ObjectiveTo detect the expression of Krüppel like factor 8 (KLF8) in breast cancer tissues and cells and to explore the clinical significance of KLF8.Methods① The Oncomine database was used to analyze the differential expression of KLF8 mRNA in the breast cancer tissues. The Kaplan-Meier Plotter database was used to analyze the relationship between KLF8 mRNA expression and prognosis (relapse free survival, overall survival, post-progression survival, and distant metastasis-free survival) of patients with breast cancer. ② The quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the KLF8 expression levels in the 16 clinical patients with breast cancer and 7 breast cancer cell lines (MDA-MB-231, MCF-12A, Hs-578T, MCF-7, BT-474, MDA-MB-453, ZR-75-30) and normal breast epithelial cell lines MCF-10A, and the immunofluorescence was used to further detect the localization of KLF8 expression in the 2 breast cancer cell lines with higher KLF8 expression level. ③ The immunohistochemistry was used to detect the expression of KLF8 protein in 135 cases of breast cancer tissue microarrays, and the relationships between KLF8 protein expression and clinicopathologic characteristics or overall survival were analyzed.Results① The Oncomine database showed that KLF8 mRNA expression in the breast cancer tissues was higher than that in the normal breast tissues (P<0.001). The median KLF8 mRNA expression level was taken as the cut-off point for high or low KLF8 expression. The results of Kaplan-Meier Plotter data analysis showed that the prognosis (relapse free survival, overall survival, postprogression survival, and distant metastasis-free survival) of patients with low KLF8 mRNA expression were better than those of patients with high KLF8 mRNA expression (P<0.05). ② The results of qRT-PCR and Western blot all showed that the KLF8 mRNA and protein expression levels in the breast cancer tissues were higher than those in the adjacent normal tissues (P=0.002, P<0.001). In addition, the Western blot results showed that the expression of KLF8 protein in the 7 breast cancer cell lines was higher than that in the normal breast epithelial cell lines MCF-10A respectively, and KLF8 protein mainly expressed in the cytoplasm of breast cancer cells and highly expressed in the nuclear of a few cells. ③ There were 63 cases of high KLF8 expression and 72 cases of low KLF8 expression by the immunohistochemical analysis of 135 patients with breast cancer tissue microarray (the H-score of the immunohistochemical test results was 75 as the cut-off point, H-score >75 was the high KLF8 expression and H-score ≤75 was the low KLF8 expression), the differences of statuses of estrogen receptor (ER) and progesterone receptor (PR) between the patient with high KLF8 expression and low KLF8 expression were significant (P<0.05). The Kaplan-Meier survival curve analysis showed that the prognosis of patients with high KLF8 expression was worse than that of patients with low KLF8 expression (P=0.002). The univariate analysis showed that the TNM stage, statuses of ER and PR, and KLF8 expression were related to the prognosis of patients with breast cancer (P<0.05), further multivariate Cox proportional hazards regression analysis indicated that the later stage of TNM and high KLF8 expression were the independent risk factors (P<0.05).ConclusionsThe results of this study suggest that KLF8 highly expresses in both breast cancer tissues and breast cancer cells, which is related to the statuses of ER and PR and prognosis of patients with breast cancer. KLF8 might be involved in the progression of breast cancer as an oncogenic gene, or it might provide a new direction for prognosis judgment and molecular targeted therapy of breast cancer.
ObjectiveTo analyze the clinicopathologic features of thyroid tumors with RAS gene mutation.MethodThe clinicopathologic data of thyroid tumor patients who underwent surgical treatment or biopsy and were diagnosed pathologically at the Department of Pathology of the Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2021 to June 2023, were collected. ResultsA total of 798 patients with thyroid tumors who met the inclusion criteria were collected, including 747 cases of follicular epithelial tumors and 51 cases of medullary thyroid carcinoma (MTC). Among 798 patients, the RAS gene mutations were detected in 36 cases (4.5%), including 25 (69.4%) patients with NRAS mutations, 8 (22.2%) patients with HRAS mutations, 3 (8.3%) patients with KRAS mutations, and 4 (1.1%) patients accompanied with TERT promoter mutations. Among 36 patients with RAS mutant thyroid tumors, the male to female ratio was 7∶11, with a median age of 48.5 years, with an average tumor diameter of 2 cm. The mutation rate of RAS gene in different histological types of thyroid tumors, from high to low, was highest in the thyroid follicular carcinoma (FTC, 25.9%), followed by differentiated high grade thyroid carcinoma (20.0%), anaplastic thyroid carcinoma (20.0%), noninvasive follicular thyroid neoplasm with papillary like nuclear features (18.2%), follicular variant of papillary thyroid carcinoma (FVPTC, 16.0%), and well-differentiated thyroid tumour of uncertain malignant potential (WT-UMP, 12.8%), the mutation rates of RAS gene in the FTC, FVPTC, and WT-UMP were significantly higher than that of the classical papillary thyroid carcinoma (P<0.001 1), and the mutation rate of RAS gene was the lowest in the classical papillary thyroid carcinoma (1.5%). A total of 35 patients were effectively followed up with an average follow-up period of 21.4 months, 6 of whom had cervical lymph node metastasis, 4 patients developed distant metastasis, and 1 patient with anaplastic thyroid carcinoma died. ConclusionsRAS gene mutation can occur in thyroid follicular differentiated tumors and MTC. NRAS mutation is more common. The mutation rate is the highest in FTC, is the lowest in classical papillary thyroid carcinoma. Differential diagnosis combined with tissue morphology and other molecular changes can provide a reference for guiding treatment and evaluating prognosis.
Objective To investigate the differences in clinicopathological characteristics and prognostic survival of human epidermal growth factor receptor 2 (HER2) high expression, HER2 low expression and HER2 negative breast cancer. MethodWe retrospectively collected 1 560 female breast cancer patients who underwent surgical treatment at the Department of Breast and Thyroid Surgery in Renmin Hospital of Wuhan University between January 8, 2010 and December 31, 2015, and divided them into high expression group, low expression group and negative group according to HER2 expression, to compare the differences in clinicopathological characteristics among the three groups of breast cancer patients and to explore the factors influencing prognosis. Results The proportions of histological grade Ⅲ, tumor diameter >2 cm, lymph node metastasis, TNM stage Ⅲ, Ki67 high expression, and hormone receptor negative expression were higher in the high expression group than those in the low expression group and negative group (P<0.050); the proportions of histological grade Ⅲ, tumor diameter >2 cm, lymph node metastasis, and TNM stage Ⅲ were higher in the low expression group than those in the negative group (P<0.050). However, the proportions of Ki67 high expression and hormone receptor negative expression were lower than those of the negative group (P<0.050). The 5-year disease-free survival rate were 85.6%, 80.3% and 74.5% for the high expression, low expression and negative group, respectively, and the 5-year overall survival rate were 90.4%, 86.0% and 80.7%, respectively. The results of multivariate Cox proportional hazard model showed that patients with high histological grade, late TNM stage, Ki67 high expression and weaker HER2 expression intensity had worse 5-year disease-free survival (P<0.050); patients with older age, high histological grade, lymph node metastasis, late TNM stage, Ki67 high expression and weaker HER2 expression intensity had worse 5-year overall survival (P<0.050). Conclusions The intensity of HER2 expression affects the 5-year disease-free survival and overall survival of breast cancer patients, and the higher the intensity of HER2 expression, the better the 5-year disease-free survival and overall survival, while the weaker the HER2 expression, the worse the 5-year disease-free survival and overall survival.
Objective To investigate the correlation between the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic immune inflammation index (SII) and clinicopathological characteristics and prognosis in patients with gastrointestinal stromal tumor (GIST). Methods The clinicopathological data and blood routine results of 101 patients with GIST who were treated surgically in the General Hospital Western Theater Command PLA from December 2014 to December 2018 were collected retrospectively, samples were obtained to calculate NLR, PLR and SII. The optimal cutoff value of NLR, PLR and SII were evaluated by receiver operating characteristic (ROC) curve. The Chi-square test and t-test were used to analyze the relationship between NLR, PLR, SII and clinicopathological characteristics of GIST. The Kaplan-Meier plots and the log-rank test were used to analyze the influence factors affecting the recurrence-free survival (RFS) of patients with GIST. Multivariate Cox regression analyses was used to identify the independent influence factors affecting the RFS of patients with GIST. Results The preoperative peripheral blood NLR, PLR and SII of patients with GIST were correlated with the tumor site, tumor diameter and modified NIH risk stratification (P<0.05), but not with the mitotic count of tumor cells (P>0.05). Kaplan-Meier plots and log-rank test showed that NLR, PLR, SII, surgical method, tumor site, tumor diameter, mitosis rate and modified NIH risk stratification were the influential factors of RFS in with GIST. The multivariate Cox regression analysis revealed that postoperative whether to accept regular imatinib adjuvant therapy (HR=32.876, P<0.001), modified NIH risk stratification (HR=129.182, P<0.001), and PLR (HR=5.719, P=0.028) were independent influence factors affecting the RFS of patients with GIST. Conclusions Preoperative peripheral blood PLR, NLR, and SII are correlated with clinicopathological characteristics such as the tumor location, tumor diameter and modified NIH risk stratification, and are the influencing factors of postoperative RFS in patients with GIST. PLR is an independent predictor of RFS in patients with GIST.
ObjectiveTo compare the clinicopathological characteristics of breast invasive micropapillary carcinoma (IMPC) with different composition ratios, and analyze the relationship between proportion of micropapillary carcinoma components and the prognosis of IMPC. Methods The related data of 121 patients with invasive ductal carcinoma (IDC) complicated with IMPC who were treated in the Department of Breast Surgery, Affiliated Hospital of Southwest Medical University from August 2016 to August 2020 were collected. With micropapillary carcinoma accounting for 50%, the patients were divided into IMPC <50% group and IMPC ≥50% group. The correlation between related clinicopathological features and prognosis of patients was analyzed. Results There were 85 patients in the IMPC <50% group and 36 patients in the IMPC ≥50% group. The analysis results showed that there was no significant differences between the two groups in menstrual status, histological grade, molecular typing, TNM stage, age, immunohistochemical expression, neoadjuvant therapy, nerve invasion, nipple invasion, and skin invasion (P>0.05). The rate of lymphatic vessel invasion (LVI) in the IMPC ≥50% group was 83.33% (30/36), which was significantly higher than 61.18% (52/85) in the IMPC <50% group, and the difference between the two groups was statistically significant (χ2=5.684, P=0.017). Kaplan-Meier survival curve was drawn, and the analysis results showed that the 3-year cumulative disease-free survival (DFS) of IMPC patients was correlated with the number of lymph node metastasis and LVI (P<0.05). And with the estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, Ki-67, molecular typing, proportion of micropapillary carcinoma components and histological grade were unrelated (P>0.05). The results of multivariate Cox risk regression analysis showed that the number of lymph node metastases and LVI were independent prognostic factors affecting DFS in patients. Conclusions When the proportion of IMPC component is ≥50%, the LVI rate of tumor is higher than that of IMPC component <50%. The number of lymph node metastasis and LVI are independent prognostic factors affecting DFS in IMPC patients.
ObjectiveTo systematicly evaluate expression of epithelial cell adhesion molecule (EpCAM) in colorectal cancer (CRC) and its correlation with clinicopathologic characteristics of patient with CRC.MethodsPubMed, Web of Science, Cochrane Library, Embase, CNKI, Wanfang, VIP, and other databases were searched comprehensively. The retrieved literatures were imported into Endnote X9. The data about the expression of EpCAM in the CRC and the relationship between EpCAM expression and clinicopathologic characteristics of patients with CRC were screened and extracted. RevMan 5.3 software was used for meta-analysis.ResultsA total of 5 396 patients with CRC were included. The meta-analysis results showed that the expression rate of EpCAM in the CRC tissues or blood was significantly higher than that in the benign colorectal tumor and normal tissue or blood (P<0.05). The high expression rates of EpCAM in the Dukes C+D stage, tumor diameter >3 cm, infiltration state of tumor margin, with lymph node and distant metastasis of the CRC were significantly higher than those in the A+B stage, tumor diameter ≤3 cm, dilated state of tumor margin, without lymph node and distant metastasis (P<0.05).ConclusionResults of this meta-analysis suggest that expression of EpCAM might be related to some clinicopathologic characteristics (carcinogenesis, Dukes stage, tumor size, tumor margin morphology, lymph node metastasis, distant metastasis) of patients with CRC.
Objective To investigate the prognostic differences and decision-making role in postoperative radiotherapy of four molecular subtypes in pT1-2N1M0 stage breast cancer. Methods The clinicopathological data of 1526 patients with pT1-2N1M0 breast cancer treated at West China Hospital of Sichuan University between 2008 and 2018 were retrospectively analyzed. χ2 test was used to compare the clinicopathological features among patients with different molecular subtypes. Kaplan-Meier survival analysis and log-rank test were used to draw the survival curves and compare the overall survival (OS) and breast cancer-specific survival (BCSS) among patients with different molecular subtypes. Cox regression model was used to determine the influencing factors of OS of patients after radical mastectomy. Results Among the 1526 patients with pT1-2N1M0 breast cancer, there were 674 cases (44.2%) of Luminal A subtype, 530 cases (34.7%) of Luminal B subtype, 174 cases (11.4%) of human epidermal growth factor receptor 2 (Her-2) overexpression subtype, and 148 cases (9.7%) of triple-negative subtype. The 5-year OS rates of Luminal A, Luminal B, Her-2 overexpression and triple negative patients were 98.6%, 94.3%, 95.5% and 91.2%, respectively (χ2=11.712, P=0.001), and the 5-year BCSS rates were 99.3%, 94.6%, 95.5% and 92.5%, respectively (χ2=18.547, P<0.001). Multiple Cox regression analysis showed that menstrual status [hazard ratio (HR)=0.483, 95% confidence interval (CI) (0.253, 0.923), P=0.028] and whether endocrine therapy [HR=2.021, 95%CI (1.012, 4.034), P=0.046] were prognostic factors for the 5-year OS rate of breast cancer patients after radical mastectomy (P<0.05). However, it failed to reveal that Luminal subtypes and postoperative radiotherapy were prognostic factors for the 5-year OS rate (P>0.05). Conclusions In pT1-2N1M0 breast cancer patients, the 5-year OS rate and 5-year BCSS rate in triple-negative patients are the lowest. The relationship between Luminal classification, postoperative radiotherapy and survival in patients after radical mastectomy needs further study in the future.
ObjectiveTo investigate the relationship between clinicopathologic characteristics of patients with papillary thyroid carcinoma (PTC) and diabetes mellitus (DM), and to provide basis for individualized diagnosis and treatment.MethodsThe patients who underwent the first thyroid surgery in the Renmin Hospital of Wuhan University from January 1, 2017 to September 15, 2020 and were pathologically diagnosed as PTC were collected. According to the presence or absence of DM, the clinical features were compared.ResultsThere were 2859 patients without DM and 133 patients with DM in 2992 patients. In patients with or without DM, there were no differences in lymph node metastasis, multiple, bilateral tumors, and extrathyroid invasion between the two groups (P>0.05). However, compared with the PTC patients without DM, the proportion of women with DM was lower (58.65% versus 76.71%, P<0.01), the proportions of age >55 years old (92.48% versus 66.32%, P<0.01) and capsule invasion (67.21% versus 63.11%, P=0.04) with DM were higer. After adjusting for age and gender, the multivariate analysis showed that the risks of larger tumor and capsular invasion in the patients with DM was 1.51 times [95%CI (1.06, 2.16), P=0.02] and 1.75 times [95%CI (1.16, 2.64), P<0.01] respectively as compared with in the patients without DM.ConclusionsIn PTC patients with DM, proportion of women is lower, proportions of elderly population (age >55 years old) and patients with capsular invasion are higer, tumor is larger. Therefore, patients with DM must not neglect regular examination of thyroid morphology and function, and PTC patients should also pay attention to control of blood glucose.
Objective To detect the expression of copine 1 (CPNE1) in the gastric cancer (GC) and investigate its association with prognosis. MethodsThe clinicopathologic data of 121 patients who underwent radical gastrectomy in the Department of General Surgery, The 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation Army from March 2017 to December 2018 were retrospectively collected. The protein expression of CPNE1 in the GC tissues was detected by immunohistochemical (IHC) staining, and its association with prognosis was analyzed. GC tissues and adjacent tissues samples from 16 patients in the same time were prospectively collected, and the mRNA and protein expressions of CPNE1 were detected by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Multivariate Cox proportional hazards regression model was used to analyze the prognostic factors of GC patients. ResultsIHC staining results showed that the CPNE1 was mainly expressed in the cell membrane and cytoplasm of gastric epithelial cells, and the color showed different degrees of brown. Among the 121 patients, 70 (57.9%) had high CPNE1 protein expression and 51 (42.1%) had low CPNE1 protein expression. The RT-qPCR and WB results of 16 pairs of fresh tissue specimens showed that the expression levels of CPNE1 mRNA and protein in the GC tissues were higher than those in the corresponding adjacent tissues (CPNE1 mRNA mean value: 1.451 vs. 1.100, P=0.048; CPNE1 protein mean value: 0.995 vs. 0.521, P=0.001). The multivariate Cox proportional hazards regression analysis showed that the high protein expression of CPNE1 [HR (95%CI)=1.931 (1.123, 3.321), P=0.017] was the risk factor affecting the prognosis of the patients with GC. ConclusionCPNE1 highly expresses in GC tissues and is associated with a poor prognosis in patients with GC, and it may be a potential tumor biomarker.
ObjectiveTo elucidate the clinical and pathological features and review the progress of diagnosis and treatment in patients with brain metastasis (BM) from colorectal cancer (CRC), so as to provide a reference for the whole process management for patients with BM from CRC in China.MethodThe latest research results and previous literatures about patients with BM from CRC were reviewed.ResultsThe prognosis of BM from CRC was poor, its molecular pathological mechanism was complex and diverse, and some risk factors associated with the occurrence of BM had been identified. Typical imaging features of BM from CRC were helpful to the diagnosis of patients. At present, radiotherapy was still the main treatment. Bevacizumab treatment or immunotherapy combined with radiotherapy was expected to improve the survival of BM from CRC.ConclusionScientific and standardized prevention, diagnosis, and treatment are beneficial to reduce incidence of BM from CRC and improve survival.