establishing-competing-risk-regression-nomogram-model-for-survival

Establishing a Competing Risk Regression Nomogram Model for Survival Data

The Kaplan&#8211;Meier method and Cox proportional hazards regression model are the most common analyses in the survival framework. These are relatively ...

Second Affiliated Hospital of Zhejiang University School of Medicine

Zhejiang University

The features related to the prognosis of patients with mucinous breast cancer (MBC) remain controversial. We aimed to explore the prognostic factors of MBC and develop a nomogram for predicting survival outcomes.

Clinical Nomogram for Predicting Survival Outcomes in Early Mucinous Breast Cancer.

Signet ring cell carcinoma (SRCC) is a uniquely separated subgroup in metastatic colorectal cancer (mCRC). The aims are to investigate the value of resection in patients with resectable metastatic signet ring cell colorectal cancer.

Signet ring cell carcinoma of resectable metastatic colorectal cancer has rare surgical value.

Small intestinal neuroendocrine tumors (SiNETs) without distant metastasis typically behave in an indolent manner, but there can be heterogeneity. We aimed to define the survival outcomes and impacts of surgical intervention.

Survival outcomes and surgical intervention of small intestinal neuroendocrine tumors: a population based retrospective study.

The real-world occurrence rate of non-breast cancer-specific death (non-BCSD) and its impact on patients with breast cancer are poorly recognized.

Real-world impact of non-breast cancer-specific death on overall survival in resectable breast cancer.

There is no uniformly adopted cutoff value to define "young patients" with breast cancer. This study was designed to determine an optimal cutoff value, to investigate prognostic factors and to explore gene expression profiles of young female breast cancer.

How Young Is Too Young in Breast Cancer?-Young Breast Cancer Is Not a Unique Biological Subtype.

The effectiveness of the current Tumor, Lymph node, Metastases (TNM) staging system in small intestinal neuroendocrine tumors (SiNETs) is unsatisfactory. Current N classification only distinguishes between node-negative and node-positive status. We aim to refine the N classification for updated TNM stage.

The Lymph Node Ratio Optimizes Staging in Patients with Small Intestinal Neuroendocrine Tumors.

Although it is widely accepted that hormone receptor (HR) status is associated with later post-diagnostic periods, a debate exists as to whether the association is independent of age. The aim of our study was to confirm the impact of HR status on later period breast cancer-specific death (LP-BCSD) and later period non-breast cancer-specific death (LP-non-BCSD) in different age subgroups.

Young Patients with Hormone Receptor-Positive Breast Cancer Have a Higher Long-Term Risk of Breast Cancer Specific Death.

The number of reported young breast cancer cases has increased dramatically recently. The impact of age on the outcomes of breast cancers remains controversial. Our study aimed to explore the factors that can stratify the impact of young age on the prognosis of early breast cancer patients. In total, 244,324 patients with early breast cancer in the Surveillance, Epidemiology, and End Results database were identified from 1990 to 2007. Survival curves were generated using the Kaplan-Meier method. The 5- and 10-year cancer-specific survival (CSS) rates were calculated using the Life-Table method. Multivariable analyses were used to identify prognosti c variables (without age) to construct the nomograms. The risk score developed from the nomogram was used to classify the cohort into three subgroups (low-, medium- and high-risk subgroup). Approximately 8.89% of women were diagnosed with breast cancer at a young age (≤ 40 years). Clinical nomogram had the potential ability to predict CSS accurately with a well C-index (0.785). Subgroup analysis indicated that the risk score as the sole factor can stratify the impact of young age on the prognosis of early breast cancer patients. Young breast cancer patients had a worse prognosis in the low-risk (HR=0.61; 95% CI: 0.57-0.65; <0.001) or medium-risk subgroup (HR=0.89; 95% CI: 0.85-0.93; <0.01) than in the high-risk subgroup (=0.431). In conclusion, the worse prognosis of young women only appeared in the low- and medium-risk subgroups rather than in the high-risk subgroup. The risk score yielded from the nomogram model can assist clinical decision making for young breast cancer patients.

Young-onset breast cancer: a poor prognosis only exists in low-risk patients.

Although adjuvant chemotherapy is recommended for patients with stage II colon cancer characterized by poor prognostic features, its pros and cons remain a controversial issue. We aim to evaluate the real effectiveness of chemotherapy on stage II colon cancer as well as select suitable patients.

De-escalating chemotherapy for stage II colon cancer?

Senescent microenvironments play an important role in tumor progression. Here, we report that doxorubicin (DOX)-pretreated or replicative senescent stromal cells (WI-38 and HUVEC) promote colorectal cancer (CRC) cell growth and invasion in vitro and in vivo. These pro-tumorigenic effects were attenuated by exogenous administration of Klotho, an anti-aging factor. We subsequently identified several senescence-associated secretory phenotype (SASP)-associated genes, including CCL2, which were significantly upregulated in both types of senescent stromal cells during replication and DNA damage-induced senescence. Importantly, we found that the secretion of CCL2 by senescent stromal cells was significantly higher than that seen in nonsenescent cells or in senescent cells pretreated with Klotho. Notably, CCL2 was found to accelerate CRC cell proliferation and invasion, while this effect could be blocked by administration of a specific CCR2 antagonist. We further show that Klotho can suppress NF-κB activation during DOX-induced senescence and thus block CCL2 transcription. Low expression of Klotho, or high expression of CCL2 in patient tumor tissues, correlated with poor overall survival of CRC patients. Collectively, our findings suggest that senescent stromal cells are linked to progression of CRC. Klotho can suppress the senescent stromal cell-associated triggering of CRC progression by inhibiting the expression of SASP factors including CCL2. The identification of key SASP factors such as CCL2 may provide potential therapeutic targets for improving CRC therapy.

Klotho-mediated targeting of CCL2 suppresses the induction of colorectal cancer progression by stromal cell senescent microenvironments.

Gastric cancer (GC) patients with metastasis had limited treatment options and dismal outcome. We have previously reported the aberrant expression of Zic family member 1 (Zic1) in GC. However, the functional roles and underlying mechanism of Zic1 in GC metastasis remain unknown. Here, we demonstrate that lower expression of Zic1 was correlated with more lymph node metastasis and poor outcome of GC patients. Ectopic expression of Zic1 suppressed both lung metastasis and peritoneal tumor dissemination of GC in mice. The metastatic suppressing ability of Zic1 was mediated by regulating the process of cell invasion, adhesion and epithelial-mesenchymal transition (EMT). Mechanistically, Zic1 could downregulate Wnt targets including c-Myc and Cyclin D1 by inhibiting LEF transcriptional activity in GC cells. Notably, Zic1 was inversely related to the expression of Cyclin D1 in GC tissues tested. In addition, Zic1 could physically interact with β-catenin/transcription factor 4 (TCF4) and disrupt their complex formation, while not affecting β-catenin nuclear localization. Collectively, our study indicated that Zic1 suppressed GC metastasis through attenuating Wnt/β-catenin signaling and the EMT process. Our work may provide novel therapeutic strategies for the metastasis of GC.

Zic1 suppresses gastric cancer metastasis by regulating Wnt/β-catenin signaling and epithelial-mesenchymal transition.

Clinically, a considerable portion of patients with early T stage who were supposed to have a low distant metastatic probability were diagnosed with metastatic liver colorectal cancer (CRLM). Our study aims to evaluate the prognostic value of the T stage for metastatic patients and establish a convenient individual assessment model for clinicians to explore preoperative predictors. The mRNA profiles of colorectal tumors ( = 19) were obtained by microarray at our clinical center. A total of 5,618 patients with CRLM from 2010 to 2015 were enrolled for the Surveillance, Epidemiology, and End Results (SEER) database. The cDNA microarray analyses showed that gene expression pattern in the T2N0M1 subgroup was significantly different from the T3/4N0M0 subgroup. In the survival analysis, metastatic patients with T1 stage surprisingly had much poorer prognosis than those with T3/T4 stage. Specifically, metastatic patients with early T stage were observed with higher frequency occurring at the rectum, better differentiation, less metastases in the lymph nodes, and a higher CEA level. Further survival analysis indicated that early T classification was an independent prognostic factor for a poor survival. When the lymph node (N) status was taken into consideration, patients with T1/2N+ had better survival than T1/2N0 patients. A clinical nomogram was constructed based on preoperative factors. The calibration curves showed a good concordance between nomogram prediction and actual observation. In conclusion, CRLM with early T stage had a different biological background. The prognosis of patients at T1/2M1 was poorer than at T3/4M1. More attention should be paid to the surveillance of high-risk factors and the screening of early T stage.

Article	Year
Clinical Nomogram for Predicting Survival Outcomes in Early Mucinous Breast Cancer. PloS one\| PubMed ID: 27760180	2016
Signet ring cell carcinoma of resectable metastatic colorectal cancer has rare surgical value. Journal of surgical oncology\| PubMed ID: 27891617	2016
Survival outcomes and surgical intervention of small intestinal neuroendocrine tumors: a population based retrospective study. Oncotarget\| PubMed ID: 27903960	2017
Real-world impact of non-breast cancer-specific death on overall survival in resectable breast cancer. Cancer\| PubMed ID: 28267199	2017
How Young Is Too Young in Breast Cancer?-Young Breast Cancer Is Not a Unique Biological Subtype. Clinical breast cancer\| PubMed ID: 28802528	2018
The Lymph Node Ratio Optimizes Staging in Patients with Small Intestinal Neuroendocrine Tumors. Neuroendocrinology\| PubMed ID: 29920478	2018
Young Patients with Hormone Receptor-Positive Breast Cancer Have a Higher Long-Term Risk of Breast Cancer Specific Death. Journal of breast cancer\| PubMed ID: 30941237	2019
Young-onset breast cancer: a poor prognosis only exists in low-risk patients. Journal of Cancer\| PubMed ID: 31289582	2019
De-escalating chemotherapy for stage II colon cancer? Therapeutic advances in gastroenterology\| PubMed ID: 31489031	2019
Klotho-mediated targeting of CCL2 suppresses the induction of colorectal cancer progression by stromal cell senescent microenvironments. Molecular oncology\| PubMed ID: 31545552	2019
Zic1 suppresses gastric cancer metastasis by regulating Wnt/β-catenin signaling and epithelial-mesenchymal transition. FASEB journal : official publication of the Federation of American Societies for Experimental Biology\| PubMed ID: 31909528	2020
Early T Stage Is Associated With Poor Prognosis in Patients With Metastatic Liver Colorectal Cancer. Frontiers in oncology\| PubMed ID: 32626650	2020

Lunpo Wu

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