FoxM1 Is Associated with Poor Prognosis of Non-Small Cell Lung Cancer Patients through Promoting Tumor Metastasis

Background

FoxM1 has been reported to be important in initiation and progression of various tumors. However, whether FoxM1 has any indication for prognosis in non-small cell lung cancer patients remains unclear.

Methodology/Principal Findings

In this study, FoxM1 expression in tumor cells was examined first by immunohistochemistry in 175 NSCLC specimens, the result of which showed that FoxM1 overexpression was significantly associated with positive smoking status (P = 0.001), poorer tissue differentiation (P = 0.0052), higher TNM stage (P<0.0001), lymph node metastasis (P<0.0001), advanced tumor stage (P<0.0001), and poorer prognosis (P<0.0001). Multivariable analysis showed that FoxM1 expression increased the hazard of death (hazard ratio, 1.899; 95% CI, 1.016–3.551). Furthermore, by various in vitro and in vivo experiments, we showed that targeted knockdown of FoxM1 expression could inhibit the migratory and invasive abilities of NSCLC cells, whereas enforced expression of FoxM1 could increased the invasion and migration of NSCLC cells. Finally, we found that one of the cellular mechanisms by which FoxM1 promotes tumor metastasis is through inducing epithelial-mesenchymal transition (EMT) program.

Conclusions

These results suggested that FoxM1 overexpression in tumor tissues is significantly associated with the poor prognosis of NSCLC patients through promoting tumor metastasis.     

PTK 7 Is a Transforming Gene and Prognostic Marker for Breast Cancer and Nodal Metastasis Involvement

Protein Tyrosin Kinase 7 (PTK7) is upregulated in several human cancers; however, its clinical implication in breast cancer (BC) and lymph node (LN) is still unclear. In order to investigate the function of PTK7 in mediating BC cell motility and invasivity, PTK7 expression in BC cell lines was determined. PTK7 signaling in highly invasive breast cancer cells was inhibited by a dominant-negative PTK7 mutant, an antibody against the extracellular domain of PTK7, and siRNA knockdown of PTK7. This resulted in decreased motility and invasivity of BC cells. We further examined PTK7 expression in BC and LN tissue of 128 BC patients by RT-PCR and its correlation with BC related genes like HER2, HER3, PAI1, MMP1, K19, and CD44. Expression profiling in BC cell lines and primary tumors showed association of PTK7 with ER/PR/HER2-negative (TNBC-triple negative BC) cancer. Oncomine data analysis confirmed this observation and classified PTK7 in a cluster with genes associated with agressive behavior of primary BC. Furthermore PTK7 expression was significantly different with respect to tumor size (ANOVA, p = 0.033) in BC and nodal involvement (ANOVA, p = 0.007) in LN. PTK7 expression in metastatic LN was related to shorter DFS (Cox Regression, p = 0.041). Our observations confirmed the transforming potential of PTK7, as well as its involvement in motility and invasivity of BC cells. PTK7 is highly expressed in TNBC cell lines. It represents a novel prognostic marker for BC patients and has potential therapeutic significance.     

CD271+ Subpopulation of Pancreatic Stellate Cells Correlates with Prognosis of Pancreatic Cancer and Is Regulated by Interaction with Cancer Cells

Pancreatic stellate cells (PSCs) play a crucial role in the aggressive behavior of pancreatic cancer. Although heterogeneity of PSCs has been identified, the functional differences remain unclear. We characterized CD271⁺ PSCs in human pancreatic cancer. Immunohistochemistry for CD271 was performed for 31 normal pancreatic tissues and 105 pancreatic ductal adenocarcinomas (PDACs). We performed flow cytometry and quantitative RT-PCR, and assessed CD271 expression in PSCs isolated from pancreatic tissues and the changes in CD271 expression in PSCs cocultured with cancer cells. We also investigated the pattern of CD271 expression in a SCID mouse xenograft model. In the immunohistochemical analyses, the CD271-high staining rates in pancreatic stroma in normal pancreatic tissues and PDACs were 2/31 (6.5%) and 29/105 (27.6%), respectively (p = 0.0069). In PDACs, CD271⁺ stromal cells were frequently observed on the edge rather than the center of the tumors. Stromal CD271 high expression was associated with a good prognosis (p = 0.0040). Flow cytometric analyses demonstrated CD271-positive rates in PSCs were 0–2.1%. Quantitative RT-PCR analyses revealed that CD271 mRNA expression was increased in PSCs after coculture with pancreatic cancer cells. However, the level of CD271 mRNA expression subsequently decreased after the transient increase. Furthermore, CD271 mRNA expression was decreased in PSCs migrating toward pancreatic cancer cells through Matrigel. In the xenograft model, CD271⁺ PSCs were present at tumor margins/periphery and were absent in the tumor core. In conclusion, CD271 was expressed in PSCs around pancreatic tumors, but not in the center of the tumors, and expression decreased after long coculture with pancreatic cancer cells or after movement toward pancreatic cancer cells. These findings suggest that CD271⁺ PSCs appear at the early stage of pancreatic carcinogenesis and that CD271 expression is significantly correlated with a better prognosis in patients with PDAC.     

Ratio between Negative and Positive Lymph Nodes Is Suitable for Evaluation the Prognosis of Gastric Cancer Patients with Positive Node Metastasis

Objective

To date, there is no consensus to evaluate the most appropriate category of the nodal metastasis for precise predication the prognosis of gastric cancer patients with positive node metastasis after curative surgery.

Methods

We retrospectively analyzed the clinicopathologic characteristics and overall survival (OS) of 299 gastric cancer patients with positive node metastasis after curative surgery for evaluation the optimal category of the nodal metastasis.

Results

With the univariate and multivariate survival analyses, the depth of primary tumor invasion was identified as the independent predicators with the OS of 299 gastric cancer patients with nodal metastasis postoperatively, as were the number of positive lymph nodes (PLNs), the number of negative lymph nodes (NLNs), and the ratio between negative and positive lymph nodes (RNPL). The RNPL was identified to be more suitable for predication the OS of gastric cancer patients with positive node metastasis than the ratio between positive and dissected lymph nodes (RPDL) by using the stratum procedure of survival analysis. Besides, we found both PLNs and NLNs were independently correlated with OS of gastric cancer patients with nodal metastasis when RNPL, instead of RPDL, was controlled in the partial correlation model.

Conclusions

RNPL, a new category of the nodal metastasis, was suitable for predication the OS of gastric cancer patients with nodal metastasis after curative resection, as were the PLNs, and NLNs.     

Analysis of Lymph Node Metastasis Correlation with Prognosis in Patients with T2 Gastric Cancer

Purpose

To investigate the correlated factors for lymph node metastasis and prognosis for patients with T2 gastric cancer.

Methods

A total of 442 patients with T2 gastric cancer who underwent gastrectomy from January 1996 to December 2009 were evaluated. The clinicopathological parameters were analyzed for lymph node metastasis and prognosis, including gender, age, tumor size, tumor location, histological type, depth of invasion, vascular tumor emboli, nervous invasion, resection type, and pathological stage.

Results

The rate of lymph node metastasis was 45.9%. Univariate analysis showed that depth of invasion, tumor size, and vascular tumor emboli were associated with lymph node metastasis. Logistic regression demonstrated that depth of invasion, tumor size, and vascular tumor emboli were independently predictive factors for lymph node metastasis. The 5-year survival rate was 64.0%. Multivariate analysis showed that tumor size, tumor location, resection type, and pathological stage were independent prognostic factors. Based on tumor size, there were significant differences of 5-year survival between small size tumor (<6 cm) and large size tumor (≥6 cm) according to stage IIA (P = 0.006). Based on tumor location, there were significant differences of 5-year survival among different tumor location according to stage IB. Based on resection type, there were significant differences of overall 5-year survival between curative surgery and palliative surgery according to stage IIB (P = 0.015) and IIIA (P = 0.001).

Conclusion

Depth of invasion, tumor size, and vascular tumor emboli were independently predictive factors for lymph node metastasis. Tumor size, tumor location, resection type, and pathological stage were independent prognostic factors.     

Survivin和COX-2的表达及与胰腺癌预后的关系

目的:评价Survivin和COX-2在胰腺癌中的表达与预后的关系.方法:采用免疫组化二步法检测63例手术切除的原发性胰腺癌组织及11例癌旁非肿瘤胰腺组织中Survivin和COX-2的表达情况.应用spearman相关分析Survivin与COX-2表达的相关性.用Kaplan-Meier法分析生存曲线,多变量Cox比例风险回归模型筛选影响患者生存的独立预后因素.结果:Survivin、COX-2蛋白在胰腺腺癌中的表达呈正相关(r=0.613,P=0.000).Survivin阻性表达患者中位生存时间(9个月)明显小于阴性表达者中位生存时间(21个月),P=0.000; COX-2阳性表达患者中位生存时间(10个月)也明显小于阴性表达者生存时间(大于36个月),P=0.000; Survivin阴性/COX-2阴性组患者(9例)中位生存时间(大于36个月)及1年累计生存率为88.9％,均明显高于单一阳性表达或均阳性表达组.多因素分析(Cox模型)显示分化程度(P=0.002)、临床分期(P=0.000)及Survivin过表达(P=0.005)为影响胰腺癌预后的独立因素.结论:Survivin、COX-2蛋白在胰腺癌组织中表达上调且呈正相关,二者在胰腺癌的发生发展中可能具有协同作用,有望作为靶点用于胰腺癌的靶向治疗.患者的分化程度、临床分期及Survivin的表达水平是胰腺癌患者手术后生存的独立危险因素.     

Up-Regulation of 91H Promotes Tumor Metastasis and Predicts Poor Prognosis for Patients with Colorectal Cancer

Background

Long noncoding RNAs (lncRNAs) play widespread roles in gene regulation and cellular processes. However, the functional roles of lncRNAs in colorectal cancer (CRC) are not yet well elucidated. The aim of the present study was to measure the levels of lncRNA 91H expression in CRC and evaluate its clinical significance and biological roles in the development and progression of CRC.

Methods

91H expression and copy number variation (CNV) were measured in 72 CRC tumor tissues and adjacent normal tissues by real-time PCR. The biological roles of 91H were evaluated by MTT, scratch wound assay, migration and invasion assays, and flow cytometry.

Results

91H was significantly overexpressed in cancerous tissue and CRC cell lines compared with adjacent normal tissue and a normal human intestinal epithelial cell line. Moreover, 91H overexpression was closely associated with distant metastasis and poor prognosis in patients with CRC, except for CNV of 91H. Multivariate analysis indicated that 91H expression was an independent prognostic indicator, as well as distant metastasis. Our in vitro data indicated that knockdown of 91H inhibited the proliferation, migration, and invasiveness of CRC cells.

Conclusions

91H played an important role in the molecular etiology of CRC and might be regarded as a novel prognosis indicator in patients with CRC.     

Embryonic Morphogen Nodal Is Associated with Progression and Poor Prognosis of Hepatocellular Carcinoma

Background

Nodal, a TGF-β-related embryonic morphogen, is involved in multiple biologic processes. However, the expression of Nodal in hepatocellular carcinoma (HCC) and its correlation with tumor angiogenesis, epithelial-mesenchymal transition, and prognosis is unclear.

Methods

We used real-time PCR and Western blotting to investigate Nodal expression in 6 HCC cell lines and 1 normal liver cell line, 16 pairs of tumor and corresponding paracarcinomatous tissues from HCC patients. Immunohistochemistry was performed to examine Nodal expression in HCC and corresponding paracarcinomatous tissues from 96 patients. CD34 and Vimentin were only examined in HCC tissues of patients mentioned above. Nodal gene was silenced by shRNA in MHCC97H and HCCLM3 cell lines, and cell migration and invasion were detected. Statistical analyses were applied to evaluate the prognostic value and associations of Nodal expression with clinical parameters.

Results

Nodal expression was detected in HCC cell lines with high metastatic potential alone. Nodal expression is up-regulated in HCC tissues compared with paracarcinomatous and normal liver tissues. Nodal protein was expressed in 70 of the 96 (72.9%) HCC tumors, and was associated with vascular invasion (P = 0.000), status of metastasis (P = 0.004), AFP (P = 0.049), ICGR₁₅ (indocyanine green retention rate at 15 min) (P = 0.010) and tumor size (P = 0.000). High Nodal expression was positively correlated with high MVD (microvessal density) (P = 0.006), but not with Vimentin expression (P = 0.053). Significantly fewer migrated and invaded cells were seen in shRNA group compared with blank group and negative control group (P<0.05). High Nodal expression was found to be an independent factor for predicting overall survival of HCC.

Conclusions

Our study demonstrated that Nodal expression is associated with aggressive characteristics of HCC. Its aberrant expression may be a predictive factor of unfavorable prognosis for HCC after surgery.     

Podocalyxin Is a Marker of Poor Prognosis in Pancreatic Ductal Adenocarcinoma

Aim of the Study

Podocalyxin-like 1 is a transmembrane glyco-protein whose overexpression associates in many cancers with poor prognosis and unfavorable clinicopathological characteristics. Until now, its prognostic value has never been studied in pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate podocalyxin expression in PDAC by a novel monoclonal antibody and a commercially available polyclonal antibody.

Patients and Materials

With tissue microarrays and immuno-histochemistry, podocalyxin expression evaluation involved 168 PDAC patients. The associa-tions of the podocalyxin tumor expression with clinicopathological variables were explored by Fisher’s exact test and the linear-by-linear test. Survival analyses were by Kaplan-Meier anal-ysis and the Cox proportional hazard model.

Results

The polyclonal antibody revealed membranous podocalyxin expression in 73 (44.0%) specimens and the monoclonal antibody was highly expressed in 36 (21.8%) cases. Membranous expression by the polyclonal antibody was associated with T classification (p=0.045) and perineural invasion (p=0.005), and high expression by the mono-clonal antibody with poor differentiation (p=0.033). High podocalyxin expression associated significantly with higher risk of death from PDAC by both the polyclonal antibody (hazard ratio (HR) = 1.62; 95% confidence interval (CI) 1.12-2.33; p=0.01) and the monoclonal antibody (HR = 2.10, 95% CI 1.38-3.20; p<0.001). The results remained significant in multivariate analysis, adjusted for age, gender, stage, lymph node ratio (≥/< 20%), and perivascular invasion (respectively as HR = 2.03; 95% CI 1.32-3.13, p=0.001; and as HR = 2.36; 95% CI 1.47-3.80, p<0.001).

Conclusion

We found podocalyxin to be an independent factor for poor prognosis in PDAC. To our knowledge, this is the first such report of its prognostic value.     

YAP Promotes Ovarian Cancer Cell Tumorigenesis and Is Indicative of a Poor Prognosis for Ovarian Cancer Patients

YAP is a key component of the Hippo signaling pathway and plays a critical role in the development and progression of multiple cancer types, including ovarian cancer. However, the effects of YAP on ovarian cancer development in vivo and its downstream effectors remain uncertain. In this study we found that strong YAP expression was associated with poor ovarian cancer patient survival. Specifically, we showed for the first time that high YAP expression levels were positively correlated with TEAD4 gene expression, and their co-expression was a prognostic marker for poor ovarian cancer survival. Hyperactivation of YAP by mutating its five inhibitory phosphorylation sites (YAP-5SA) increased ovarian cancer cell proliferation, resistance to chemotherapeutic drugs, cell migration, and anchorage-independent growth. In contrast, expression of a dominant negative YAP mutant reversed these phenotypes in ovarian cancer cells both in vitro and in vivo. Our results suggested that YAP caused these effects by promoting an epithelial-to-mesenchymal transition. Thus, YAP promotes ovarian cancer cell growth and tumorigenesis both in vitro and in vivo. Further, high YAP and TEAD4 expression is a prognostic marker for ovarian cancer progression and a potential target for ovarian cancer treatment.     

VEGF—C、CD24在肺癌组织的表达及其与淋巴结转移及预后的关系

目的：探讨内皮生长因子一C（vascularendothelialgrowthfactor-C,VEGF-C）、黏附分子CD24在肺癌组织中的表达及其临床意义。方法：采用RT-PCR和免疫组化方法检测138例原发性肺癌患者肿瘤组织及癌旁组织中VEGF-C、CD24的表达水平。结果：肺癌组织中VEGF-C、CD24mRNA及蛋白的表达均高于癌旁组织（P〈0．05）,两者在肺癌组织中的表达明显正相关（P〈O．05）;有淋巴结转移组中vEGF-C、CD24mRNA及蛋白的阳性表达量均高于无淋巴结转移组（P〈0．05）;VEGF—C、CD24表达与淋巴结转移、肿瘤TNM分期等临床病理特征间有明显相关性（P〈0．05）;VEGF—C、CD24蛋白表达与IIIA期患者的短期预后有关,两者的mRNA水平与无病生存时间呈负相关。结论：VEGF-C、CD24在肺癌组织中均异常表达,可作为肺癌诊断的辅助标志物。     

The Expression of TMPRSS4 and Erk1 Correlates with Metastasis and Poor Prognosis in Chinese Patients with Gastric Cancer

Purpose

The present study investigated the clinical significance of transmembrane protease, serine 4(TMPRSS4) and extracellular signal-regulated kinases 1 (Erk1) in the development, progression and metastasis of gastric cancer.

Methods

Immunohistochemistry was employed to analyze TMPRSS4 and Erk1 expression in 436 gastric cancer cases and 92 non-cancerous human gastric tissues.

Results

Protein levels of TMPRSS4 and Erk1 were up-regulated in gastric cancer lesions compared with adjacent noncancerous tissues. High expression of TMPRSS4 correlated with age, size, Lauren’s classification, depth of invasion, lymph node and distant metastases, regional lymph node stage and TNM stage, and also with expression of Erk1. In stages I, II and III, the 5-year survival rate of patients with high TMPRSS4 expression was significantly lower than in patients with low expression. Further multivariate analysis suggests that up-regulation of TMPRSS4 and Erk1 were independent prognostic indicators for the disease, along with depth of invasion, lymph node and distant metastasis and TNM stage.

Conclusions

Expression of TMPRSS4 in gastric cancer is significantly associated with lymph node and distant metastasis, high Erk1 expression, and poor prognosis. TMPRSS4 and Erk1 proteins could be useful markers to predict tumor progression and prognosis of gastric cancer.     

High YKL-40 Serum Concentration Is Correlated with Prognosis of Chinese Patients with Breast Cancer

This study aimed to investigate the association between serum YKL-40 and prognosis of breast cancer in a Chinese population. Expression of YKL-40 of 120 Chinese patients with breast cancer and 30 controls (benign breast lesions) was measured in tumor tissue by immunohistochemistry and in serum by ELISA. Differences in YKL-40 positivity grouped by specific patients’ characteristics were compared using Pearson Chi-square test for rates of intratumoral staining, one-way ANOVA with a Bonferroni post-hoc comparison, or two-sample t-test for mean YKL-40 serum concentrations. Factors associated with overall survival were identified by univariate and multivariate cox-regression analyses. YKL-40 was elevated in approximately 75% of Chinese patients with breast cancer. A significantly higher percentage of patients with YKL-40 positive tumors had larger tumor size, higher TNM stage, and/or lymph node metastasis. Significantly higher mean YKL-40 serum concentrations were observed in patient subgroups with invasive lobular carcinoma (P<0.0167), higher TNM stage (P<0.001), and positive lymph node metastasis (P<0.001). The estimated mean survival time of patients with YKL-40 positive tumors was significantly shorter than for patients with YKL-40 negative tumors (55.13 months vs 65.78 months, P = 0.017). Multivariable Cox-regression analysis identified a significant association of overall survival time with YKL-40 serum concentration. Patients with YKL-40 positive tumors had significantly shorter disease free survival times than those with YKL-40 negative tumors. We propose that the potential utility of YKL-40 intratumoral staining or serum concentration as a biomarker for breast cancer is greatest within 5 years of diagnosis.     

二次肿瘤细胞减灭术在铂类敏感的复发性卵巢上皮癌中的作用

目的:探讨二次肿瘤细胞减灭术对铂类敏感的复发性卵巢上皮癌治疗的临床意义。方法:回顾性分析我院于2002年1月至2012年12月收治的115例铂类敏感的复发性卵巢上皮癌患者的临床及随访资料。结果:在115例铂类敏感的复发性卵巢上皮癌中,66例接受了二次肿瘤细胞减灭术(手术组),术后辅以铂类为基础的化疗。49例患者只接受了以铂类为基础的化疗(对照组)。两组患者肿瘤病理分型无统计学差异(P=0.485)。与对照组相比,手术组FIGO分期IV期患者的比例少(15.2%VS 34.7%,P=0.014),低分化患者的比例少(71.2%VS 91.8%,P=0.024),多发复发病灶患者的比例少(28.3%VS 49.0%,P=0.027)。平均随访30.2个月(6-48个月),Kaplan-Meier生存分析显示,手术组与对照组患者的中位生存期分别为35.0个月和27.0个月,差异有统计学差异(Log rank 7.9,P=0.005)。多因素Cox回归分析显示,校正了年龄、肿瘤病理类型、病理分级及FIGO分期后,不同治疗方案是复发上皮性卵巢癌患者远期生存率的独立影响因素。结论:二次肿瘤细胞减灭术可以改善铂类敏感的复发性卵巢上皮癌患者的临床预后。     

Expression of c-fos Was Associated with Clinicopathologic Characteristics and Prognosis in Pancreatic Cancer

It has long been regarded that pancreatic cancer (PC) is a life-threatening malignant tumor. Thus, much attention has been paid for factors, especially relative molecules, predictive for prognosis of PC. However, c-fos expression in PC was less investigated. In addition, its association with clinicopathologic variables and prognosis remains unknown. In the present study, expression of c-fos was detected by tissue microarray-based immunohistochemical staining in cancer and adjacent tissues from 333 patients with PC. The staining results were correlated with clinicopathologic parameters and overall survival. Furthermore, prognostic significance of c-fos in subsets of PC was also evaluated. It was shown that low expression of c-fos was more often in cancer than in adjacent tissues of PC (P<0.001). Besides, high cancerous c-fos expression was significantly associated with tumor site and T stage, whereas peri-neural invasion was of a borderline significant relevance. Log-rank test revealed that high expression of c-fos in cancer tissues was a significant marker of poor overall survival, accompanied by some conventional clinicopathologic variables, such as sex, grade, peri-neural invasion, T and N stages. More importantly, cancerous c-fos expression was identified as an independent prognosticator in multivariate analysis. Finally, the prognostic implication of c-fos expression was proven in four subsets of patients with PC. These data suggested that c-fos expression was of relationships with progression and dismal prognosis of PC.     

Expression of Sirtuin 1 and 2 Is Associated with Poor Prognosis in Non-Small Cell Lung Cancer Patients

Background

Sirtuin 1 (SIRT1) and sirtuin 2 (SIRT2) are NAD+-dependent protein deacetylases involved in the regulation of key cancer-associated genes. In this study we evaluated the relevance of these deacetylases in lung cancer biology.

Material and Methods

Protein levels of SIRT1 and SIRT2 were determined in non-small cell lung cancer (NSCLC) cell lines and primary tumors from 105 patients. Changes in proliferation were assessed after SIRT1 and SIRT2 downregulation in lung cancer cell lines using siRNA-mediated technology or tenovin-1, a SIRT1 and SIRT2 inhibitor.

Results

High SIRT1 and SIRT2 protein levels were found in NSCLC cell lines compared with non-tumor lung epithelial cells. The expression of SIRT1 and SIRT2 proteins was also significantly higher in lung primary tumors than in normal tissue (P<0.001 for both sirtuins). Stronger nuclear SIRT1 staining was observed in adenocarcinomas than in squamous cell carcinomas (P=0.033). Interestingly, in NSCLC patients, high SIRT1 and SIRT2 expression levels were associated with shorter recurrence-free survival (P=0.04 and P=0.007, respectively). Moreover, the combination of high SIRT1 and SIRT2 expression was an independent prognostic factor for shorter recurrence-free survival (P=0.002) and overall survival (P=0.022). In vitro studies showed that SIRT1 and/or SIRT2 downregulation significantly decreased proliferation of NSCLC.

Conclusions

Our results support the hypothesis that SIRT1 and SIRT2 have a protumorigenic role in lung cancer, promoting cell proliferation. Moreover, the expression of these proteins is associated with poor prognosis in NSCLC patients and may help to identify those NSCLC patients with high risk of recurrence that could benefit from adjuvant therapy after resection.     

Serum YKL-40 Level Is Associated with the Chemotherapy Response and Prognosis of Patients with Small Cell Lung Cancer

This study was to explore the association between the serum YKL-40 level and the clinical characteristics, the response to chemotherapy and prognosis in small cell lung cancer (SCLC). Serum YKL-40 levels were detected and compared in 120 patients with SCLC pre- and post-chemotherapy, and in 40 healthy controls. Receiver operating characteristics (ROC) curves were adopted for diagnosis and calculation of area under ROC curve in SCLC. The Kaplan–Meier method, univariate and multivariate Cox regression analysis were used to analyze the correlation between pre-chemotherapy serum YKL-40 levels and progression-free survival (PFS) and overall survival (OS). The pre-chemotherapy serum YKL-40 levels were significantly higher than those of the controls (p<0.001). The post-chemotherapy serum YKL-40 levels in the SCLC cases were lower than pre-chemotherapy serum YKL-40 levels in these cases (p = 0.026). The patients with high serum YKL-40 showed a poorer response to chemotherapy than those patients with low serumYKL-40 (p = 0.031). Univariate analysis revealed that SCLC patients with high serum YKL-40 had a shorter PFS and OS than those with low serum YKL-40 (HR of 1.74, p = 0.033; HR of 1.33, p = 0.001). Cox multivariate analysis indicated that YKL-40 was an independent prognostic indicator of PFS and OS (HR of 1.12, p = 0.029; HR of 1.84, p = 0.025). Kaplan–Meier survival curves further confirmed that patients with low serum YKL-40 have longer PFS and OS (p = 0.016 and p = 0.041, respectively). These results suggest that YKL-40 is a potential prognostic marker of chemotherapy response in SCLC.