遲新楠
[摘要] 目的 探究血清鈣在子宮內(nèi)膜癌患者血清中的表達(dá)及臨床意義。方法 回顧性選擇2019年1—12月遼寧省錦州市中心醫(yī)院收治的100例子宮內(nèi)膜癌患者為研究組,另選取同期50例子宮內(nèi)膜良性病變患者為病例對(duì)照組,選取50名體檢健康者為對(duì)照組,對(duì)比3組個(gè)體的血清鈣及腫瘤標(biāo)志物糖類抗原12-5(CA12-5)、糖類抗原19-9(CA19-9)水平差異,分析上述指標(biāo)相關(guān)性,繪制血清鈣對(duì)子宮內(nèi)膜癌患者診斷ROC曲線,并初步探究不同結(jié)局子宮內(nèi)膜癌患者血清鈣水平差異。結(jié)果 ①研究組患者的血清鈣水平明顯低于病例對(duì)照組和對(duì)照組,CA12-5和CA19-9水平明顯高于病例對(duì)照組與對(duì)照組(P<0.05);②子宮內(nèi)膜癌患者血清鈣水平同CA12-5和CA19-9水平均呈現(xiàn)明顯的負(fù)相關(guān)性(r=-0.5460,r=-0.5539,P<0.05);③以血清Ca2+水平≥2.32 mmol/L為截?cái)帱c(diǎn),繪制血清鈣對(duì)子宮內(nèi)膜癌的診斷ROC曲線,計(jì)算其AUC為0.7175(95% CI=0.5407~0.8943,P=0.0186);④隨訪18個(gè)月,子宮內(nèi)膜癌死亡組患者的血清鈣水平明顯低于存活組,腫瘤標(biāo)志物水平明顯高于存活組(P<0.05)。結(jié)論 血清鈣在子宮內(nèi)膜癌患者體內(nèi)呈現(xiàn)明顯的異常低表達(dá)態(tài),可考慮將其作為子宮內(nèi)膜癌診斷及預(yù)后分析的參考指標(biāo)應(yīng)用于臨床。
[關(guān)鍵詞] 血清鈣;子宮內(nèi)膜癌;表達(dá)水平;診斷價(jià)值;預(yù)后分析
[中圖分類號(hào)] R737.33? ? ? ? ? [文獻(xiàn)標(biāo)識(shí)碼] A? ? ? ? ? [文章編號(hào)] 1673-9701(2022)14-0009-03
Expression and significance of serum calcium in serum of patients with endometrial cancer
CHI Xinnan
Department of Oncology, Jinzhou Central Hospital in Liaoning Province, Jinzhou? 121000, China
[Abstract] Objective To investigate the expression and clinical significance of serum calcium in the serum of patients with endometrial cancer. Methods A total of 100 patients with endometrial cancer treated in Jinzhou Central Hospital in Liaoning Province from January to December 2019 were retrospectively selected as the study group, and another 50 patients with benign endometrial lesions during the same period were selected as the case-control group, and 50 healthy individuals received physical examination were selected as the control group. The levels of serum calcium and tumor markers carbohydrate antigen 12-5 (CA12-5) and carbohydrate antigen 19-9 (CA19-9) were compared among the three groups, to analyze the correlation between the above indexes, plot the ROC curve of serum calcium for diagnosis of endometrial cancer, and initially investigate the differences of serum calcium levels among endometrial cancer patients with different outcomes. Results ①I(mǎi)n the study group, the serum calcium level was significantly lower than those in the case-control group and the control group, and the levels of CA12-5 and CA19-9 were significantly higher than those in the case-control group and the control group (P<0.05). ②The serum calcium levels in the patients with endometrial cancer were significantly negatively correlated with the levels of CA12-5 and CA19-9 (r=-0.5460, r=-0.5539, P<0.05). ③Using the serum Ca2+level≥2.32 mmol/L as the cutoff point, the ROC curve of serum calcium for the diagnosis of endometrial cancer was drawn, and the AUC was calculated as 0.7175 (95% CI=0.5407-0.8943, P=0.0186). ④At 18 months of follow-up, the serum calcium levels of the patients who died of endometrial cancer were significantly lower than those of the patients who survived, and the tumor marker levels were significantly higher than those of the patients who survived (P<0.05). Conclusion Serum calcium presents a significant abnormally low expression status in patients with endometrial cancer. It can be considered as a reference index in the diagnosis and prognosis analysis of endometrial cancer in clinical practice.DDC37891-CE87-47D1-9684-E3D4034F4D14
[Key words] Serum calcium; Endometrial cancer; Expression level; Diagnostic value; Prognostic analysis
子宮內(nèi)膜癌是一種原發(fā)于子宮內(nèi)膜的上皮性惡性腫瘤,其中以子宮內(nèi)膜腺體的腺癌最為常見(jiàn)[1]。流調(diào)學(xué)顯示,子宮內(nèi)膜癌約占女性全身惡性腫瘤的7%,女性生殖道惡性腫瘤的20%-30%,絕經(jīng)后的中老年女性為該病的高發(fā)群體[2-3]。當(dāng)前子宮內(nèi)膜癌的發(fā)病機(jī)制尚不清晰,有研究指出Ⅰ、Ⅱ期子宮內(nèi)膜癌患者外科手術(shù)聯(lián)合放療干預(yù)后,5年生存率高達(dá)88.1%,但Ⅲ期和Ⅳ期患者干預(yù)后的5年生存率僅為35.65%,且復(fù)發(fā)患者往往預(yù)后較差[4],因此,子宮內(nèi)膜癌的先期診斷及臨床干預(yù)對(duì)改善其預(yù)后具有重要意義。鈣是人體內(nèi)含量最多的陽(yáng)離子,正常成年人含鈣25~30 mol,鈣離子在維持正常神經(jīng)肌肉應(yīng)激性、腺體分泌及一些酶系統(tǒng)的活性方面發(fā)揮重要作用,近些年有研究發(fā)現(xiàn),鈣離子在多種惡性腫瘤患者中均呈低表達(dá)態(tài)[5-6],本研究以100例子宮內(nèi)膜癌患者為調(diào)研對(duì)象,分析血清鈣在患者血清中的表達(dá)意義,以期為子宮內(nèi)膜癌的早期診斷提供參考,現(xiàn)報(bào)道如下。
1 資料與方法
1.1 一般資料
回顧性選擇2019年1—12月遼寧省錦州市中心醫(yī)院收治的100例子宮內(nèi)膜癌患者為研究組,另?yè)袢⊥?0例子宮內(nèi)膜良性病變患者為病例對(duì)照組,擇取50例體檢健康者為對(duì)照組。納入標(biāo)準(zhǔn):①研究組患者均經(jīng)宮腔鏡刮宮病理取材確診為子宮內(nèi)膜癌[7];②意識(shí)清晰;能配合進(jìn)行調(diào)研;③調(diào)研報(bào)經(jīng)醫(yī)院醫(yī)學(xué)倫理委員會(huì)批準(zhǔn)實(shí)施;④臨床資料及隨訪資料完整;⑤患者簽署知情同意書(shū)。排除標(biāo)準(zhǔn):①并發(fā)精神疾病者;②并發(fā)心、肝、肺、腎等功能異常者;③并發(fā)血液系統(tǒng)疾患者;④并發(fā)免疫系統(tǒng)疾病者;⑤并發(fā)急慢性感染者;⑥并發(fā)其他部位腫瘤者;⑦藥物或酒精依賴者。三組個(gè)體的基線臨床資料比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05),具有可比性。見(jiàn)表1。
1.2 方法
采集三組個(gè)體的清晨空腹靜脈血樣,肝素抗凝后離心留血清備用,置于-80℃條件下待樣本采集完畢后統(tǒng)一送檢,血清鈣水平的檢測(cè)依托AU5800全自動(dòng)生化分析儀(貝克曼庫(kù)爾特)展開(kāi),腫瘤標(biāo)志物CA12-5和CA19-9檢測(cè)采用電化學(xué)發(fā)光法(羅氏公司電化學(xué)發(fā)光免疫分析儀及其配套試劑)展開(kāi),上述操作均嚴(yán)格按照試劑盒說(shuō)明書(shū)進(jìn)行。
1.3 觀察指標(biāo)及評(píng)測(cè)標(biāo)準(zhǔn)
①就三組個(gè)體的血清鈣、CA12-5、CA19-9水平進(jìn)行組間比較。②就子宮內(nèi)膜癌患者血清鈣、CA12-5、CA19-9水平相關(guān)性進(jìn)行分析。③繪制血清鈣對(duì)子宮內(nèi)膜癌診斷ROC曲線。④對(duì)100例子宮內(nèi)膜癌患者開(kāi)展為期18個(gè)月的臨床隨訪,將其按照臨床結(jié)局分為死亡組(7例)和存活組(93例),對(duì)比兩組血清鈣、CA12-5和CA19-9水平差異。正常成年人血清鈣水平為(2.03~2.54) mmol/L,CA12-5常值為(0~35) U/ml,CA19-9常值為(0~37) U/ml[8]。
1.4 統(tǒng)計(jì)學(xué)方法
將采集的數(shù)據(jù)錄入到EXCEL表格中,使用SPSS 22.0統(tǒng)計(jì)學(xué)軟件進(jìn)行數(shù)據(jù)分析,對(duì)采集數(shù)據(jù)開(kāi)展正態(tài)分布檢驗(yàn),計(jì)量資料以均數(shù)±標(biāo)準(zhǔn)差(x±s)表示,三組間的差異分析行單因素方差分析,兩組間的差異性分析行t檢驗(yàn),相關(guān)性分析使用pearson相關(guān)系數(shù)進(jìn)行分析,P<0.05為差異有統(tǒng)計(jì)學(xué)意義。
2 結(jié)果
2.1 不同組別個(gè)體血清鈣及腫瘤標(biāo)記物水平差異
研究組患者的血清鈣水平明顯低于病例對(duì)照組和對(duì)照組,CA12-5和CA19-9水平明顯高于病例對(duì)照組與對(duì)照組,上述指標(biāo)組間兩兩比較,差異均有統(tǒng)計(jì)學(xué)意義(P<0.05)。見(jiàn)表2。
2.2 子宮內(nèi)膜癌患者血清鈣與腫瘤標(biāo)志物水平相關(guān)性分析
對(duì)子宮內(nèi)膜癌患者血清鈣水平與CA12-5和CA19-9水平開(kāi)展相關(guān)性分析,結(jié)果顯示,血清鈣水平同CA12-5和CA19-9水平均呈現(xiàn)明顯的負(fù)相關(guān)性(r=-0.5460,r=-0.5539,P<0.05)。見(jiàn)圖1。
2.3 血清鈣對(duì)子宮內(nèi)膜癌診斷價(jià)值分析
以病理檢測(cè)結(jié)果為金標(biāo)準(zhǔn),以血清Ca2+水平≥2.32 mmol/L為截?cái)帱c(diǎn),繪制血清鈣對(duì)子宮內(nèi)膜癌的診斷ROC曲線,計(jì)算其AUC為0.7175(95% CI=0.5407~0.8943,P=0.0186)。見(jiàn)圖2。
2.4 評(píng)估不同結(jié)局子宮內(nèi)膜癌患者血清鈣及腫瘤標(biāo)志物水平差異
對(duì)入組患者開(kāi)展為期18個(gè)月的隨訪,將100例子宮內(nèi)膜癌患者按照臨床結(jié)局分為死亡組(7例)和存活組(93例),對(duì)比兩組患者血清鈣及腫瘤標(biāo)志物的水平差異,結(jié)果顯示死亡組患者的血清鈣水平明顯低于存活組,腫瘤標(biāo)志物(CA12-5、CA19-9)水平明顯高于存活組(P<0.05)。見(jiàn)表3。
3 討論
宮頸癌、子宮內(nèi)膜癌、卵巢癌合稱為女性生殖道三大惡性腫瘤,數(shù)據(jù)顯示,美國(guó)子宮內(nèi)膜癌發(fā)病率位居?jì)D科惡性腫瘤之首。我國(guó)子宮內(nèi)膜癌發(fā)病率僅次于宮頸癌,子宮內(nèi)膜癌又名子宮體癌,好發(fā)于子宮體的內(nèi)膜,主要表現(xiàn)形式為內(nèi)膜腺癌,故而又被稱為子宮內(nèi)膜癌[9-10]。近些年子宮內(nèi)膜癌發(fā)病率呈現(xiàn)逐漸升高趨勢(shì),在北美和歐洲地區(qū)已躍居女性生殖惡性腫瘤發(fā)病率首位,對(duì)女性的生命健康造成嚴(yán)重威脅[11]。該病進(jìn)展較慢,治療難度小,且轉(zhuǎn)移較慢,故而其預(yù)后相對(duì)較好,患者5年生存率一般達(dá)80%以上[12]。近年來(lái)隨著我國(guó)居民生活方式及飲食結(jié)構(gòu)的調(diào)整,子宮內(nèi)膜癌的發(fā)病率有逐年遞增趨勢(shì)[13],尤其是青年女性,如得不到及時(shí)治療可能會(huì)對(duì)其生育造成影響,因而尋求一種子宮內(nèi)膜癌的早期診斷鑒別措施對(duì)改善患者預(yù)后具有重要意義。DDC37891-CE87-47D1-9684-E3D4034F4D14
本研究通過(guò)設(shè)立對(duì)照分組的方式,就血清鈣在子宮內(nèi)膜癌患者血清中的表達(dá)意義進(jìn)行分析,結(jié)果顯示,相較于健康對(duì)照組及良性病變的病例對(duì)照組患者,子宮內(nèi)膜癌患者的血清鈣水平明顯更低,但CA12-5和CA19-9水平明顯更高,組間差異有統(tǒng)計(jì)學(xué)意義(P<0.05),這與相關(guān)研究結(jié)果類似。但一項(xiàng)研究通過(guò)將56例甲狀腺癌患者與60例健康體檢者進(jìn)行比較發(fā)現(xiàn),甲狀腺癌患者血清鈣離子水平與健康對(duì)照個(gè)體差異明顯,進(jìn)一步開(kāi)展logistic分析發(fā)現(xiàn)鈣離子水平還會(huì)對(duì)甲狀腺癌發(fā)生風(fēng)險(xiǎn)產(chǎn)生影響[9]。本研究組認(rèn)為,血清鈣在多種腫瘤患者體內(nèi)呈現(xiàn)低表達(dá)態(tài)已被多個(gè)研究證實(shí)[14-15],其原因可能與鈣離子能參與機(jī)體代謝,而腫瘤會(huì)影響個(gè)體代謝有關(guān)。以肺癌為例,肺癌患者會(huì)分泌含有降鈣素的異位激素,從而抑制破骨細(xì)胞生成,導(dǎo)致鈣鹽沉積于骨骼中,造成血鈣水平下降。此外還有研究認(rèn)為,多數(shù)腫瘤會(huì)對(duì)患者的肝腎功能造成一定程度的損傷,造成維生素D無(wú)法正常轉(zhuǎn)化為活性維生素D,進(jìn)而導(dǎo)致血鈣水平降低[16]。
本研究進(jìn)一步通過(guò)相關(guān)性分析發(fā)現(xiàn),血清鈣水平與腫瘤標(biāo)志物CA12-5、CA19-9水平呈現(xiàn)明顯相關(guān)性,而上述兩種標(biāo)志物已被證實(shí)在腫瘤的鑒別診斷中具有較高的應(yīng)用價(jià)值,因而可推測(cè)血清鈣也可應(yīng)用于子宮內(nèi)膜癌的診斷鑒別。為驗(yàn)證該理論的可行性,本研究繪制血清鈣對(duì)子宮內(nèi)膜癌的診斷ROC曲線,結(jié)果顯示其AUC為0.7175,提示診斷價(jià)值較好,這為子宮內(nèi)膜癌的臨床鑒別提供了新的思路。最后通過(guò)對(duì)100例子宮內(nèi)膜癌患者開(kāi)展為期18個(gè)月的隨訪并對(duì)比發(fā)現(xiàn),死亡組子宮內(nèi)膜癌患者的血清鈣水平明顯低于存活組,CA12-5和CA19-9水平明顯高于存活組,這提示血清鈣可能對(duì)預(yù)測(cè)子宮內(nèi)膜癌患者的預(yù)后也具有一定的應(yīng)用價(jià)值,但仍需進(jìn)一步的數(shù)據(jù)進(jìn)行驗(yàn)證。
綜上所述,血清鈣在子宮內(nèi)膜癌患者體內(nèi)呈現(xiàn)明顯的異常低表達(dá)態(tài),可考慮將其作為子宮內(nèi)膜癌診斷及預(yù)后分析的參考指標(biāo)應(yīng)用于臨床。
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(收稿日期:2021-10-14)DDC37891-CE87-47D1-9684-E3D4034F4D14