs also demonstrated that the established nomogram had better utility for decision making. CONCLUSIONS: Our study suggests that NSAP may be a useful comprehensive prognostic biomarker for predicting the DFS of CRC patients. The nomogram based on NSAP can be considered a valuable tool to estimate the prognosis of patients with CRC.
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Neoplasias Colorretais , Biomarcadores Tumorais , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Humanos , Inflamação , Contagem de Plaquetas , PrognósticoRESUMO
The aim of this study was to explore the role of sulfasalazine on proliferation and metastasis in gastric cancer by inhibition of xCT. The relationships between clinical characteristics and xCT expression were analysed. An immunohistochemical staining assay and Western blot were performed among gastric cancers and normal gastric tissues. qPCR and Western blot were also used to evaluate the mRNA and protein expression in the normal gastric cell and eight gastric cancer cells, respectively. CCK-8 and colony formation assays were used to evaluate the effect of sulfasalazine on the proliferation and colony formation ability of three gastric cancers. The effect of sulfasalazine on the migration and invasion abilities of three cancer cells was assessed by the Transwell assay. xCT protein is up-regulated in gastric cancer specimens and cells. Three gastric cancer cells with high, medium and low expression of xCT were selected for the following analyses. CCK-8 assays revealed that sulfasalazine could attenuate the proliferation of HGC-27 and AGS. Also, the colony formation assay revealed that sulfasalazine might attenuate the colony formation ability in HGC-27 and AGS cells. Plus, the Transwell assays demonstrated that sulfasalazine might attenuate the migration and invasion abilities in HGC-27 and AGS cells. In conclusion, higher expression of xCT is associated with advanced tumour stage and poor overall survival of gastric cancer. Sulfasalazine can attenuate the proliferation, colony formation, metastasis and invasion of gastric cancer in vitro. Further study is required to validate our findings.
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Sistema y+ de Transporte de Aminoácidos/antagonistas & inibidores , Anti-Inflamatórios não Esteroides/farmacologia , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Sulfassalazina/farmacologia , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Humanos , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
Currently, due to the low quality of RNA caused by degradation or low abundance, the accuracy of gene expression measurements by transcriptome sequencing (RNA-seq) is very challenging for non-research-oriented clinical samples, majority of which are preserved in hospitals or tissue banks worldwide with complete pathological information and follow-up data. Molecular signatures consisting of several genes are rarely applied to such samples. To utilize these resources effectively, 45 stage II non-research-oriented samples which were formalin-fixed paraffin-embedded (FFPE) colorectal carcinoma samples (CRC) using RNA-seq have been analysed. Our results showed that although gene expression measurements were significantly affected, most cancer features, based on the relative expression orderings (REOs) of gene pairs, were well preserved. We then developed two REO-based signatures, which consisted of 136 gene pairs for early diagnosis of CRC, and 4500 gene pairs for predicting post-surgery relapse risk of stage II and III CRC. The performance of our signatures, which included hundreds or thousands of gene pairs, was more robust for non-research-oriented clinical samples, compared to that of two published concise REO-based signatures. In conclusion, REO-based signatures with relatively more gene pairs could be robustly applied to non-research-oriented CRC samples.
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Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Transcriptoma , Sequência de Bases , Biomarcadores Tumorais/genética , Neoplasias Colorretais/diagnóstico , Bases de Dados Genéticas , Diagnóstico Precoce , Humanos , Mapas de Interação de Proteínas , RNA/isolamento & purificação , Transcrição GênicaRESUMO
BACKGROUND: Immunotherapies targeting ligand-receptor interactions (LRIs) are advancing rapidly in the treatment of colorectal cancer (CRC), and LRIs also affect many aspects of CRC development. However, the pattern of LRIs in CRC and their effect on tumor microenvironment and clinical value are still unclear. METHODS: We delineated the pattern of LRIs in 55,539 single-cell RNA sequencing (scRNA-seq) samples from 29 patients with CRC and three bulk RNA-seq datasets containing data from 1411 CRC patients. Then the influence of tumor microenvironment, immunotherapy and prognosis of CRC patients were comprehensively investigated. RESULTS: We calculated the strength of 1893 ligand-receptor pairs between 25 cell types to reconstruct the spatial structure of CRC. We identified tumor subtypes based on LRIs, revealed the relationship between the subtypes and immunotherapy efficacy and explored the ligand-receptor pairs and specific targets affecting the abundance of tumor-infiltrating lymphocytes. Finally, a prognostic model based on ligand-receptor pairs was constructed and validated. CONCLUSION: Overall, through the comprehensive and in-depth investigation of the existing ligand-receptor pairs, this study provides new ideas for CRC subtype classification, a new risk screening tool for CRC patients, and potential ligand-receptor pair targets and pathways for CRC therapy.
Assuntos
Neoplasias Colorretais , Microambiente Tumoral , Neoplasias Colorretais/patologia , Humanos , Ligantes , Linfócitos do Interstício Tumoral/metabolismo , Prognóstico , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: The well-differentiated rectal neuroendocrine tumors (RNETs) can also have lymph node metastasis (LNM). Large multicenter data were reviewed to explore the risk factors for LNM in RNETs. Further, we developed a model to predict the risk of LNM in RNETs. METHODS: In total, 223 patients with RNETs from the Fujian Medical University Union Hospital, the First Affiliated Hospital of Fujian Medical University, and the First Affiliated Hospital of Xiamen University were retrospectively enrolled. Logistic regression analysis was performed to study the factors affecting LNM, and recursive partitioning analysis (RPA) was performed to stratify the risk of LNM. RESULTS: Among the 223 patients diagnosed with RNETs, the incidence of LNM was 10.8%. Univariate and multivariate regression analyses revealed that tumor size, World Health Organization (WHO) grade, and depth of tumor invasion were independent risk factors for LNM (p < 0.05). The area under the curve was 0.948 (95% confidence interval: 0.890-1.000). Furthermore, the incidence of LNM in patients divided into low- and high-risk groups according to RPA was 1.1% and 56.4%, respectively. CONCLUSION: Compared with tumor size, the depth of tumor invasion and WHO grade are more important factors in predicting LNM. Then, we developed a model based on RPA to predict the risk of LNM in RNETs and identify patients who are suitable for local resection.
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Metástase Linfática , Tumores Neuroendócrinos/mortalidade , Neoplasias Retais/patologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Invasividade Neoplásica , Tumores Neuroendócrinos/patologia , Neoplasias Retais/mortalidade , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: D3 or complete mesocolic excision (CME) surgery has become a common surgical procedure for the treatment of colon cancer metastasis. Clinical misuse and overuse of lymph node dissection bring unnecessary burdens to patients. A detailed guidance for lymph node dissection in patients with T3 and T4 stage right colon cancer at different locations is urgently needed. METHODS: A retrospective study was performed. Patients received D3 or CME surgery were divided into ileocecal group, ascending colon group, and hepatic flexure group according to the 9th edition of the Japanese Society for Cancer of the Colon and Rectum guidelines. The distributions of lymph node metastases were analyzed according to tumor infiltration depth (T stage) and tumor location. RESULTS: The incidence of metastases in the paracolic area (or station), intermediate area, and main (or central) area was 38.4% (139/362), 12.7% (46/362), and 9.7% (35/362), respectively. The proportion of patients having No.206 and terminal ileum lymph nodes metastases was 7.7% (14/181) and 3.7% (9/244), respectively. No.206 lymph node metastasis is related to tumor location (χ2 = 7.955, p = 0.019) and degree of differentiation (χ2 = 18.99, p = 0.000), and terminal ileum lymph node metastasis is related to tumor location (χ2 = 6.273, p = 0.043). Patients with T3/T4 hepatic flexure cancer received radical right hemicolectomy in addition to No.206 lymph node dissection. CONCLUSION: Radical right hemicolectomy and No.206 group lymph node dissection are necessary for T3 and T4 stage colon cancer therapy.
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Neoplasias do Colo , Linfonodos , Neoplasias do Colo/cirurgia , Humanos , Íleo/cirurgia , Linfonodos/cirurgia , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: To evaluate the impact of age on the efficacy of neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced rectal cancer (LARC). METHOD: LARC patients undergoing NCRT and radical surgery from 2011 to 2018 were divided into young (< 40 years) and old (≥40 years) groups. Multivariate analyses were performed to identify predictive factors for pathological complete response (pCR). Predictive nomograms and decision curve analysis were used to compare the models including/excluding age groups. Immunohistochemical analysis was performed to detect CD133 expression in LARC patients. RESULT: A total of 901 LARC patients were analyzed. The young group was associated with poorly differentiated tumors, more metastatic lymph nodes, higher perineural invasion, and a lower tumor regression grade (P = 0.008; P < 0.001; P < 0.001; P = 0.003). Logistic regression analysis demonstrated that age < 40 years (HR = 2.190, P = 0.044), tumor size (HR = 0.538, P < 0.001), pre-NCRT cN stage (HR = 0.570, P = 0.036), and post-NCRT CEA level (HR = 0.877, P = 0.001) were significantly associated with pCR. Predictive nomograms and decision curve analysis demonstrated that the predictive ability of models including the age group was superior to that of models excluding the age group. Higher CD133 expression was more common in young LARC patients. CONCLUSION: Young patients with LARC were associated with lower pCR rates following NCRT. The ability of the predictive model was greater when based on the age group. Young LARC patients were associated with a higher CD133+ tumor stem cell burden, which contributed to the lower pCR rates.
Assuntos
Adenocarcinoma/terapia , Quimiorradioterapia/métodos , Terapia Neoadjuvante/métodos , Neoplasias Retais/terapia , Antígeno AC133/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/cirurgia , Adulto , Fatores Etários , Idoso , Terapia Combinada/métodos , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Nomogramas , Prognóstico , Estudos Prospectivos , Neoplasias Retais/metabolismo , Neoplasias Retais/cirurgia , Estudos RetrospectivosRESUMO
Currently, using biopsy specimens for the early diagnosis of colorectal cancer (CRC) is not entirely reliable due to insufficient sampling amount and inaccurate sampling location. Thus, it is necessary to develop a signature that can accurately identify patients with CRC under these clinical scenarios. Based on the relative expression orderings of genes within individual samples, we developed a qualitative transcriptional signature to discriminate CRC tissues, including CRC adjacent normal tissues from non-CRC individuals. The signature was validated using multiple microarray and RNA sequencing data from different sources. In the training data, a signature consisting of 7 gene pairs was identified. It was well validated in both biopsy and surgical resection specimens from multiple datasets measured by different platforms. For biopsy specimens, 97.6% of 42 CRC tissues and 94.5% of 163 non-CRC (normal or inflammatory bowel disease) tissues were correctly classified. For surgically resected specimens, 99.5% of 854 CRC tissues and 96.3% of 81 CRC adjacent normal tissues were correctly identified as CRC. Notably, we additionally measured 33 CRC biopsy specimens by the Affymetrix platform and 13 CRC surgical resection specimens, with different proportions of tumor epithelial cells, ranging from 40% to 100%, by the RNA sequencing platform, and all these samples were correctly identified as CRC. The signature can be used for the early diagnosis of CRC, which is also suitable for minimum biopsy specimens and inaccurately sampled specimens, and thus has potential value for clinical application.
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Biomarcadores Tumorais/genética , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Perfilação da Expressão Gênica/métodos , Biópsia , Estudos de Casos e Controles , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Sensibilidade e Especificidade , Análise de Sequência de RNA/métodosAssuntos
Laparoscopia , Neoplasias Retais , Humanos , Canal Anal , Dissecação , Neoplasias Retais/cirurgiaRESUMO
Neuroendocrine tumors (NETs), which are rare and slow-growing neoplasms, pose a diagnostic challenge as they are clinically silent at the time of presentation. Here, gastrointestinal neuroendocrine tumors were researched by nonlinear microscopy, and results demonstrate that this technique has the capability to identify neuroendocrine tumors in the absence of labels and can, in particular, detect rare neuroendocrine tumor cells, vascular invasion, desmoplastic reaction, and fibroelastosis induced by neuroendocrine tumors. These conclusions highlight the possibility of nonlinear optical microscopy as a diagnostic tool for label-freely differentiating neuroendocrine tumors by these histopathologic features.
Assuntos
Neoplasias Gastrointestinais/diagnóstico , Microscopia/métodos , Tumores Neuroendócrinos/diagnóstico , Neoplasias Gastrointestinais/diagnóstico por imagem , Humanos , Tumores Neuroendócrinos/diagnóstico por imagemRESUMO
BACKGROUND: Preoperative radiochemotherapy improves outcomes in patients with locally advanced rectal carcinoma, and has been used increasingly in patient management. However, there is a strong clinical need to assess tumor response to neoadjuvant treatment, and a non-invasive technique that allows the precise identification of morphologic changes in tumors would be of considerable clinical interest. METHODS: In this study, we used multiphoton microscopy (MPM) to detect morphologic alterations in rectal adenocarcinomas in patients treated with preoperative radiochemotherapy. RESULTS: MPM was able to identify histopathologic alterations in rectal cancer following preoperative radiochemotherapy, and allowed the qualitative assessment of treatment efficacy and feasibility in relation to dose or strategy. CONCLUSION: These findings may provide the groundwork for evaluating tumor response to neoadjuvant treatment, thus allowing the tailoring of effective treatment doses and strategies.
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Quimiorradioterapia/métodos , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Cuidados Pré-Operatórios/métodos , Neoplasias Retais/diagnóstico , Neoplasias Retais/terapia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
In this work, multiphoton microscopy (MPM), based on the nonlinear optical processes two-photon excited fluorescence (TPEF) and second harmonic generation (SHG), was extended to evaluate the feasibility of using MPM to distinguish layers of the bowel wall. It was found that MPM has the ability to identify the four-layer microstructures of colorectal tissues including mucosa, submucosa, muscularis propria, and serosa as there are many intrinsic signal sources in each layer. Our results also showed the capability of using the quantitative analyses of MPM images for quantifying some feature parameters including the nuclear area, nuclear-to-cytoplasmic ratio, and optical redox ratio. This work demonstrates that MPM has the potential in noninvasively monitoring the development and progression of colorectal diseases and then guiding effective treatment.
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Colo/patologia , Reto/patologia , Neoplasias Colorretais/diagnóstico , Humanos , Mucosa Intestinal/patologia , Microscopia de Fluorescência por Excitação MultifotônicaRESUMO
Background: Mucinous colonic adenocarcinoma remains a challenging disease due to its high propensity for metastasis and recurrence. N7-methylguanosine (m7G) and long non-coding RNA (lncRNA) are closely associated with the occurrence and progression of tumors. However, research on m7G-related lncRNA in mucinous colonic adenocarcinoma is lacking. Therefore, we sought to explore the prognostic impact of m7G-related lncRNAs in mucinous adenocarcinoma (MC) patients. Methods: In this study, Pearson analysis was used to identify m7G-related lncRNAs from transcriptome data in The Cancer Genome Atlas (TCGA). Univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression were used to further screen m7G-related lncRNAs and incorporate them into a prognostic signature. Based on the risk model, patients were divided into low- and high-risk groups and randomly assigned to the training set and test sets in a 6:4 ratio. Kaplan-Meier, receiver operating characteristic (ROC) curve, multivariate regression, and nomogram analyses were used to confirm the accuracy of the signature. The CIBERSORT algorithm was used to calculate the degree of immune cell infiltration (ICI). Finally, the correlation of the prognostic signature with tumor mutational burden (TMB) and immunophenotype score (IPS) was evaluated. Results: A total of 432 m7G-related lncRNAs were identified by Pearson analysis. Univariate Cox regression, LASSO regression and survival analysis were performed to further select six m7G-related lncRNAs (P<0.05): AC254629.1, LINC01133, LINC01134, MHENCR, SMIM2-AS1, and XACT. Based on the risk model, heat maps, Kaplan-Meier curves, and ROC curves were constructed, and the results showed that there were significant differences in expression levels and survival status between the two risk groups. The area under the ROC curve (AUC) values for 3-, 5-, and 10-year survival in the training set were 0.944, 0.957, and 1.000, respectively. And in the test set were 0.964, 1.000, and 1.000, respectively. Subsequently, univariate and multivariate regression analyses of clinical characteristics and risk score were performed. The results of risk score were [hazard ratio (HR): 6.458, 95% confidence interval (CI): 2.708-15.403, P<0.001; HR: 7.280, 95% CI: 2.500-21.203, P<0.001], respectively. Using the risk score as an independent prognostic factor, the AUC of it over 3, 5, and 10 years was 0.911, 0.955, and 0.961, respectively. Calibration plots for the nomogram show that the model calibration line is very close to the ideal calibration line, indicating good calibration. The level of ICI was significantly different in the different risk groups. Survival analysis showed that, regardless of TMB risk, patients with MC and a high-risk score consistently had a poor overall survival (OS). Conclusions: The m7G-related lncRNA prognostic signature has potential value for the prognosis of mucinous colonic adenocarcinoma.
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Microvascular invasion (MVI) is a critical risk factor for postoperative recurrence of hepatocellular carcinoma (HCC). This study aimed to firstly develop and validate nomograms based on MVI grade for predicting recurrence, especially early recurrence, and overall survival in patients with early-stage HCC after curative resection. We retrospectively reviewed the data of patients with early-stage HCC who underwent curative hepatectomy in the First Affiliated Hospital of Fujian Medical University (FHFU) and Mengchao Hepatobiliary Hospital of Fujian Medical University (MHH). Kaplan-Meier curves and Cox proportional hazards regression models were used to analyse disease-free survival (DFS) and overall survival (OS). Nomogram models were constructed on the datasets from the 70% samples of and FHFU, which were validated using bootstrap resampling with 30% samples as internal validation and data of patients from MHH as external validation. A total of 703 patients with early-stage HCC were included to create a nomogram for predicting recurrence or metastasis (DFS nomogram) and a nomogram for predicting survival (OS nomogram). The concordance indexes and calibration curves in the training and validation cohorts showed optimal agreement between the predicted and observed DFS and OS rates. The predictive accuracy was significantly better than that of the classic HCC staging systems.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Nomogramas , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Hepatectomia , PrognósticoRESUMO
The aim was to assess conditional survival for colon mucinous adenocarcinoma (MAC) patients, and to construct nomograms to predict conditional survival probability. Survival analysis was done using conditional survival, which was defined as the probability of surviving additional y years for patients who have survived for x years. The mathematical definition was express as: CS (y|x) = S (x + y)/S (x). Cox regression analyses were used to identify prognostic factors. A nomogram is constructed to predict conditional disease-free survival (DFS) and overall survival (OS) probability according to years that already survive. A total of 179 colon MAC patients were included. The 5-year DFS was 67% after surgery, and the 5-year survival probability of patients, who already survived 1, 2, 3, and 4 years were 75%, 87%, 95%, and 98%, respectively. The 5-year OS was 73% after surgery and increased to 76%, 82%, 88%, and 92% at 1, 2, 3, and 4 years, respectively. Subgroup analyses demonstrated the superiority of conditional survival was more pronounced in advanced stages than in stage I. And pT stage, pN stage, and lymphovascular invasion were significantly associated with DFS and OS. Conditional survival nomograms were constructed to predict the 5-year conditional DFS and OS probability given survival for 1, 2, 3, 4 years after surgery. Conditional survival can provide dynamic survival probability according to years that already survive, especially for patients with advanced stages. Taking into account the years already survived accounted for, novel nomograms contributed to effectively predicting conditional survival.