Risk factors for tumor enlargement in low-risk papillary thyroid microcarcinoma patients: a systematic review and meta-analysis.

PURPOSE: The current management guidelines for low-risk papillary thyroid microcarcinoma (PTMC) do not specify how to screen for growing tumors. We sought to explore the possible risk factors for tumor enlargement in patients with low-risk PTMC under active surveillance (AS). METHODS: We searched the PubMed and Embase databases for high quality studies up to January 10th, 2024. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included studies, and Review Manager 5.4 was used to analyze possible risk factors and calculate pooled risk ratios (RRs) via the inverse-variance calculation method. RESULTS: Eleven studies were included in our meta-analysis. Among the 8880 participants, 464 experienced tumor growth, and the incidence of tumor growth varied from 3.4% to 19.4%. The results of the meta-analysis showed that tumor enlargement was associated with younger age (pooled RR = 2.32, 95% CI = 1.85-2.90, p < 0.00001; 8 studies), and higher serum thyroid-stimulating hormone (TSH) levels (pooled RR = 2.28, 95% CI = 1.19-4.37, p = 0.01; 6 studies), and could be related to pregnancy (pooled RR = 2.54, 95% CI = 1.17-5.52, p = 0.02; 2 studies). However, these following factors showed no significant association with tumor growth: sex (pooled RR = 1.07, 95% CI = 0.63-1.84, p = 0.79; 7 studies), tumor size at diagnosis (pooled RR = 1.08, 95% CI = 0.63-1.85, p = 0.77; 5 studies), and Hashimoto's thyroiditis (HT) (pooled RR = 1.56, 95% CI = 0.93-2.60, p = 0.09; 2 studies). CONCLUSION: Our analysis identified that younger age and higher serum TSH levels were higher risk factors for tumor enlargement in low-risk PTMC patients. Pregnancy is a suspected risk factor.

The potential value of ultrasound in predicting local refractory/relapse events in primary thyroid lymphoma patients.

BACKGROUND: Primary thyroid lymphoma (PTL) is a rare malignant disorder, and ultrasound plays an important role in PTL diagnosis and follow-up surveillance. Prediction of refractory/relapse events in PTL patients is an essential issue, yet no ultrasonic PTL features have been discovered to be related to refractory/local relapse events. METHODS: From January 2008 to September 2022, newly diagnosed PTL patients in our center who underwent standard first-line treatment and received an ultrasound examination before treatment were enrolled. Data regarding patients' clinical and sonographic features, as well as their therapeutic responses were collected. Subjects with an ideal prognosis were compared to those with refractory/relapse events. RESULTS: In total, 37 PTL patients were analyzed, including 26 with diffuse large B-cell lymphoma, 2 with follicular lymphoma and 9 with mucosa-associated lymphoid tissue lymphoma. During the median follow-up of 25 months, 30 patients obtained a complete response, 4 were refractory patients, and 3 experienced local relapse. No significant difference was detected in the baseline clinical characteristics between patients with an ideal prognosis and those with refractory/local relapse events. In terms of sonographic features, however, an event-free survival (EFS) curve comparison revealed that patients with bilobar enlargement (defined as an anterior-posterior diameter > 2.5 cm on both sides of thyroid lobes) had a poorer EFS than those without (P < 0.0001), and patients with diffuse type had a poorer EFS than those with mixed/nodular types (P = 0.043). No significant difference was observed in EFS between patients with or without signs of suspicious cervical lymph node metastasis, rich blood signal distribution or symptoms of trachea compression. CONCLUSIONS: PTL patients with an anterior-posterior diameter > 2.5 cm for both thyroid lobes or PTL patients of the diffuse ultrasound type could be prone to refractory/local relapse events.

Prognostic Significance of KIF-12 Functioning as a Tumour Suppressor in Papillary Thyroid Carcinoma.

Objective: To explore the potential value of a novel marker, KIF-12, in the progression and prognosis of papillary thyroid carcinoma (PTC) through integrative bioinformatics analysis, and clinical sample validation of the prognostic value of KIF-12. Materials and Methods: We extracted the clinicopathological data of 502 PTC patients from The Cancer Genome Atlas-Thyroid Cancer (TCGA-THCA) dataset to identify reliable differentially expressed genes (DEGs) between high and low KIF12 expression groups. Functional enrichment analysis was performed on upregulated DEGs. Gene set enrichment analysis (GESA) was performed to identify the biological pathways. We further applied Cox analysis to determine independent risk factors associated with the PTC progression-free interval (PFI), and a nomogram was established to predict disease outcome. Finally, the prognostic value of KIF12 was validated by means of clinical samples from PTC patients with and without lateral lymph node metastasis. Results: On the basis of the TCGA-THCA database, we found that low KIF-12 expression was significantly related to a higher TNM stage (p<0.05), BRAF mutation status (p = 0.019), and extrathyroidal extension (p<0.001). KIF-12 was an independent prognostic factor of PTC (OR=0.319, 95% CI=0.130-0.784, P=0.013). The prognostic value of KIF12 was also successfully validated in clinical samples from twenty-nine PTC patients with lateral lymph node metastasis by comparison with twenty-two PTC patients without lymph node metastasis (P = 0.004). Conclusions: We report that KIF-12 has a tumor suppressive function in PTC and may be a useful prognostic tool to predict patient outcomes.

Gut microbiota dynamics and fecal SCFAs after colonoscopy: accelerating microbiome stabilization by Clostridium butyricum.

BACKGROUND: Colonoscopy is a classic diagnostic method with possible complications including abdominal pain and diarrhoea. In this study, gut microbiota dynamics and related metabolic products during and after colonoscopy were explored to accelerate gut microbiome balance through probiotics. METHODS: The gut microbiota and fecal short-chain fatty acids (SCFAs) were analyzed in four healthy subjects before and after colonoscopy, along with seven individuals supplemented with Clostridium butyricum. We employed 16S rRNA sequencing and GC-MS to investigate these changes. We also conducted bioinformatic analysis to explore the buk gene, encoding butyrate kinase, across C. butyricum strains from the human gut. RESULTS: The gut microbiota and fecal short-chain fatty acids (SCFAs) of four healthy subjects were recovered on the 7th day after colonoscopy. We found that Clostridium and other bacteria might have efficient butyric acid production through bioinformatic analysis of the buk and assessment of the transcriptional level of the buk. Supplementation of seven healthy subjects with Clostridium butyricum after colonoscopy resulted in a quicker recovery and stabilization of gut microbiota and fecal SCFAs on the third day. CONCLUSION: We suggest that supplementation of Clostridium butyricum after colonoscopy should be considered in future routine clinical practice.

Feasibility of whole-exome sequencing in fine-needle aspiration specimens of papillary thyroid microcarcinoma for the identification of novel gene mutations.

Genetic profiling is important for assisting the management of papillary thyroid microcarcinoma (PTMC). Although whole-exome sequencing (WES) of surgically resected PTMC tissue has been performed and revealed potential prognostic biomarkers, its application in PTMC fine-needle aspiration (FNA) specimens has not been explored. This study aimed to evaluate the feasibility of WES using FNA specimens of PTMC. Five PTMC patients were enrolled with clinical characteristics gathered. Fine aspiration cytology needle (23 gauges) was used to collect FNA biopsy with ultrasound guidance. WES analysis of FNA specimens from five PTMC patients and matched blood samples was performed. The WES of FNA samples yielded an average sequencing depth of 281× and average coverage of 99.5%. We identified 534 somatic single-nucleotide variants and 13 indels in total, and per sample, we found a mean of 24 exonic mutations, which affected a total of 120 genes. In the PTMC FNA samples, the most frequently mutated genes were BRAF and ANKRD18B, and the four driver genes were BRAF, AFF3, SRCAP, and EGFR. We also identified several germline cancer predisposing gene mutations. The results suggest that WES of FNA specimens is feasible for PTMC and can identify novel genetic mutations.

Gene mutations as predictors of central lymph mode metastasis in cN0 PTC: A meta-analysis.

Gene mutations could predict the tumor progression and prognosis, which are us to predict CLNM in patients with cN0 PTC, however, these results are not consistent. This meta-analysis tried to identify gene mutations which could predict CLNM in patients with cN0 PTC. A systematic search was performed for identifying relevant literature published prior to July 2023 in three search engines: PubMed, EMBASE and Web of Science. Studies that investigated the gene mutations for CLNM in patients with cN0 PTC were included in our meta-analysis. Sixteen studies, including 6095 cN0 PTC with BRAF mutations were include in our meta-analysis. The prevalence of CLNM in cN0 PTC ranged from 13.7% to 50.6%. The pooled analysis demonstrated that BRAFV600E mutation is significantly associated with CLNM (OR = 2.01, 95% CI: 1.55-2.60, p < 0.001) in PTC and PTMC (OR = 1.70, 95% CI: 0.51-1.81, p < 0.001). Whereas, cN0 PTC with TERT (OR = 1.94, 95% CI: 0.51-7.36, p = 0.33) and KRAS (OR = 0.57, 95% CI: 0.51-1.81, p = 0.34) mutations might not contribute to predict CLNM. Our analysis identified that BRAF mutation was a predictive factor for cN0 PTC, as well as for cN0 PTMC, which could be useful for clinician to accurately choose prophylactic CLND and better manage cN0 PTC.

Using preoperative ultrasound vascularity characteristics to estimate medullary thyroid cancer.

BACKGROUND: The early diagnosis of medullary thyroid carcinoma (MTC) is still a challenge in clinical practice. Based on ultrasound features, many MTC cases without suspicious characteristics are not categorized as high risk for malignancy. This study was designed to comprehensively investigate the ultrasonic features of MTC on ultrasound and help identify thyroid nodules with a high risk of MTC. METHODS: Between 2017 and 2023, we retrospectively reviewed 116 consecutive thyroid nodules with a histologic diagnosis of MTC who had undergone preoperative ultrasound examination. According to the ultrasonic criteria for risk classification, nodules were classified as "ultrasound-high suspicious" (h-MTC) and "ultrasound-low suspicious" (l-MTC). Using the same database, a tumour size- and risk evaluation-matched control group comprising 62 lesions was randomly selected to compare the vascularity features of l-MTC disease. RESULTS: We identified 85 h-MTC nodules (73.3%) and 31 l-MTC nodules (26.7%). For patients with l-MTC disease, 22/31 (71.0%) of the lesions were followed up for a period before fine needle aspiration (FNA) or surgery. We observed more penetrating branching vascularity in the l-MTC group than in the benign nodule group (23/31, 74.2% vs. 5/59, 4.8%, P < 0.001). We also showed that more CHAMMAS IV patterns (central blood flow greater than perinodular flow) (87.1% vs. 32.3%, P < 0.001)) and CHEN IV patterns (penetrating vascularity) (100% vs. 25.8%, P < 0.001) were found in l-MTC than benign nodules. CONCLUSIONS: Vascularity features can help differentiate l-MTC from benign nodules; moreover, we report a novel sonographic vascularity pattern of l-MTC disease, penetrating branching vascularity. The utilization of vascularity features will help to identify MTC among nodules with low-intermediate suspicion by ultrasound risk classification to ensure appropriate clinical management.

Qualitative and quantitative superb vascular imaging in the diagnosis of thyroid nodules ≤10 mm based on the Chinese Thyroid Imaging Reporting and Data System 4 (C-TIRADS 4).

Background: To compare qualitative and quantitative superb microvascular imaging (SMI) and determine the value of SMI in the diagnosis of thyroid nodules (TNs) ≤10 mm based on the Chinese Thyroid Imaging Reporting and Data System 4 (C-TIRADS 4). Methods: From October 2020 to June 2022, 106 patients with 109 C-TIRADS 4 (C-TR4) TNs (81 malignant, 28 benign) at the Peking Union Medical College Hospital were included. Qualitative SMI reflected the vascular pattern of the TNs and quantitative SMI was recorded by the vascular index (VI) of the nodules. Results: The VI was significantly higher in malignant nodules versus benign nodules both in the longitudinal (19.9±11.4 vs. 13.8±10.6, P=0.01) and transverse (20.2±12.1 vs. 11.3±8.7, P=0.001) sections. The area under the curve (AUC) of qualitative and quantitative SMI did not show a statistical difference in the longitudinal {0.657 [95% confidence interval (CI): 0.560-0.745] vs. 0.646 (95% CI: 0.549-0.735), P=0.79} and transverse [0.696 (95% CI: 0.600-0.780) vs. 0.725 (95% CI: 0.632-0.806), P=0.51] sections. Next, we combined qualitative and quantitative SMI to upgrade and downgrade the C-TIRADS classification. If a C-TR4B nodule had VIsum >12.2 or intra-nodular vascularity, the original C-TIRADS was upgraded to C-TR4C. If a C-TR4C or C-TR4B nodule manifested VIsum ≤12.2 and no intra-nodular vascularity, the original C-TIRADS was downgraded to C-TR4A. As a result, 18 C-TR4C nodules were downgraded to C-TR4A and 14 C-TR4B nodules were upgraded to C-TR4C. The new model of SMI + C-TIRADS showed high sensitivity (93.8%) and accuracy (79.8%). Conclusions: There is no statistical difference between qualitative and quantitative SMI in the diagnosis of C-TR4 TNs. The combination of qualitative and quantitative SMI may have the potential to manage diagnosis of C-TR4 nodules.

Shear wave elastography for differentiating parathyroid neoplasms with malignant diagnosis or uncertain malignant potential from parathyroid adenomas: initial experience.

OBJECTIVE: Parathyroid carcinoma (PC) and atypical parathyroid tumor (APT) are rare parathyroid disorders carrying the risk of recurrence of varying degrees. This study aims to explore the value of 2D-shear wave elastography (SWE) in the discrimination of PC/APT among suspicious parathyroid lesions. METHODS AND MATERIALS: In this prospective study, patients with primary hyperparathyroidism and suspicious parathyroid lesions on ultrasonography (US) were recruited. All the lesions were assessed by SWE before surgery. The velocity (m/s), Young's modulus (Kpa), and elastogram of SWE were compared between pathologically proven parathyroid carcinoma or atypical parathyroid tumor (Group1) and parathyroid adenoma (Group2). All the SWE parameters were displayed at the setting of 50 or 70 kPa. Correlations between SWE and the lesion size as well as biochemical parameters were analyzed. RESULTS: 36 target lesions were enrolled for analysis. The mean shear wave velocity (SWV) between the two groups was 2.4 m/s vs 1.9 m/s, respectively, while the mean Young's modulus was 11.1 kPa vs 18.2 kPa, respectively. The cut-off values are 2.35 m/s and 17.05 kPa correspondingly. The sensitivity and specificity of the selecting cut-off values were 0.56 vs 0.63 and 0.95 vs 1.0 (area under the curve [AUC]: 0.813 vs 0.852 [95% confidence interval (CI): 0.669-0.956 vs 0.720-0.983]; p <  0.001, p <  0.001; respectively). In contrast, the max SWV and Young's modulus showed a better sensitivity of 0.75 and 0.81, respectively. The "colored lesion" and "stiff rim" patterns on the elastogram are more indicated in parathyroid carcinoma and atypical parathyroid tumor, whereas the negative elastogram prevails in parathyroid adenoma. The SWV and Young's modulus of the parathyroid lesions were independent of the tumor size, but the max SWV and Young's modulus slightly correlated with serum parathyroid hormone concentration (PTH) (r = 0.398, p = 0.016; r = 0.396, p = 0.017). CONCLUSIONS: 2D-shear wave elastography plays a useful role in the preoperative assessment of parathyroid lesions with suspicious malignancy. The mean SWV and Young's modulus are advised as the favored diagnostic parameter with the best AUC and excellent specificities, while the max SWV and Young's modulus are more sensitive to distinguish the PC and APT compared with other parameters.

What Are the Characteristics of Papillary Thyroid Microcarcinoma Prone to High-Volume Lateral Lymph Node Metastasis? - An Analysis of 2981 Consecutive Cases.

PURPOSE: To identify candidate factors for predicting high-volume lateral lymph node metastasis (LLNM) in papillary thyroid microcarcinoma (PTMC). METHODS: We retrospectively studied 2981 patients with PTMC who underwent thyroidectomy from 2013 to 2016. LLNM was identified by histopathology. Patients with different LLNM statuses were compared according to clinical, sonographic and pathological parameters. A multivariate logistic model was established to predict high-volume LLNM (number of metastatic lymph nodes >5). RESULTS: High-volume LLNM of PTMC was independently associated with age < 40 years (OR = 1.791, P = 0.023), male sex (OR = 2.401, p = 0.001), tumor size > 0.5 cm (OR = 4.839, p < 0.001), extrathyroidal extension (OR = 2.097, p = 0.007) and microcalcification (OR = 2.894, p = 0.002). These five factors were incorporated together to develop a multivariate analysis, which showed good predictive ability (AUC = 0.78, 95% CI 0.72-0.83), with a sensitivity of 80.0% and a specificity of 61.4%. Moreover, more level II or V lateral regions were involved in patients with high-volume LLNM than in those with small-volume LLNM (69.2% vs. 25.0%, p < 0.001; 10.8% vs. 4.7%, p < 0.001). CONCLUSION: Multilevel LLNM tended to be more common in patients with PTMC who had high-volume LLNM. The high-volume LLNM rates of patients with PTMC with age < 40 years, male sex, tumor size > 0.5 cm, extrathyroidal extension and microcalcification were relatively higher than those without. These findings may be useful for identifying patients at higher high-volume LLNM risk who may require more aggressive treatment or intensive follow-up management.

Locoregional recurrence of parathyroid carcinoma: how to identify this rare but fatal condition using ultrasonography.

Parathyroid carcinoma (PC) is a rare condition with propensity to relapse. The purpose of this study was to evaluate the sonographic findings of locoregional recurrences of parathyroid carcinoma, in order to facilitate diagnosis of this condition using ultrasound (US). This was a retrospective observational study including 21 patients confirmed with pathologically confirmed locoregional recurrence of parathyroid carcinoma. All patients had undergone preoperative US examination at a tertiary center. The imaging, clinical and laboratory data of each case were collected. Sonographic appearance of the largest lesion at each recurrence was evaluated by two experienced radiologists according to a pre-agreed protocol. Overall, 29 relapses occurred in 21 patients. The median age of the patients was 45 years (range 24-71 years). The median size of the largest recurrent lesion at each relapse was 1.8 cm (range 0.8-3.8 cm). Ultrasound images showed hypoechoic solid nodules in 28 relapses (96.6%), inhomogeneous echo-texture in 28 relapses (96.6%), intralesional echogenic septa-like structures in 21 relapses (72.4%), intralesional cystic change in two relapses (6.9%), infiltrative or blurred boundary in 20 relapses (69.0%), irregular shape in 22 relapses (75.9%), marked vascularization on color Doppler imaging in 19 relapses (65.5%), multiple lesions in 26 relapses (89.7%), contralateral recurrence in 3 relapses (10.3%), and subcutaneous recurrence in 10 relapses (34.5%). None of the recurrent lesions exhibited calcification. The total size of all the recurrent lesions at each relapse fairly correlated with the serum intact parathyroid hormone levels (r = 0.450; p = 0.014).

Diagnostic Value of Sonographic Features in Distinguishing Malignant Partially Cystic Thyroid Nodules: A Systematic Review and Meta-Analysis.

Ultrasonography (US) is one of the most important methods for the management of thyroid nodules, which can be classified as solid, partially cystic, or cystic by composition. The various Thyroid Imaging Reporting and Data System classifications pay more attention to solid nodules and have reported pertinent US features associated with malignancy. However, the likelihood of malignancy of partially cystic thyroid nodules (PCTNs) is 3.3-17.6%, and few studies have systematically discussed the value of US in differentiating such entities. Therefore, we deemed it necessary to perform a systematic evaluation of US features in recognizing malignant PCTNs. Our systematic review and meta-analysis aimed to assess the value of US features in predicting malignant PCTNs. We searched the PubMed/MEDLINE, Web of Science, and Cochrane Library databases to find studies that researched US features of PCTNs and that were published before June 2020. Review Manager 5.3 was used to summarize suspicious US features and calculate the sensitivity, specificity, and likelihood ratios. MetaDiSc 1.4 was used to estimate receiver operating characteristic curves and calculate areas under the curves (AUCs). Our review included eight studies with a total of 2,004 PCTNs. Seven features were considered to be associated with malignancy. High specificity (>0.9) was found in nodules with a taller-than-wide shape, those that were spiculated/microlobulated or with an ill-defined margin, those with microcalcification, and a non-smooth rim. Among US features, eccentric configuration, microcalcification, and marked or mild hypoechogenicity were more reliable in predicting malignancy (AUC: 0.9592, 0.8504, and 0.8092, respectively). After meta-analysis, we recommend combining PCTN US features including an eccentric internal solid portion, marked or mild hypoechogenicity, and presence of microcalcification to better identify malignant nodules. More studies are needed to explore and improve the diagnostic value of US in PCTNs.

Robotic-assisted versus conventional laparoscopic surgery for colorectal cancer: Short-term outcomes at a single center.

BACKGROUND: The robotic technique has been established as an alternative approach to laparoscopy for colorectal surgery. The aim of this study was to compare the short-term outcomes of robot-assisted and laparoscopic surgery in colorectal cancer. METHODS: The cases of robot-assisted or laparoscopic colorectal resection were collected retrospectively between July 2015 and September 2018. We evaluated patient demographics, perioperative characteristics, and pathologic examinations. Short-term outcomes included time to passage of flatus and length of postoperative hospital stay. RESULTS: A total of 580 patients were included in the study. There were 271 patients in the robotic colorectal surgery (RCS) group and 309 in the laparoscopic colorectal surgery (LCS) group. The time to passage of flatus in the RCS group was 3.62 days shorter than the LCS group. The total costs were increased by 2,258.8 USD in the RCS group compared to the LCS group (P < 0.001). CONCLUSION: The present study suggests that colorectal cancer robotic surgery was more beneficial to patients because of a shorter postoperative recovery time of bowel function and shorter hospital stays.

Large-Volume Lateral Lymph Node Metastasis Predicts Worse Prognosis in Papillary Thyroid Carcinoma Patients With N1b.

We aimed to evaluate the relevance of large-volume lateral lymph node metastases (LLNMs) at risk of recurrence/persistence in papillary thyroid carcinoma (PTC) with LLNMs (N1b). This retrospective study included 448 PTC patients, who had positive LLNMs confirmed by histology and suspected of LLNMs by preoperative ultrasound. According to the number of pathological LLNMs, patients were divided into large-volume LLNM (number of LLNMs >5) and low-volume LLNM (number of LLNMs ≤5). Risk factors of recurrence/persistence in PTC patients with N1b were analyzed. Preoperative ultrasound features of PTC with large-volume LLNM were analyzed. For the patients with a mean follow-up of 44.0 months, the risk of recurrence/persistence was 25.1% in PTC patients with N1b. The recurrence/persistence rate was significantly higher in patients with large-volume LLNM than in patients with low-volume LLNM by multivariate analysis (37.3% vs. 17.1%; HR = 2.451, 95% CI 1.41-4.261, p = 0.001). The 3-year and 5-year recurrence/persistence-free survival for those with large-volume LLNM were 93.2% and 47.2%, respectively. Moreover, we found that multilevel suspected LLNMs and loss of fatty hilum were independent preoperative indicative factors of large-volume LLNM (OR = 6.239, 95% CI 3.547-10.977, p < 0.001; OR = 5.149, 95% CI 1.859-14.261, p = 0.002). In conclusion, multilevel suspected LLNM and loss of fatty hilum on ultrasound tended to be more common in patients with large-volume LLNM. PTC patients with large-volume LLNM are at a higher recurrent/persistent risk than those with low-volume LLNM. Large-volume LLNM may be used to stratify the risk of recurrence/persistence in PTC.

MicroRNA expression profiles identify biomarkers for predicting the response to chemoradiotherapy in rectal cancer.

Neoadjuvant chemoradiotherapy (nCRT) following surgery significantly improves the survival rate of patients with rectal cancer. However, nCRT is associated with significant adverse symptoms and high medical costs. Therefore, it is important to investigate potential biomarkers for the prediction of the response to nCRT in patients with rectal cancer. The present study identified candidate biomarkers for predicting a complete response (CR) to nCRT in patients with rectal cancer and investigated the associated mechanisms. Microarray data (accession no. GSE29298) was downloaded from the Gene Expression Omnibus database. Differentially expressed microRNAs (miRNAs/miR) were screened between the pathological CR (pCR) group and no pCR (incomplete response) group. miRNA target genes were predicted using the miRWalk 2.0 online tool and subjected to Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Furthermore, a miRNA co­regulatory network was constructed and disease­associated genes were predicted. The results demonstrated that a total of 36 upregulated and 5 downregulated miRNAs were identified between the two groups. Among these differentially expressed miRNAs, miR­548c­5p, miR­548d­5p and miR­663a were significantly associated with a CR to nCRT. The co­regulatory network and pathway analysis indicated that miR­548c­5p and miR­548d­5p may function together through stem cell pluripotency and ubiquitin­mediated proteolysis signaling pathways. Furthermore, the prediction of disease­associated genes demonstrated that miR­548c­5p/miR­548d­5p and miR­663a may regulate genes associated with rectal cancer, including mutated in colorectal cancers (MCC) and adenomatous polyposis coli (APC), and colorectal neoplasms, including interleukin­6 signal transducer (IL6ST), cell cycle checkpoint kinase 2 (CHEK2), marker of proliferation Ki­67 (MKI67), cadherin 7 (CDH7), calreticulin (CALR) and transforming growth factor ß1 (TGFB1). Therefore, miR­548c­5p, miR­548d­5p and miR­663a are promising candidate biomarkers for predicting a CR to nCRT. miR­548c­5p/miR­548d­5p may be associated with a CR by regulating IL6ST, CHEK2, MKI67 and MCC. In addition, it may function through the pluripotency of stem cells and ubiquitin­mediated proteolysis signaling pathways. miR­663a may be associated with a CR to nCRT by targeting CDH7, CALR, APC and TGFß1. Thus, the miRNA biomarkers investigated in the present study may represent novel therapeutic targets for the prediction and eventual improvement of the response to nCRT in patients with rectal cancer.

The expression and significance of microRNA in different stages of colorectal cancer.

BACKGROUND: The aim of this study is to compare microRNA expression patterns in different stages of colorectal cancer (CRC) and to discuss the significance of the application of microRNAs in the clinical treatment of CRC. METHODS: The study used gene chip technology to analyze genetic sequences in CRC tissues and surrounding normal tissues at different cancer stages. The bioinformatics profiles of the target genes of the different microRNAs were analyzed to clarify the target gene-related pathways and their functions in the disease. RESULTS: A total of 368 target genes with differential expression, including 275 upregulated and 93 downregulated genes, were screened from CRC patients in different stages of the disease. These microRNAs participated widely in the occurrence and development processes of CRC. The microRNA expression profiles obviously differed in tissues at different CRC stages. CONCLUSION: microRNA regulation of CRC samples can be used as a tool to control the occurrence and development of tumor cells.